Association study of miR-22 and miR-335 expression levels and G2 assay related inherent radiosensitivity in peripheral blood of ductal carcinoma breast cancer patients (original) (raw)
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Journal of Radiation Research and Applied Sciences, 2022
Background: MiRNA-21 (miR-21) promotes the initiation and progression of tumor by initiating cell cycle differentiation, while miR-34a induces apoptosis through activating the tumor-suppressor gene p53, and by repressing the anti-apoptotic protein, B-cell lymphoma 2 (Bcl2). Aim: To investigate if the expression folds change of circulating miR-21 and miR-34a could be a potential marker to evaluate the response of female breast cancer (BC) patients to the chemo-radiotherapy treatment. Subjects: and Methods: The study included 159 BC patients and 58 healthy females. Among patients' 56 were Luminal A, 41 Luminal B, 15 Her-2/neu and 47 Basal like. Regarding stages, 118 BC patient were stage II, 12 stage I, and 29 stage III. Data of miR-21 and miR-34a were correlated with Bcl2, the breast cancer susceptibility genes BRCA1, and BRCA2, and p53. Results: The expression of miR-21 is upregulated (p < 0.001) in BC patients while miR-34a, is downregulated (p < 0.001), compared to control. The application of chemo-radiotherapy treatment decreased (p < 0.001) miR-21 and increased (p < 0.001) miR-34a. MiR-21 directly correlates with Bcl2 (p < 0.001) while miR-34a directly correlates with BRAC1, BRAC2 and p53 (p < 0.001). Conclusion: miR-34a and miR-21 may be considered as promising non-invasive biomarkers in evaluating the response of BC female patients to chemo-radiotherapy. Peer review under responsibility of The Egyptian Society of Radiation Sciences and Applications.
Plasma Level Of miR-21 And miR-451 In Primary And Recurrent Breast Cancer Patients
Breast Cancer: Targets and Therapy
Purpose: MiR-21 and miR-451 are closely associated with tumor initiation, drug resistance, and recurrence of breast cancer (BC). This study was conducted to evaluate the possible value of the plasma level of miR-21 and miR-451 as potential biomarkers for the detection of primary and recurrent BC. Patients and methods: In this descriptive-analytical study, the plasma level of miR-21 and miR-451 was measured in 23 primary BC patients, 24 recurrent (local/distant metastasis) BC patients, and 24 aged-match women as healthy controls using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Finally, data were analyzed using SPSS software, and the area under the receiver operating characteristic (ROC) curve of miRNAs was measured. Results: The plasma level of miR-21 was significantly increased in both groups of primary (P<0.001) and recurrent (P<0.001) BC patients in comparison with healthy women. However, the plasma level of miR-451 was not significantly changed in primary (P=0.065) and recurrent (P=0.06) BC patients than healthy controls. The elevation of both miR-21 and miR-451 plasma level was not significantly changed in recurrent patients compared with non-recurrent (primary) patients (P=0.481, and P=1, respectively). Based on the ROC analyses, the areas under the curves (AUC) for miR-21 in discriminating primary BC and recurrent BC patients from healthy controls were 0.828 (95% CI: 0.712 to 0.944) and 0.865 (95% CI: 0.756 to 0.974), respectively. Conclusion: These data indicating that plasma miR-21 may be useful as a biomarker for the detection of both primary and recurrent BC. However, plasma miR-451 lacks enough sensitivity in the detection of primary and recurrent BC, and more studies are needed in this area.
MiR-328 May be Considered as an Oncogene in Human Invasive Breast Carcinoma
Background: The recent investigations have rendered microRNAs (miRs) as a novel biomarker in cancer research. In fact, alteration in miR expression may be associated with tumor suppression, tumorigenesis, metastasis, and poor prognosis in human breast cancer (BC). Objectives: The aim of this clinical experimental study was to measure the miR-328 expression level in breast cancer tissues, at first. Then, we tried to find out any possible correlation between miR-328 and prognostic and predictive biomarkers in BC. Both of these two objectives were investigated for the first time; and we did not find any similar survey measuring the expression level of miR-328 in both tumor and non-tumor breast tissues. This research was conducted in Iran (Ahvaz, Khuzestan), between December 2013 and April 2014. Furthermore, we did not find any previous document investigating the correlation between miR-328 expression level and prognostic factors in BC. Due to the lack of similar studies intending to measure the expression level of miR-328 in tumor and adjacent non-tumor tissues, we decided to carry out a pilot study. Methods: We measured the expression level of miR-328 by Poly (A) real-time PCR based on SYBR Green-I in 28 fresh samples of BC tissues and 28 samples of normal adjacent tissues, including invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and ductal carcinoma in situ (DCIS). We tried to attribute the results to clinicopathologic features such as status of estrogen and progesterone receptors (ER/PR), HER2/neu (HER2), P53 and also Ki67 labeling (Ki67-LI). Results: The results showed that the miR-328 median level of expression was 0.88 (2-∆∆Ct) (25 th-75 th percentile, 0.07-2.34). It means that the expression level increased in tumor tissues compared to normal adjacent tissues (NATs). However, a statistically significant correlation between the miR-328 median expression level and prognostic factors, including pathologic diagnosis, age, and also the status of ER, PR, HER2, and Ki67-LI was not observed (P > 0.05). Conclusions: Therefore, it might be possible to consider miR-328 as an oncogene; but not necessarily an oncomiR, in human BC.
International Journal of General Medicine, 2022
Background: miRNA-21, one of breast cancer (BC) predictive markers, is now gaining cardinal attention from researchers worldwide to evaluate BC patients' survival rate. However, cancer staging, hormonal status, and other BC markers still have to be discussed. We aim to determine the relationship between miRNA-21 and associating factors such as BC staging, other tumor markers, and hormonal status to predict the 2-year survival rate of BC patients. Methods: We conducted a prospective cohort study on 49 BC patients (26 early stage, 23 advanced stage). Apart from cancer staging, we also examined CEA, Ca15-3, and hormonal status (ER, PR, Her2) and correlated them with miRNA-21 to predict 2-year survival rate. We did bivariate, multivariate, and survival analyses to determine the link between miRNA-21 and those factors to prognosticate on 2-year survival rate. Results: There are significances between advanced and loco-regional stage (p < 0.001); high and low miRNA-21 (p = 0.002) and CA 15-3 (p = 0.001), and low survival rate in patients with ER/PR-Her2-status (p=0.0015). Cox proportional hazard showed miRNA-21 (Adjusted HR 1.41; 95% CI = 1.205-1.632), cancer stage (Adjusted HR 9.5; 95% CI = 1.378-20.683), and CA15-3 (Adjusted HR 4.64; 95% CI = 1.548-13.931) affected patients' mortality within 2 years. Conclusion: Low two-year survival rate depends on miRNA-21, cancer stage, CA15-3, and ER/PR-Her2-. Cancer stage is robustly associated with miRNA-21 in predicting 2-year survival rate.
Circulating miR-200c and miR-141 and outcomes in patients with breast cancer
BMC Cancer, 2015
Background: The deregulation of microRNAs in both tumours and blood has led to the search for microRNAs to indicate the presence of cancer and predict prognosis. We hypothesize the deregulation of miR-200c/miR-141 in the whole blood can identify breast cancer (BC), and could be developed into a prognostic signature. Methods: The expression of miR-200c and miR-141 were examined in bloods (57 stage I-IV BC patients and 20 age-matched controls) by quantitative reverse-transcription PCR. The associations of circulating microRNAs with clinic and pathological characteristics were analysed. Their effects on survival were analysed by the Kaplan-Meier method and Cox regressions. Results: MiR-200c was down regulated (P < 0.0001) in the blood of BC patients, yielded an area under the ROC curve of 0.79 (90% sensitivity, 70.2% specificity) in discriminating BC from controls. Circulating miR-141 was not discriminating. MiR-200c and miR-141 in the blood of BC patients were inversely correlated (P = 0.019). The miR-200c levels were numerically higher in stage IV and tumours with lower MIB-1. MiR-141 was significantly higher in the blood of patients with stage I-III, lymph node metastasis, and HER2 negative tumours. High blood expression of miR-200c and/or low expression of miR-141 was associated with unfavourable overall survival (hazard ratio, 3.89; [95% CI: 1.28-11.85]) and progression-free survival (3.79 [1.41-10.16]) independent of age, stage and hormonal receptors. Conclusions: Circulating miR-200c and miR-141 were deregulated in BC comparing with controls. Furthermore, miR-200c and miR-141 were independent prognostic factors and associated with distinct outcomes of BC patients.
Journal of advanced biomedical sciences, 2022
Background & Objective: Breast cancer (BC) is a complex genetic disease that has an average annual incidence of one million people and is the second leading cause of death among women in the world. Therefore, a better understanding of tumor biology and the determination of biomarkers for early diagnosis of disease is essential. MicroRNAs and long non-coding RNAs are novel gene regulators that play key roles in tumor initiation and progression. The current study was performed to assess the biomarker potential. This study performed a combination of in-silico and experimental investigations of altered miRNAs in BC to assess the use of miRNAs as novel biomarkers for early detection and prognosis prediction of patients with BC. Materials & Methods: We searched the miRNA expression patterns of BC from three expression arrays (GSE58606, GSE38867, and GSE40525) from the Gene Expression Omnibus (GEO) database to recognize differentially expressed miRNAs (DEMs) between BC tissues and normal adjacent samples. Using "Limma" package's Quantile Normalization function and INMEX bioinformatic tool, hub DEMs were identified. MiRNAs targeted genes were found and visualized via the miRWalk and miRTargetLink databases and their Enrichment analysis was performed for identified genes. Due to more validation of DEGs, GSE70951, an independent expression array dataset, was analyzed. By merging DEMs and DEGs, miRNA-mRNA network was constructed. After elucidation of hub miRNAs, the capacity of detected miRNAs to differentiate BC from adjacent controls was estimated by Kaplan-Meier analysis. Furthermore, RT-qPCR on 100 BC samples and 100 adjacent non-tumor tissues was performed to validate the in-silico results. Results: According to our study, in BC samples, miR-662 was differentially downregulated in comparison with normal adjacent tissues. Conclusion: Altogether, miR-662 can be considered as a viable target for BC diagnostics and treatment.
Asian Pacific Journal of Cancer Prevention
Background: Breast cancer (BC) is the second most common cancer worldwide. MicroRNAs are a group of non-coding, single stranded RNAs of ~ 22 nucleotides, which regulate gene expression at the post-transcriptional level. Circulating miRNAs have been found as potential blood based predictive biomarkers. Purpose: we aim to evaluate miR-34a and miR-125b to predict outcome from neoadjuvant chemotherapy in Egyptian BC patients. Methodology: Quantitative assessment of plasma miR-34a and miR-125b expression was performed by qRT-PCR. Thirty nine newly diagnosed locally advanced BC female patients with 10 age and sex matched healthy volunteers were included in the study. Results: We performed ROC curve analysis to evaluate the diagnostic value for the miR-34a with AUCs = 0.995, cutoff point of 2.57 sensitivity 97.4%, specificity 100%, PPV 100%, NPV 83.3% and accuracy 97.7%. miR-125b had AUC = 0.68 and a cutoff point of 8.69 with sensitivity 66.7%, specificity 70.0%, PPV 90.6%, NPV 41.2% and accuracy 73.5%. miR-34a expression were significantly higher in BC patients compared to controls with p value <0.001*. Also, miR-34a expression level was significantly higher in patients with progressive disease with P value =0.03*. However, miR-125b expression levels were insignificantly higher in responsive patients with p value = 0.2. Conclusion: miRNAs are crucial candidates for novel molecular targeted therapies due to their capability to regulate numerous genes in molecular pathways. Our data suggest that circulating miR-34a and miR-125b expression levels could be promising highly accurate non-invasive biomarkers in diagnosing BCs. miR-34a can predict chemotherapeutic resistance associated with higher expression levels in non-responsive patients.
The Association of miR-451 and miR-21 in Plasma with Lymph Node Metastases in Breast Cancer
Journal of Babol University of Medical Sciences, 2018
BACKGROUND AND OBJECTIVE: The expression of some circulating microRNAs (miRNAs) in biological fluids of healthy individuals is different from cancerous patients. circulating miRNAs are a new class of cancer biomarkers because of their high stability and sensitivity, ease of measurement and specificity due to their correlation with various cancer states. According to the miR-451 and miR-21 functions in the metastasis of some cancers, the aim of this study was to investigate the differences of expression levels of miR-451 and miR-21 in the plasma of breast cancer (BC) patients with and without lymph nodes metastasis (LNM). METHODS: In this descriptive-analytical study, blood samples were collected from 47 women with BC and 24 healthy women with mammography confirmation. The presence/or absence of LNM was recognized from patients' medical records. The expression levels of miR-451 and miR-21 in the plasma, were investigated using Real-Time PCR. FINDINGS: The median of expression of miR-451 in BC patients with LNM and without LNM was 1.739 and 3.187, respectively, and its expression in lymph node metastatic patients decreased 0.444 folds in comparison with nonmetastatic patients (p=0.031). The median of expression of miR-21 in patients with LNM and in non-metastatic lymph nodes patients was 5.922 and 2.157, respectively, and its expression in metastatic status was 2 folds higher than nonmetastatic (p=0.029). CONCLUSION: The results of this study indicated that decreased miR-451 and increased miR-21 expression in plasma of BC patients was associated with LNM status.
The Indonesian Biomedical Journal
BACKGROUND: Carbohydrate antigens 15-3 (CA 15-3) is a conventional tumor marker in breast cancer, with low sensitivity and specificity. MicroRNA (miRNA)-21 showed its stability in circulation and could serve as powerful biomarker. The aim of this study was to evaluate miRNA-21 as breast cancer biomarker compared to CA 15-3 in Indonesian population.METHODS: Circulating plasma miRNA-21 expression was measured using qRT-PCR in 49 patients at various stages of breast cancer and 16 healthy controls. The relative expression value of miRNA-21 was calculated using 2-ΔΔCt. Meanwhile, CA 15-3 was quantified using electrochemiluminescence immunoassay (ECLIA) methods. The results of miRNA-21 and CA 15-3 plasma circulating expression were compared with controls at each stage and between stages of breast cancer.RESULTS: CA 15-3 median level in breast cancer group was 1.60 times higher compared to control group (p=0.019), 21.00 m/mL and 13.05 m/mL, respectively. Median miRNA-21 expression in breas...