Genome-wide analysis to identify a novel microRNA signature that predicts survival in patients with stomach adenocarcinoma

Abstract

Objective: Using genome-wide screening, this study was aimed at identifying prognostic microRNA (miRNA) in those patients suffering from stomach adenocarcinoma (STAD). Methods: A genome-wide miRNA sequencing dataset and relevant STAD clinical information was obtained via The Cancer Genome Atlas (TCGA). Prognostic miRNA selection was carried out through a whole genome multivariate Cox regression model in order to establish a prognostic STAD signature. Results: Eleven miRNAs (hsa-mir-509-2, hsa-mir-3917, hsa-mir-495, hsa-mir-653, hsa-mir-3605, hsa-mir-2115, hsa-mir-1292, hsa-mir-137, hsa-mir-6511b-1, hsa-mir-145, and hsa-mir-138-2) were recognized as prognostic and used for the construction of a STAD prognostic signature. This signature exhibited good performance in predicting prognosis (adjusted P<0.0001, adjusted hazard ratio= 3.047, and 95% confidence interval=2.148-4.323). The time-dependent receiver operating characteristic examination exhibited area under curve values of 0.711, 0.697, 0.716, 0.733, 0.805, and 0.805, for 1-, 2-, 3-, 4-, 5-, and 10-year overall survival (OS) estimation, respectively. Comprehensive survival analysis suggests that the 11-miRNA prognostic signature acts as an independent feature of STAD prognosis and exhibits superior performance in OS prediction when compared to traditional clinical parameters. Furthermore, fourteen miRNA target genes were linked to STAD OS. These included SERPINE1, MLEC,

MicroRNA-653-5p Promotes Gastric Cancer Proliferation and Metastasis by Targeting the SOCS6-STAT3 Pathway

“…Furthermore, previous studies only discussed the function and expression of miR-653-5p under the regulation of long non-coding RNA or circular RNA. Moreover, Luo et al (2019) reported that an 11-miRNA expression signature including miR-653 was as an independent predictor of poor prognosis, and was an excellent predictor of overall survival. Importantly, this study strongly suggested that miR-653-5p promoted GC cell proliferation and metastasis both in vitro and in vivo, which indicates miR-653-5p may play an important role in GC progression.…”

Multivariate gene expression‐based survival predictor model in esophageal adenocarcinoma

“…30 It contributes to ibrutinib resistance of diffuse large B-cell lymphoma through EGFR activation 60 and also the prognosis of gastric adenocarcinoma patients. 61 There have been many efforts to identify biomarkers for EAC prognosis. Lan et al reported a six miRNA signature of esophageal adenocarcinoma in 2019.…”

“…PDFD‐D plays an important role in cell proliferation, apoptosis, transformation, invasion, metastasis, angiogenesis and other biological processes, 59 and its downregulation expression has been reported to inhibit the NF‐κB pathway for cell proliferation and invasion, and induce apoptosis in esophageal squamous cell carcinoma 30 . It contributes to ibrutinib resistance of diffuse large B‐cell lymphoma through EGFR activation 60 and also the prognosis of gastric adenocarcinoma patients 61 …”

Predicting Associations of miRNAs and Candidate Gastric Cancer Genes for Nanomedicine

“…The success in the development of nanomedicine depends on the progress in studying the molecular basis of diseases. Most diseases are caused by the impaired expression of many genes and many miRNAs [ 30 , 31 , 32 , 33 ]. Therefore, to get deeper insights into the molecular basis of diseases, it is necessary to study the regulation of all human genes by all human miRNAs of the expression.…”

“…Gastric cancer (stomach cancer) develops rapidly and, as a rule, even early diagnosis of the disease does not significantly affect the duration of the disease [ 30 ]. Added to this is the lack of effective treatments for gastric cancer.…”