Identification of the key miRNAs associated with survival time in stomach adenocarcinoma

Abstract

Stomach adenocarcinoma (STAD) is one of the leading causes of cancer morbidity and mortality worldwide. The present study aimed to identify the microRNAs associated with STAD survival time. The clinical information and microarray miRNA and mRNA expression profiles of STAD patients were downloaded from The Cancer Genome Atlas. Differential expression (DE) analysis was performed to identify DEmiRNAs and DEmRNAs in STAD. The DEmiRNAs associated with the survival time of patients with STAD were identified through DE analysis, negative correlation pair analysis, miRNA target gene prediction, univariate Cox regression analysis and Kaplan-Meier analysis. The functions of the target genes of the DEmiRNAs were predicted with Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. A total of 355 DEmiRNAs and 1,722 DEmRNAs were identified between STAD and normal tissues. A total of 5 DEmiRNAs were identified to be associated with STAD survival, including 4 risk-associated DEmiRNAs (miR-30a, −143, −145 and −133b) and 1 protective DEmiRNA (miR-135b). The target DEmRNAs were significantly enriched for DNA metabolic process in the biological process GO category, and in KEGG cell cycle signaling pathways. Kaplan-Meier curves indicated that the overall survival time in the miR-30a, −143, −145 and −133b high expression groups was significantly shorter than that in the low expression groups, whereas the survival time was prolonged in the miR-135b high expression group compared with that in the low expression group. Therefore, miR-30a, −143, −145, −133b and −135b may be involved in the tumorigenesis and development of STAD, and may be potential biomarkers for its early diagnosis and prognosis.

miRNome Reveals New Insights Into the Molecular Biology of Field Cancerization in Gastric Cancer

“…Approximately 90% of the miRNA reads (∼8.5 million reads) were concentrated on the 35 most expressed miRNAs. The number and representativity of D. E. expressed miRNAs identified in this study is similar to other studies that performed miRNome analysis (Hou et al, 2011; Maltseva et al, 2014; Liu et al, 2015; Castro-Magdonel et al, 2017; Liang et al, 2017).…”

“…Studies that analyzed the data from miRNA sequencing in gastric cancer demonstrated their deregulation in this type of tumor (Assumpção et al, 2015; Darnet et al, 2015; Liu et al, 2015; Liang et al, 2017). Among the miRNAs found in these studies, hsa-miR-99a , -miR-100 , -miR-133a/b-3p , -miR-135b , -miR-141 , -miR-143 , -miR-145 , -miR-148a , -miR-196a/b , -miR-200a , -miR-218-1 , -miR-215 , and -miR-490 were also observed in the present study.…”

“…Liu et al (2015) analyzed miRNome in gastric cancer downloaded from the TCGA; however, this database basically has samples from European and Asian populations. These authors identified 54 D. E. miRNAs (using the P adj < 0.05 and |log2 ( fold change )| > 3) and two miRNAs ( hsa-miR-133a / b ) were the most D. E. Liang et al (2017) also analyzed miRNomes in GC using samples from the same database (TCGA) and identified 43 D. E. miRNAs (using the FDR < 0.001 and | log2 ( fold change )| > 1.5); of these, 5 miRNAs (hsa-miR-30a , -miR-135b , -miR-133b , -miR-143 , and -miR-145 ) were associated with patient survival time. We emphasize that the “normal” or “healthy” tissues used in these two studies are of patients with the disease (adjacent to the gastric cancer tissues), since the TCGA does not have expression data of gastric tissues of patients without the history of GC.…”

Prognostic Value and Immune Infiltrates of ABCA8 and FABP4 in Stomach Adenocarcinoma

“…STAD is the second leading cause of cancer-related death due to its poor prognosis [2,3]. The identification of a new valuable prognostic marker for STAD becomes more urgent [23].…”

“…Most patients with STAD are diagnosed at the advanced stage of the disease. The 5-year survival rate of these patients is very low, and the prognosis of STAD remains poor [2,3]. Therefore, it is urgent to identify a new valuable prognostic marker for STAD.…”