Abstract
Recent microRNA (miRNA) expression profiling studies suggest the clinical use of miRNAs as potential prognostic biomarkers in various malignancies. In this study, aiming to identify microRNAs with prognostic value for overall survival (OS) in stomach adenocarcinoma (STAD) patients, we analyzed the miRNA expression profiles and the associated clinical characteristics in 380 STAD samples from The Cancer Genome Atlas (TCGA) dataset. An eight-miRNA signature for predicting OS in STAD patients was identified and self-validated by survival analysis and semi-supervised principal components method. We developed a linear prognostic model composed of these miRNAs to divide patients into high- and low-risk groups according to the calculated prognostic scores. Kaplan-Meier analysis demonstrated that patients in the high-risk group had worse OS compared with patients in the low-risk group. Notably, this miRNA prognostic model showed prognostic significance to the STAD patients in early stages and the chemo-resistant patients, who would potentially benefit from additional medical interventions. Finally, this eight-miRNA signature is an independent prognostic biomarker and demonstrates a good predictive performance for 5-year survival. Thus, this signature may serve as a novel biomarker for predicting survival as well as chemotherapy response in STAD patients.
Highlights
Gastric cancer (GC) represents a major health problem worldwide, ranking the fifth most common malignancy and the third leading cause of global cancer mortality [1]
Expressed miRNAs in stomach adenocarcinoma (STAD) versus paired adjacent normal tissue After filtering out unqualified cases, miRNA expression and clinical data of 380 STAD patients were retained for survival analysis
We found 138 miRNAs were differentially expressed between STAD and adjacent normal tissues, among which 17 miRNAs levels were associated with at least two of following histopathological factors: T stage, lymph www.impactjournals.com/oncotarget node metastasis, distant metastasis and tumor grade
Summary
Gastric cancer (GC) represents a major health problem worldwide, ranking the fifth most common malignancy and the third leading cause of global cancer mortality [1]. It is essential to discover specific prognostic factors that may help guide the clinical therapeutic implications and improve the overall survival (OS) for these patients. Due to the stability and expression specificity of miRNAs in different tissues, there is increasing evidence to suggest that they can serve as novel prognostic biomarkers with potential clinical significance for various cancer types. A number of miRNAs were further proposed to be potential prognostic biomarkers for outcomes of GC patients, such as miR-20b, miR-150, miR-214, miR-375, Let-7g, miR-125-5p, miR-146a, miR-218, miR-433, miR-451 and miR-200b/c [6, 12,13,14] [15,16,17,18,19]. Besides the limitations in the dynamic range, sensitivity, and specificity of the microarray data themselves, different technological detection platforms, small sample size, various methods employed for data processing and analysis may result in significant variations
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