Abstract

Gastric cancer (GC) remains the third deadliest malignancy in China. Despite the current understanding that the long noncoding RNAs (lncRNAs) play a pivotal function in the growth and progression of cancer, their prognostic value in GC remains unclear. Therefore, we aimed to construct a polymolecular prediction model by employing a competing endogenous RNA (ceRNA) network signature obtained by integrated bioinformatics analysis to evaluate patient prognosis in GC. Overall, 1,464 mRNAs, 14,376 lncRNAs, and 73 microRNAs (miRNAs) were found to be differentially expressed in GC. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that these differentially expressed RNAs were mostly enriched in neuroactive ligand–receptor interaction, chemical carcinogenesis, epidermis development, and digestion, which were correlated with GC. A ceRNA network consisting of four lncRNAs, 21 miRNAs, and 12 mRNAs were constructed. We identified four lncRNAs (lnc00473, H19, AC079160.1, and AC093866.1) as prognostic biomarkers, and their levels were quantified by qRT-PCR in cancer and adjacent noncancerous tissue specimens. Univariable and multivariable Cox regression analyses suggested statistically significant differences in age, stage, radiotherapy, and risk score groups, which were independent predictors of prognosis. A risk prediction model was created to test whether lncRNAs could be used as an independent risk predictor of GC or not. These novel lncRNAs’ signature independently predicted overall survival in GC (p < 0.001). Taken together, this study identified a ceRNA and protein–protein interaction networks that significantly affect GC, which could be valuable for GC diagnosis and therapy.

Highlights

  • According to global cancer statistics, gastric cancer (GC) represents a major fatal tumor, with an incidence rate of 5.7% and a mortality rate of 8.2% (Bray et al, 2018)

  • 1,464 mRNAs, 14,376 long noncoding RNAs (lncRNAs), and 73 miRNAs with differential expression were identified in Gastric cancer (GC) (Figure 2 and Supplementary Table S4)

  • The lncRNA–miRNA interactions were based on the miRcode algorithm considering the GC-specific miRNAs

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Summary

Introduction

According to global cancer statistics, gastric cancer (GC) represents a major fatal tumor, with an incidence rate of 5.7% and a mortality rate of 8.2% (Bray et al, 2018). GC remains a lifethreatening disease among Chinese individuals due to its high malignancy, low survival rate, and poor prognosis (Chen et al, 2016; Allemani et al, 2018; Bray et al, 2018). Despite recent technical and medical advances, overall survival (OS) in GC remains low, owing to its detection at the advanced stages of proliferation. Lnc00473 significantly affects tumor promotion in multiple cancers, with obvious roles in GC cell growth, adhesion, and migration. High expression of the lncRNA H19 can promote GC occurrence and metastasis, while p53 may determine H19 elevation in hypoxic cancer cells (Matouk et al, 2010; Zhou et al, 2015a). Accessibility, noninvasive detection, and abnormal expression under different pathophysiological conditions, lncRNAs are considered to be a potential marker for GC diagnosis, prognosis, and potential therapeutic target in this malignancy

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