Felipe Villegas-carlos - Academia.edu (original) (raw)
Papers by Felipe Villegas-carlos
Molecular Oncology, Feb 9, 2019
Triple negative breast cancer (TNBC) represents an aggressive phenotype with poor prognosis compa... more Triple negative breast cancer (TNBC) represents an aggressive phenotype with poor prognosis compared with ER, PR, and HER2-positive tumors. TNBC is a heterogeneous disease, and gene expression analysis has identified seven molecular subtypes. Accumulating evidence demonstrates that long non-coding RNA (lncRNA) are involved in regulation of gene expression and cancer biology, contributing to essential cancer cell functions. In this study, we analyzed the expression profile of lncRNA in TNBC subtypes from 156 TNBC samples, and then characterized the functional role of LncKLHDC7B (ENSG00000226738). A total of 710 lncRNA were found to be differentially expressed between TNBC subtypes, and a subset of these altered lncRNA were independently validated. We discovered that LncKLHDC7B (ENSG00000226738) acts as a transcriptional modulator of its neighboring coding gene KLHDC7B in the immunomodulatory subtype. Furthermore, LncKLHDC7B knockdown enhanced migration and invasion, and promoted resistance to cellular death. Our findings confirmed the contribution of LncKLHDC7B to induction of apoptosis and inhibition of cell Abbreviations ADAM9, ADAM metallopeptidase domain 9; AMOT, angiomotin; APP, amyloid beta precursor protein;
Cirugía y cirujanos, May 1, 2015
Background: Breast cancer is the leading oncological cause of death in Mexican women over 25 year... more Background: Breast cancer is the leading oncological cause of death in Mexican women over 25 years old. Given the need to improve postoperative cosmetic results in patients with breast cancer, oncoplastic surgery has been developed, which allows larger tumour resections and minor cosmetic alterations. Objective: To determine the oncological feasibility and cosmetic outcome of oncoplastic surgery at the Instituto de Enfermedades de la Mama, FUCAM, AC. Material and methods: A review was conducted from January 2010 to July 2013, which included patients with breast cancer diagnosis treated with conventional breast-conserving surgery or with oncoplastic surgery in the Instituto de Enfermedades de la Mama, FUCAM AC. Clinical and histopathological parameters were compared between the two groups, and a questionnaire of cosmetic satisfaction and quality of life was applied. Results: Of the 171 patients included, 95 of them were treated with conventional breastconserving surgery and 76 with oncoplastic surgery. Pathological tumour size was significantly larger in patients treated with oncoplastic surgery (p = 0.002). There were no differences found between the groups as regards the number of patients with positive surgical margin, the rate of complications, and cosmetic satisfaction. Conclusion: This study demonstrates the oncological feasibility and high cosmetic satisfaction of oncoplastic surgery with minimal psycho-social impact on patients.
Scientific Reports, 2020
Breast cancer (BRCA) is a serious public health problem, as it is the most frequent malignant tum... more Breast cancer (BRCA) is a serious public health problem, as it is the most frequent malignant tumor in women worldwide. BRCA is a molecularly heterogenic disease, particularly at gene expression (mRNAs) level. Recent evidence shows that coding RNAs represent only 34% of the total transcriptome in a human cell. The rest of the 66% of RNAs are non-coding, so we might be missing relevant biological, clinical or regulatory information. In this report, we identified nine novel tumor types from TCGA with FAM83H-AS1 deregulation. We used survival analysis to demonstrate that FAM83H-AS1 expression is a marker for poor survival in IHC-detected ER and PR positive BRCA patients and found a significant correlation between FAM83H-AS1 overexpression and tamoxifen resistance. Estrogen and Progesterone receptor expression levels interact with FAM83H-AS1 to potentiate its effect in OS prediction. FAM83H-AS1 silencing impairs two important breast cancer related pathways: cell migration and cell death...
Cancer Epidemiology, Biomarkers & Prevention, 2020
Breast cancer is a relevant public health problem that affects millions of women worldwide. Breas... more Breast cancer is a relevant public health problem that affects millions of women worldwide. Breast tumors are recognized as a clinically and molecular heterogeneous pathology, but the genomic basis of its variability remains poorly understood, mainly regarding the comprehensive of ethnicity/racial disparities and their consequences in genomics studies. Moreover, most of the comprehensive molecular characterizations are predominantly centered on Caucasian population. Thus, we deeply characterized the molecular architecture of breast cancer in a set of Mexican patients through genomic and transcriptomic portraits. We explored the molecular features of breast cancers in Mexican-Hispanic (HM) women and compared them with public multi-ethnic datasets. HM patients presented an earlier onset of the disease, in particular in the aggressive Basal-like/triple negative and Luminal B subtypes. The significant E17K hotspot mutation in AKT1 gene occurred in 8% of the HM tumors, an enriched preval...
Nature Communications, 2021
Breast cancer is a heterogeneous pathology, but the genomic basis of its variability remains poor... more Breast cancer is a heterogeneous pathology, but the genomic basis of its variability remains poorly understood in populations other than Caucasians. Here, through DNA and RNA portraits we explored the molecular features of breast cancers in a set of Hispanic-Mexican (HM) women and compared them to public multi-ancestry datasets. HM patients present an earlier onset of the disease, particularly in aggressive clinical subtypes, compared to non-Hispanic women. The age-related COSMIC signature 1 was more frequent in HM women than in those from other ancestries. We found the AKT1E17K hotspot mutation in 8% of the HM women and identify the AKT1/PIK3CA axis as a potentially druggable target. Also, HM luminal breast tumors present an enhanced immunogenic phenotype compared to Asiatic and Caucasian tumors. This study is an initial effort to include patients from Hispanic populations in the research of breast cancer etiology and biology to further understand breast cancer disparities.
Frontiers in Oncology, 2021
Breast cancer (BRCA) is a serious public health problem, as it is the most frequent malignant tum... more Breast cancer (BRCA) is a serious public health problem, as it is the most frequent malignant tumor in women worldwide. BRCA is a molecularly heterogeneous disease, particularly at gene expression (mRNAs) level. Recent evidence shows that coding RNAs represent only 34% of the total transcriptome in a human cell. The rest of the 66% of RNAs are non−coding, so we might be missing relevant biological, clinical or regulatory information. In this report, we identified two novel tumor types from TCGA with LINC00460 deregulation. We used survival analysis to demonstrate that LINC00460 expression is a marker for poor overall (OS), relapse-free (RFS) and distant metastasis-free survival (DMFS) in basal-like BRCA patients. LINC00460 expression is a potential marker for aggressive phenotypes in distinct tumors, including HPV-negative HNSC, stage IV KIRC, locally advanced lung cancer and basal-like BRCA. We show that the LINC00460 prognostic expression effect is tissue-specific, since its upreg...
Scientific Reports, 2020
Breast cancer is the most commonly diagnosed neoplasm in women worldwide with a well-recognized h... more Breast cancer is the most commonly diagnosed neoplasm in women worldwide with a well-recognized heterogeneous pathology, classified into four molecular subtypes: Luminal A, Luminal B, HER2-enriched and Basal-like, each one with different biological and clinical characteristics. Long non-coding RNAs (lncRNAs) represent 33% of the human transcriptome and play critical roles in breast carcinogenesis, but most of their functions are still unknown. Therefore, cancer research could benefit from continued exploration into the biology of lncRNAs in this neoplasm. We characterized lncRNA expression portraits in 74 breast tumors belonging to the four molecular subtypes using transcriptome microarrays. To infer the biological role of the deregulated lncRNAs in the molecular subtypes, we performed co-expression analysis of lncRNA–mRNA and gene ontology analysis. We identified 307 deregulated lncRNAs in tumor compared to normal tissue and 354 deregulated lncRNAs among the different molecular sub...
Frontiers in Oncology, 2020
Studies have suggested a potential role of somatic mitochondrial mutations in cancer development.... more Studies have suggested a potential role of somatic mitochondrial mutations in cancer development. To analyze the landscape of somatic mitochondrial mutation in breast cancer and to determine whether mitochondrial DNA (mtDNA) mutational burden is correlated with overall survival (OS), we sequenced whole mtDNA from 92 matchedpaired primary breast tumors and peripheral blood. A total of 324 germline variants and 173 somatic mutations were found in the tumors. The most common germline allele was 663G (12S), showing lower heteroplasmy levels in peripheral blood lymphocytes than in their matched tumors, even reaching homoplasmic status in several cases. The heteroplasmy load was higher in tumors than in their paired normal tissues. Somatic mtDNA mutations were found in 73.9% of breast tumors; 59% of these mutations were located in the coding region (66.7% non-synonymous and 33.3% synonymous). Although the CO1 gene presented the highest number of mutations, tRNA genes (T, C, and W), rRNA 12S, and CO1 and ATP6 exhibited the highest mutation rates. No specific mtDNA mutational profile was associated with molecular subtypes of breast cancer, and we found no correlation between mtDNA mutational burden and OS. Future investigations will provide insight into the molecular mechanisms through which mtDNA mutations and heteroplasmy shifting contribute to breast cancer development.
Human Genomics, 2019
Interpretation of variants of unknown significance (VUS) in genetic tests is complicated in ethni... more Interpretation of variants of unknown significance (VUS) in genetic tests is complicated in ethnically diverse populations, given the lack of information regarding the common spectrum of genetic variation in clinically relevant genes. Public availability of data obtained from high-throughput genotyping and/or exome massive parallel sequencing (MPS)-based projects from several thousands of outbred samples might become useful tools to evaluate the pathogenicity of a VUS, based on its frequency in different populations. In the case of the Mexican and other Latino populations, several thousands of samples have been genotyped or sequenced during the last few years as part of different efforts to identify common variants associated to common diseases. In this report, we analyzed Mexican population data from a sample of 3985 outbred individuals, and additional 66 hereditary breast cancer patients were analyzed in order to better define the spectrum of common genomic variation of the BRCA1 and BRCA2 genes. Our analyses identified the most common genetic variants in these clinically relevant genes as well as the presence and frequency of specific pathogenic mutations present in the Mexican population. Analysis of the 3985 population samples by MPS identified three pathogenic mutations in BRCA1, only one population sample showed a BRCA1 exon 16-17 deletion by MLPA. This resulted in a basal prevalence of deleterious mutations of 0.10% (1:996) for BRCA1 and 11 pathogenic mutations in BRCA2, resulting in a basal prevalence of deleterious mutations of 0.276% (1:362) for BRCA2, combined of 0.376% (1:265). Separate analysis of the breast cancer patients identified the presence of pathogenic mutations in 18% (12 pathogenic mutations in 66 patients) of the samples by MPS and 13 additional alterations by MLPA. These results will support a better interpretation of clinical studies focused on the detection of BRCA mutations in Mexican and Latino populations and will help to define the general prevalence of deleterious mutations within these populations.
Cancer Research, 2019
BACKGROUND: Advances in chemotherapy and target therapy have made treatment of breast cancer (BC)... more BACKGROUND: Advances in chemotherapy and target therapy have made treatment of breast cancer (BC) more effective; however, survivors of BC suffer an increased burden of cardiotoxicity. The aim of this study is to determine the risk factors in a Mexican patients (pt) METHODS:Observational study of a cohort of pt with locally BC and Her2 (+++) treated with trastuzumab (TZ). According to clinical stage, they underwent to surgery or neoadjuvant chemotherapy, scheme was at the decision of the physician. The main schemes: AC-T, EC-T, FAC-T, FEC-T, Paclitaxel, intravenous (IV) or subcutaneous TZ. The doses were according to NCCN guidelines and the route of administration of TZ was decision of the oncologist. Ventriculography was performed basally, at 4,8,12 cycles and at the end of treatment. If the pt presented a decrease in the ejection fraction>10% with/without symptoms, they received cardioprotection (metoprolol+atorvastatin). It was the oncologist decision to suspend chemotherapy a...
Cirugía y cirujanos
Thoracic trauma accounts for 25% of deaths due to trauma. Chest trauma patients generally present... more Thoracic trauma accounts for 25% of deaths due to trauma. Chest trauma patients generally present to the emergency room with pneumo- or hemothorax. According to the majority of the studies, management of closed thoracostomy for trauma includes the use of antimicrobial drugs to prevent infectious complications, but this has not been proven to be beneficial. We undertook this study to evaluate antimicrobial use in thoracic trauma patients with closed thoracostomy and its impact on the development of infectious complications. We carried out a prospective, randomized, double blind, comparative study. Patients with isolated chest trauma requiring closed thoracostomy were divided into two groups. Group A received cefalotin, and group B received placebo. Ages ranged from 15-65 years. Results were analyzed with chi(2) and Fisher exact test. One hundred twenty six patients were included in this study. There were 63 patients in each group with similar demographic characteristics. The mean len...
Revista Mexicana de Mastología, 2019
Revista Mexicana de Mastología, 2020
El carcinoma metaplásico de células escamosas de mama representa menos del 1% de todos los carcin... more El carcinoma metaplásico de células escamosas de mama representa menos del 1% de todos los carcinomas de mama invasores. Reporte de caso: Mujer de 47 años con carcinoma metaplásico con diferenciación epidermoide. Inmunohistoquímica con receptores de estrógeno 30%, receptores de progesterona 5%, Her2 negativo, Ki 67 80%. Se realiza mastectomía de limpieza con resección amplia de piel y cobertura cutánea con colgajo dorsal. Estudio histopatológico definitivo: carcinoma metaplásico con diferenciación epidermoide de 12 × 11 × 8 cm; invade y ulcera piel, invasión vascular, linfática y perineural presente, tres ganglios con metástasis supraclaviculares y 21 ganglios axilares con hiperplasia mixta. Conclusión: El carcinoma metaplásico de mama se asocia con indicadores de mal pronóstico, por lo que se requiere de una atención multidisciplinaria.
Revista Mexicana de Mastología, 2020
El tumor phyllodes maligno es uno de los tumores fibroepiteliales que representa el 1%, caracteri... more El tumor phyllodes maligno es uno de los tumores fibroepiteliales que representa el 1%, caracterizado por el crecimiento excesivo del estroma y aumento de mitosis, con recurrencias locales del 23 al 30% dentro de los dos a tres años, el tratamiento es la escisión quirúrgica con márgenes mayores a 1 cm para evitar las recurrencias, seguida de radioterapia, sin evidencia de quimioterapia. Se presenta el caso de una mujer de edad adulta, con tumor phyllodes maligno, con múltiples recurrencias, que tiene un comportamiento agresivo, con tratamiento multimodal, tratada con cirugía, radioterapia y quimioterapia.
Gaceta Mexicana de Oncolog�a, 2018
Introducción: El cáncer de mama es uno de los tumores malignos más frecuentes y una de las princi... more Introducción: El cáncer de mama es uno de los tumores malignos más frecuentes y una de las principales causas de mortalidad en nuestro país y alrededor del mundo. Implica alteraciones en la calidad de vida de las pacientes y un alto costo en el tratamiento tanto de las instituciones públicas como de las privadas. Es importante contar con recomendaciones basadas en evidencia que, al ser incorporadas en la toma de decisiones clínicas de forma rutinaria, ayuden a mejorar la calidad de la atención médica en estas pacientes. Objetivos: Esta guía de práctica clínica (GPC) contiene recomendaciones clínicas desarrolladas de forma sistematizada para asistir en la toma de decisiones de médicos especialistas, pacientes, cuidadores de pacientes y elaboradores de políticas públicas involucrados en el manejo de pacientes con cáncer de mama en estadios tempranos, localmente avanzados y metastásicos. Material y métodos: Este documento fue desarrollado por parte
To identify clinical, radiological, and histopathological characteristics that could be predictiv... more To identify clinical, radiological, and histopathological characteristics that could be predictive factors of microinvasive/invasive breast carcinoma in patients with diagnosis of ductal carcinoma in situ (DCIS) by core-needle biopsy. This is a retrospective study conducted from 2006-2017, which included women ≥18 years of age with initial DCIS, and who were treated with surgery. Final diagnosis was divided in DCIS and microinvasive/invasive carcinoma. 334 patients were included: 193 (57.8%) with DCIS and 141 (42.2%) with microinvasive/invasive carcinoma (microinvasive 5.1%, invasive 37.1%). Lymph node metastasis occurred in 16.3%. Differences between DCIS and microinvasive/invasive groups included the presence of palpable nodule (36.7% vs. 63.2%), radiological nodule (29% vs. 51%), bigger radiological-tumor size (1.2 cm vs. 1.7 cm), and larger microcalcification extension (2.5 cm vs. 3.1 cm), all of these variables p ≤0.05. Hormonal receptors and HER2 expression were similar. After logistic regression analysis, predictive factor of invasion was the presence of palpable nodule (OR = 4.072, 95%CI = 2.520-6.582, p <0.001) and radiological multicentric disease (OR = 1.677, 95%CI = 1.036-2.716, p = 0.035). In patients with DCIS, palpable nodule, and radiological multicentric disease, upgrade to microinvasive/invasive is high, and sentinel lymph node is recommended.
Molecular Oncology
Triple negative breast cancer (TNBC) represents an aggressive phenotype with poor prognosis compa... more Triple negative breast cancer (TNBC) represents an aggressive phenotype with poor prognosis compared with ER, PR, and HER2‐positive tumors. TNBC is a heterogeneous disease, and gene expression analysis has identified seven molecular subtypes. Accumulating evidence demonstrates that long non‐coding RNA (lncRNA) are involved in regulation of gene expression and cancer biology, contributing to essential cancer cell functions. In this study, we analyzed the expression profile of lncRNA in TNBC subtypes from 156 TNBC samples, and then characterized the functional role of LncKLHDC7B (ENSG00000226738). A total of 710 lncRNA were found to be differentially expressed between TNBC subtypes, and a subset of these altered lncRNA were independently validated. We discovered that LncKLHDC7B (ENSG00000226738) acts as a transcriptional modulator of its neighboring coding gene KLHDC7B in the immunomodulatory subtype. Furthermore, LncKLHDC7B knockdown enhanced migration and invasion, and promoted resistance to cellular death. Our findings confirmed the contribution of LncKLHDC7B to induction of apoptosis and inhibition of cell migration and invasion, suggesting that TNBC tumors with enrichment of LncKLHDC7B may exhibit distinct regulatory activity, or that this may be a generalized process in breast cancer. Additionally, in silico analysis confirmed for the first time that the low expression of KLHDC7B and LncKLHDC7B is associated with poor prognosis in patients with breast cancer.
Journal of Xiangya Medicine
Background: Asymptomatic cases of phyllodes tumor (PT) are extremely rare. The objective of the s... more Background: Asymptomatic cases of phyllodes tumor (PT) are extremely rare. The objective of the study was to describe the radiological features and to identify clinical differences between asymptomatic and symptomatic patients with PT in a Mexican population. Methods: A retrospective study was conducted including only surgically treated patients. Asymptomatic and symptomatic cases were compared. Descriptive statistical techniques were used. Radiological features were reported in asymptomatic cases. Results: Over 10 years, 305 women with PT were included (307 tumors). The 25 (8.1%) asymptomatic patients were 6 years older than symptomatic patients (47.6 vs. 41.2 years; P=0.005), with more pregnancies (3 vs. 2; P=0.013), more breastfeeding (80% vs. 61%; P=0.042), with smaller tumor size in radiological, and pathology studies (P<0.001), with more conservative surgeries (91.7% vs. 68%; P=0.005), and more benign PT (88%). Mammographic images in asymptomatic cases showed a nodule, mostly isodense, and with wellcircumscribed margins. Ultrasound (US) demonstrated macrolobular nodules, with hypoechoic pattern and well-circumscribed margins. Percutaneous core-needle biopsies reported 45.5% as PT in asymptomatic cases. Conclusions: As we expected, asymptomatic PTs were smaller than symptomatic cases. Even asymptomatic PT was not to high suspicious nodules in older patients, we recommend excisional biopsy because radiological features are indistinguishable from those of fibroadenomas, and the only <50% were reported as PT with percutaneous needle biopsy.
Molecular Oncology, Feb 9, 2019
Triple negative breast cancer (TNBC) represents an aggressive phenotype with poor prognosis compa... more Triple negative breast cancer (TNBC) represents an aggressive phenotype with poor prognosis compared with ER, PR, and HER2-positive tumors. TNBC is a heterogeneous disease, and gene expression analysis has identified seven molecular subtypes. Accumulating evidence demonstrates that long non-coding RNA (lncRNA) are involved in regulation of gene expression and cancer biology, contributing to essential cancer cell functions. In this study, we analyzed the expression profile of lncRNA in TNBC subtypes from 156 TNBC samples, and then characterized the functional role of LncKLHDC7B (ENSG00000226738). A total of 710 lncRNA were found to be differentially expressed between TNBC subtypes, and a subset of these altered lncRNA were independently validated. We discovered that LncKLHDC7B (ENSG00000226738) acts as a transcriptional modulator of its neighboring coding gene KLHDC7B in the immunomodulatory subtype. Furthermore, LncKLHDC7B knockdown enhanced migration and invasion, and promoted resistance to cellular death. Our findings confirmed the contribution of LncKLHDC7B to induction of apoptosis and inhibition of cell Abbreviations ADAM9, ADAM metallopeptidase domain 9; AMOT, angiomotin; APP, amyloid beta precursor protein;
Cirugía y cirujanos, May 1, 2015
Background: Breast cancer is the leading oncological cause of death in Mexican women over 25 year... more Background: Breast cancer is the leading oncological cause of death in Mexican women over 25 years old. Given the need to improve postoperative cosmetic results in patients with breast cancer, oncoplastic surgery has been developed, which allows larger tumour resections and minor cosmetic alterations. Objective: To determine the oncological feasibility and cosmetic outcome of oncoplastic surgery at the Instituto de Enfermedades de la Mama, FUCAM, AC. Material and methods: A review was conducted from January 2010 to July 2013, which included patients with breast cancer diagnosis treated with conventional breast-conserving surgery or with oncoplastic surgery in the Instituto de Enfermedades de la Mama, FUCAM AC. Clinical and histopathological parameters were compared between the two groups, and a questionnaire of cosmetic satisfaction and quality of life was applied. Results: Of the 171 patients included, 95 of them were treated with conventional breastconserving surgery and 76 with oncoplastic surgery. Pathological tumour size was significantly larger in patients treated with oncoplastic surgery (p = 0.002). There were no differences found between the groups as regards the number of patients with positive surgical margin, the rate of complications, and cosmetic satisfaction. Conclusion: This study demonstrates the oncological feasibility and high cosmetic satisfaction of oncoplastic surgery with minimal psycho-social impact on patients.
Scientific Reports, 2020
Breast cancer (BRCA) is a serious public health problem, as it is the most frequent malignant tum... more Breast cancer (BRCA) is a serious public health problem, as it is the most frequent malignant tumor in women worldwide. BRCA is a molecularly heterogenic disease, particularly at gene expression (mRNAs) level. Recent evidence shows that coding RNAs represent only 34% of the total transcriptome in a human cell. The rest of the 66% of RNAs are non-coding, so we might be missing relevant biological, clinical or regulatory information. In this report, we identified nine novel tumor types from TCGA with FAM83H-AS1 deregulation. We used survival analysis to demonstrate that FAM83H-AS1 expression is a marker for poor survival in IHC-detected ER and PR positive BRCA patients and found a significant correlation between FAM83H-AS1 overexpression and tamoxifen resistance. Estrogen and Progesterone receptor expression levels interact with FAM83H-AS1 to potentiate its effect in OS prediction. FAM83H-AS1 silencing impairs two important breast cancer related pathways: cell migration and cell death...
Cancer Epidemiology, Biomarkers & Prevention, 2020
Breast cancer is a relevant public health problem that affects millions of women worldwide. Breas... more Breast cancer is a relevant public health problem that affects millions of women worldwide. Breast tumors are recognized as a clinically and molecular heterogeneous pathology, but the genomic basis of its variability remains poorly understood, mainly regarding the comprehensive of ethnicity/racial disparities and their consequences in genomics studies. Moreover, most of the comprehensive molecular characterizations are predominantly centered on Caucasian population. Thus, we deeply characterized the molecular architecture of breast cancer in a set of Mexican patients through genomic and transcriptomic portraits. We explored the molecular features of breast cancers in Mexican-Hispanic (HM) women and compared them with public multi-ethnic datasets. HM patients presented an earlier onset of the disease, in particular in the aggressive Basal-like/triple negative and Luminal B subtypes. The significant E17K hotspot mutation in AKT1 gene occurred in 8% of the HM tumors, an enriched preval...
Nature Communications, 2021
Breast cancer is a heterogeneous pathology, but the genomic basis of its variability remains poor... more Breast cancer is a heterogeneous pathology, but the genomic basis of its variability remains poorly understood in populations other than Caucasians. Here, through DNA and RNA portraits we explored the molecular features of breast cancers in a set of Hispanic-Mexican (HM) women and compared them to public multi-ancestry datasets. HM patients present an earlier onset of the disease, particularly in aggressive clinical subtypes, compared to non-Hispanic women. The age-related COSMIC signature 1 was more frequent in HM women than in those from other ancestries. We found the AKT1E17K hotspot mutation in 8% of the HM women and identify the AKT1/PIK3CA axis as a potentially druggable target. Also, HM luminal breast tumors present an enhanced immunogenic phenotype compared to Asiatic and Caucasian tumors. This study is an initial effort to include patients from Hispanic populations in the research of breast cancer etiology and biology to further understand breast cancer disparities.
Frontiers in Oncology, 2021
Breast cancer (BRCA) is a serious public health problem, as it is the most frequent malignant tum... more Breast cancer (BRCA) is a serious public health problem, as it is the most frequent malignant tumor in women worldwide. BRCA is a molecularly heterogeneous disease, particularly at gene expression (mRNAs) level. Recent evidence shows that coding RNAs represent only 34% of the total transcriptome in a human cell. The rest of the 66% of RNAs are non−coding, so we might be missing relevant biological, clinical or regulatory information. In this report, we identified two novel tumor types from TCGA with LINC00460 deregulation. We used survival analysis to demonstrate that LINC00460 expression is a marker for poor overall (OS), relapse-free (RFS) and distant metastasis-free survival (DMFS) in basal-like BRCA patients. LINC00460 expression is a potential marker for aggressive phenotypes in distinct tumors, including HPV-negative HNSC, stage IV KIRC, locally advanced lung cancer and basal-like BRCA. We show that the LINC00460 prognostic expression effect is tissue-specific, since its upreg...
Scientific Reports, 2020
Breast cancer is the most commonly diagnosed neoplasm in women worldwide with a well-recognized h... more Breast cancer is the most commonly diagnosed neoplasm in women worldwide with a well-recognized heterogeneous pathology, classified into four molecular subtypes: Luminal A, Luminal B, HER2-enriched and Basal-like, each one with different biological and clinical characteristics. Long non-coding RNAs (lncRNAs) represent 33% of the human transcriptome and play critical roles in breast carcinogenesis, but most of their functions are still unknown. Therefore, cancer research could benefit from continued exploration into the biology of lncRNAs in this neoplasm. We characterized lncRNA expression portraits in 74 breast tumors belonging to the four molecular subtypes using transcriptome microarrays. To infer the biological role of the deregulated lncRNAs in the molecular subtypes, we performed co-expression analysis of lncRNA–mRNA and gene ontology analysis. We identified 307 deregulated lncRNAs in tumor compared to normal tissue and 354 deregulated lncRNAs among the different molecular sub...
Frontiers in Oncology, 2020
Studies have suggested a potential role of somatic mitochondrial mutations in cancer development.... more Studies have suggested a potential role of somatic mitochondrial mutations in cancer development. To analyze the landscape of somatic mitochondrial mutation in breast cancer and to determine whether mitochondrial DNA (mtDNA) mutational burden is correlated with overall survival (OS), we sequenced whole mtDNA from 92 matchedpaired primary breast tumors and peripheral blood. A total of 324 germline variants and 173 somatic mutations were found in the tumors. The most common germline allele was 663G (12S), showing lower heteroplasmy levels in peripheral blood lymphocytes than in their matched tumors, even reaching homoplasmic status in several cases. The heteroplasmy load was higher in tumors than in their paired normal tissues. Somatic mtDNA mutations were found in 73.9% of breast tumors; 59% of these mutations were located in the coding region (66.7% non-synonymous and 33.3% synonymous). Although the CO1 gene presented the highest number of mutations, tRNA genes (T, C, and W), rRNA 12S, and CO1 and ATP6 exhibited the highest mutation rates. No specific mtDNA mutational profile was associated with molecular subtypes of breast cancer, and we found no correlation between mtDNA mutational burden and OS. Future investigations will provide insight into the molecular mechanisms through which mtDNA mutations and heteroplasmy shifting contribute to breast cancer development.
Human Genomics, 2019
Interpretation of variants of unknown significance (VUS) in genetic tests is complicated in ethni... more Interpretation of variants of unknown significance (VUS) in genetic tests is complicated in ethnically diverse populations, given the lack of information regarding the common spectrum of genetic variation in clinically relevant genes. Public availability of data obtained from high-throughput genotyping and/or exome massive parallel sequencing (MPS)-based projects from several thousands of outbred samples might become useful tools to evaluate the pathogenicity of a VUS, based on its frequency in different populations. In the case of the Mexican and other Latino populations, several thousands of samples have been genotyped or sequenced during the last few years as part of different efforts to identify common variants associated to common diseases. In this report, we analyzed Mexican population data from a sample of 3985 outbred individuals, and additional 66 hereditary breast cancer patients were analyzed in order to better define the spectrum of common genomic variation of the BRCA1 and BRCA2 genes. Our analyses identified the most common genetic variants in these clinically relevant genes as well as the presence and frequency of specific pathogenic mutations present in the Mexican population. Analysis of the 3985 population samples by MPS identified three pathogenic mutations in BRCA1, only one population sample showed a BRCA1 exon 16-17 deletion by MLPA. This resulted in a basal prevalence of deleterious mutations of 0.10% (1:996) for BRCA1 and 11 pathogenic mutations in BRCA2, resulting in a basal prevalence of deleterious mutations of 0.276% (1:362) for BRCA2, combined of 0.376% (1:265). Separate analysis of the breast cancer patients identified the presence of pathogenic mutations in 18% (12 pathogenic mutations in 66 patients) of the samples by MPS and 13 additional alterations by MLPA. These results will support a better interpretation of clinical studies focused on the detection of BRCA mutations in Mexican and Latino populations and will help to define the general prevalence of deleterious mutations within these populations.
Cancer Research, 2019
BACKGROUND: Advances in chemotherapy and target therapy have made treatment of breast cancer (BC)... more BACKGROUND: Advances in chemotherapy and target therapy have made treatment of breast cancer (BC) more effective; however, survivors of BC suffer an increased burden of cardiotoxicity. The aim of this study is to determine the risk factors in a Mexican patients (pt) METHODS:Observational study of a cohort of pt with locally BC and Her2 (+++) treated with trastuzumab (TZ). According to clinical stage, they underwent to surgery or neoadjuvant chemotherapy, scheme was at the decision of the physician. The main schemes: AC-T, EC-T, FAC-T, FEC-T, Paclitaxel, intravenous (IV) or subcutaneous TZ. The doses were according to NCCN guidelines and the route of administration of TZ was decision of the oncologist. Ventriculography was performed basally, at 4,8,12 cycles and at the end of treatment. If the pt presented a decrease in the ejection fraction>10% with/without symptoms, they received cardioprotection (metoprolol+atorvastatin). It was the oncologist decision to suspend chemotherapy a...
Cirugía y cirujanos
Thoracic trauma accounts for 25% of deaths due to trauma. Chest trauma patients generally present... more Thoracic trauma accounts for 25% of deaths due to trauma. Chest trauma patients generally present to the emergency room with pneumo- or hemothorax. According to the majority of the studies, management of closed thoracostomy for trauma includes the use of antimicrobial drugs to prevent infectious complications, but this has not been proven to be beneficial. We undertook this study to evaluate antimicrobial use in thoracic trauma patients with closed thoracostomy and its impact on the development of infectious complications. We carried out a prospective, randomized, double blind, comparative study. Patients with isolated chest trauma requiring closed thoracostomy were divided into two groups. Group A received cefalotin, and group B received placebo. Ages ranged from 15-65 years. Results were analyzed with chi(2) and Fisher exact test. One hundred twenty six patients were included in this study. There were 63 patients in each group with similar demographic characteristics. The mean len...
Revista Mexicana de Mastología, 2019
Revista Mexicana de Mastología, 2020
El carcinoma metaplásico de células escamosas de mama representa menos del 1% de todos los carcin... more El carcinoma metaplásico de células escamosas de mama representa menos del 1% de todos los carcinomas de mama invasores. Reporte de caso: Mujer de 47 años con carcinoma metaplásico con diferenciación epidermoide. Inmunohistoquímica con receptores de estrógeno 30%, receptores de progesterona 5%, Her2 negativo, Ki 67 80%. Se realiza mastectomía de limpieza con resección amplia de piel y cobertura cutánea con colgajo dorsal. Estudio histopatológico definitivo: carcinoma metaplásico con diferenciación epidermoide de 12 × 11 × 8 cm; invade y ulcera piel, invasión vascular, linfática y perineural presente, tres ganglios con metástasis supraclaviculares y 21 ganglios axilares con hiperplasia mixta. Conclusión: El carcinoma metaplásico de mama se asocia con indicadores de mal pronóstico, por lo que se requiere de una atención multidisciplinaria.
Revista Mexicana de Mastología, 2020
El tumor phyllodes maligno es uno de los tumores fibroepiteliales que representa el 1%, caracteri... more El tumor phyllodes maligno es uno de los tumores fibroepiteliales que representa el 1%, caracterizado por el crecimiento excesivo del estroma y aumento de mitosis, con recurrencias locales del 23 al 30% dentro de los dos a tres años, el tratamiento es la escisión quirúrgica con márgenes mayores a 1 cm para evitar las recurrencias, seguida de radioterapia, sin evidencia de quimioterapia. Se presenta el caso de una mujer de edad adulta, con tumor phyllodes maligno, con múltiples recurrencias, que tiene un comportamiento agresivo, con tratamiento multimodal, tratada con cirugía, radioterapia y quimioterapia.
Gaceta Mexicana de Oncolog�a, 2018
Introducción: El cáncer de mama es uno de los tumores malignos más frecuentes y una de las princi... more Introducción: El cáncer de mama es uno de los tumores malignos más frecuentes y una de las principales causas de mortalidad en nuestro país y alrededor del mundo. Implica alteraciones en la calidad de vida de las pacientes y un alto costo en el tratamiento tanto de las instituciones públicas como de las privadas. Es importante contar con recomendaciones basadas en evidencia que, al ser incorporadas en la toma de decisiones clínicas de forma rutinaria, ayuden a mejorar la calidad de la atención médica en estas pacientes. Objetivos: Esta guía de práctica clínica (GPC) contiene recomendaciones clínicas desarrolladas de forma sistematizada para asistir en la toma de decisiones de médicos especialistas, pacientes, cuidadores de pacientes y elaboradores de políticas públicas involucrados en el manejo de pacientes con cáncer de mama en estadios tempranos, localmente avanzados y metastásicos. Material y métodos: Este documento fue desarrollado por parte
To identify clinical, radiological, and histopathological characteristics that could be predictiv... more To identify clinical, radiological, and histopathological characteristics that could be predictive factors of microinvasive/invasive breast carcinoma in patients with diagnosis of ductal carcinoma in situ (DCIS) by core-needle biopsy. This is a retrospective study conducted from 2006-2017, which included women ≥18 years of age with initial DCIS, and who were treated with surgery. Final diagnosis was divided in DCIS and microinvasive/invasive carcinoma. 334 patients were included: 193 (57.8%) with DCIS and 141 (42.2%) with microinvasive/invasive carcinoma (microinvasive 5.1%, invasive 37.1%). Lymph node metastasis occurred in 16.3%. Differences between DCIS and microinvasive/invasive groups included the presence of palpable nodule (36.7% vs. 63.2%), radiological nodule (29% vs. 51%), bigger radiological-tumor size (1.2 cm vs. 1.7 cm), and larger microcalcification extension (2.5 cm vs. 3.1 cm), all of these variables p ≤0.05. Hormonal receptors and HER2 expression were similar. After logistic regression analysis, predictive factor of invasion was the presence of palpable nodule (OR = 4.072, 95%CI = 2.520-6.582, p <0.001) and radiological multicentric disease (OR = 1.677, 95%CI = 1.036-2.716, p = 0.035). In patients with DCIS, palpable nodule, and radiological multicentric disease, upgrade to microinvasive/invasive is high, and sentinel lymph node is recommended.
Molecular Oncology
Triple negative breast cancer (TNBC) represents an aggressive phenotype with poor prognosis compa... more Triple negative breast cancer (TNBC) represents an aggressive phenotype with poor prognosis compared with ER, PR, and HER2‐positive tumors. TNBC is a heterogeneous disease, and gene expression analysis has identified seven molecular subtypes. Accumulating evidence demonstrates that long non‐coding RNA (lncRNA) are involved in regulation of gene expression and cancer biology, contributing to essential cancer cell functions. In this study, we analyzed the expression profile of lncRNA in TNBC subtypes from 156 TNBC samples, and then characterized the functional role of LncKLHDC7B (ENSG00000226738). A total of 710 lncRNA were found to be differentially expressed between TNBC subtypes, and a subset of these altered lncRNA were independently validated. We discovered that LncKLHDC7B (ENSG00000226738) acts as a transcriptional modulator of its neighboring coding gene KLHDC7B in the immunomodulatory subtype. Furthermore, LncKLHDC7B knockdown enhanced migration and invasion, and promoted resistance to cellular death. Our findings confirmed the contribution of LncKLHDC7B to induction of apoptosis and inhibition of cell migration and invasion, suggesting that TNBC tumors with enrichment of LncKLHDC7B may exhibit distinct regulatory activity, or that this may be a generalized process in breast cancer. Additionally, in silico analysis confirmed for the first time that the low expression of KLHDC7B and LncKLHDC7B is associated with poor prognosis in patients with breast cancer.
Journal of Xiangya Medicine
Background: Asymptomatic cases of phyllodes tumor (PT) are extremely rare. The objective of the s... more Background: Asymptomatic cases of phyllodes tumor (PT) are extremely rare. The objective of the study was to describe the radiological features and to identify clinical differences between asymptomatic and symptomatic patients with PT in a Mexican population. Methods: A retrospective study was conducted including only surgically treated patients. Asymptomatic and symptomatic cases were compared. Descriptive statistical techniques were used. Radiological features were reported in asymptomatic cases. Results: Over 10 years, 305 women with PT were included (307 tumors). The 25 (8.1%) asymptomatic patients were 6 years older than symptomatic patients (47.6 vs. 41.2 years; P=0.005), with more pregnancies (3 vs. 2; P=0.013), more breastfeeding (80% vs. 61%; P=0.042), with smaller tumor size in radiological, and pathology studies (P<0.001), with more conservative surgeries (91.7% vs. 68%; P=0.005), and more benign PT (88%). Mammographic images in asymptomatic cases showed a nodule, mostly isodense, and with wellcircumscribed margins. Ultrasound (US) demonstrated macrolobular nodules, with hypoechoic pattern and well-circumscribed margins. Percutaneous core-needle biopsies reported 45.5% as PT in asymptomatic cases. Conclusions: As we expected, asymptomatic PTs were smaller than symptomatic cases. Even asymptomatic PT was not to high suspicious nodules in older patients, we recommend excisional biopsy because radiological features are indistinguishable from those of fibroadenomas, and the only <50% were reported as PT with percutaneous needle biopsy.