Allele frequency deviation (AFD) as a new prognostic model to predict overall survival in lung adenocarcinoma (LUAD) (original) (raw)
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2020
Background Due to the late and poor prognosis of non-small lung cancer(NSCLC), the mortality of patients is high, underlines the need to identify a credible prognostic marker for NSCLC patients. The aim of our study is to examine the association of allele frequency deviation (AFD) with the patient's survival, as well as identification and validation of a new prognostic signature to predict NSCLC overall survival(OS).Methods First, we developed a new algorithm to calculate AFD from whole-exome sequencing(WES) data, then we compared the predictability of the patient's survival between AFD, tumor mutation burden (TMB) and change of variants allele frequency (dVAF). Second, we overlapped the differentially expressed genes (DEGs) from our data with the genes associated with the survival of The Cancer Genome Atlas (TCGA) database to confirm all genes significantly related to the survival of lung cancer. We identified 149 genes, 31 of which are new genes and have not been reported ...
Analysis of genomic and transcriptomic variations as prognostic signature for lung adenocarcinoma
BMC Bioinformatics, 2020
Background Lung cancer is the leading cause of the largest number of deaths worldwide and lung adenocarcinoma is the most common form of lung cancer. In order to understand the molecular basis of lung adenocarcinoma, integrative analysis have been performed by using genomics, transcriptomics, epigenomics, proteomics and clinical data. Besides, molecular prognostic signatures have been generated for lung adenocarcinoma by using gene expression levels in tumor samples. However, we need signatures including different types of molecular data, even cohort or patient-based biomarkers which are the candidates of molecular targeting. Results We built an R pipeline to carry out an integrated meta-analysis of the genomic alterations including single-nucleotide variations and the copy number variations, transcriptomics variations through RNA-seq and clinical data of patients with lung adenocarcinoma in The Cancer Genome Atlas project. We integrated significant genes including single-nucleotide...
2021
Significant advancement has been made in the treatment of patients with on the basis of the molecular profile. However, no such molecular target exists for squamous cell carcinoma (SQCC). Whole-exome sequencing (WES) has been in wide use for the discovery of new genetic pulmonary adenocarcinoma (ADCA) markers, which may offer more information for the development of personalized medicine for all subtypes of lung cancer. The aim of the current study is to find out novel genetic markers for non-small-cell lung carcinoma (NSCLC). WES of 19 advanced NSCLC patients (10 ADCA and 9 SQCC) was done on the Illumina HiSeq 2000 (Illumina Inc., USA). Variant calling was performed using GATK HaplotypeCaller and subsequent the impacts of variants on protein structure or function were predicted using SnpEff and ANNOVAR. Clinical impact of variants was evaluated using cancer-related archives. Somatic variants were further prioritized using knowledge-driven variant interpretation approach. Functionall...
JCO Precision Oncology, 2019
PURPOSE Broad-panel sequencing of tumors facilitates routine care of people with cancer as well as clinical trial matching for novel genome-directed therapies. We sought to extend the use of broad-panel sequencing results to survival stratification and clinical outcome prediction. METHODS By using sequencing results from a cohort of 1,054 patients with advanced lung adenocarcinomas, we developed OncoCast, a machine learning tool for survival risk stratification and biomarker identification. RESULTS With OncoCast, we stratified this patient cohort into four risk groups on the basis of tumor genomic profile. Patients whose tumors harbored a high-risk profile had a median survival of 7.3 months (95% CI, 5.5 to 10.9 months) compared with a low-risk group with a median survival of 32.8 months (95% CI, 26.3 to 38.5 months) with a hazard ratio of 4.6 ( P < .001), far superior to any individual gene predictor or standard clinical characteristics. We found that comutations of both STK11 a...
Survival prediction of stage I lung adenocarcinomas by expression of 10 genes
Journal of Clinical Investigation, 2007
Adenocarcinoma is the predominant histological subtype of lung cancer, the leading cause of cancer deaths in the world. At stage I, the tumor is cured by surgery alone in about 60% of cases. Markers are needed to stratify patients by prognostic outcomes and may help in devising more effective therapies for poor prognosis patients. To achieve this goal, we used an integrated strategy combining meta-analysis of published lung cancer microarray data with expression profiling from an experimental model. The resulting 80-gene model was tested on an independent cohort of patients using RT-PCR, resulting in a 10-gene predictive model that exhibited a prognostic accuracy of approximately 75% in stage I lung adenocarcinoma when tested on 2 additional independent cohorts. Thus, we have identified a predictive signature of limited size that can be analyzed by RT-PCR, a technology that is easy to implement in clinical laboratories.
Prognostic Genomic Predictive Biomarkers for Early-Stage Lung Cancer Patients
The Open Biomarkers Journal, 2021
Aims: Our goal is to find predictive genomic biomarkers in order to identify subgroups of early-stage lung cancer patients that are most likely to benefit from adjuvant chemotherapy with surgery (ACT). Background: Receiving ACT appears to have a better prognosis for more severe early-stage non-small cell lung cancer patients than surgical resection only. However, not all patients benefit from chemotherapy. Objective: Preliminary studies suggest that the application of ACT is associated with a better prognosis for more severe NSCLC patients compared to those who only underwent surgical resection. Given the immense personal and financial costs associated with ACT, finding the patients who are most likely to benefit from ACT is paramount. Thus, the purpose of this research is to utilize gene expression and clinical data from lung cancer patients to find treatment-associated genomic biomarkers. Methods: To investigate the treatment effect, a modified-covariate regularized Cox regression...
Genome-Wide Analysis of Survival in Early-Stage Non-Small-Cell Lung Cancer
Journal of Clinical Oncology, 2009
Lung cancer, of which 85% is non-small-cell (NSCLC), is the leading cause of cancer-related death in the United States. We used genome-wide analysis of tumor tissue to investigate whether single nucleotide polymorphisms (SNPs) in tumors are prognostic factors in early-stage NSCLC.
Somatic Genomics and Clinical Features of Lung Adenocarcinoma: A Retrospective Study
PLoS medicine, 2016
Lung adenocarcinoma (LUAD) is the most common histologic subtype of lung cancer and has a high risk of distant metastasis at every disease stage. We aimed to characterize the genomic landscape of LUAD and identify mutation signatures associated with tumor progression. We performed an integrative genomic analysis, incorporating whole exome sequencing (WES), determination of DNA copy number and DNA methylation, and transcriptome sequencing for 101 LUAD samples from the Environment And Genetics in Lung cancer Etiology (EAGLE) study. We detected driver genes by testing whether the nonsynonymous mutation rate was significantly higher than the background mutation rate and replicated our findings in public datasets with 724 samples. We performed subclonality analysis for mutations based on mutant allele data and copy number alteration data. We also tested the association between mutation signatures and clinical outcomes, including distant metastasis, survival, and tumor grade. We identifie...
A robust prognostic gene expression signature for early stage lung adenocarcinoma
Biomarker research, 2016
Stage I lung adenocarcinoma is usually not treated with adjuvant chemotherapy; however, around half of these patients do not survive 5 years. Therefore, a reliable prognostic biomarker for early stage patients would be critical to identify those most likely to benefit from early additional treatments. Several studies have searched for gene expression prognostic biomarkers for lung adenocarcinoma, but these have not yielded a widely accepted prognosticator. We analyzed gene expression from seven published lung adenocarcinoma cohorts for which we included only stage I and II patients who were not given adjuvant therapy. Seven genes consistently obtained statistical significance in Cox regression for overall survival. The combined signature has a weighted mean hazard ratio of 3.2 in all cohorts and 3.0 (C.I. 1.3-7.4, p < 0.01) in an independent validation cohort and is strongly correlated with previously published signatures of chromosomal instability and cell cycle progression. The...