Development and Validation of a Six-lncRNA Prognostic Signature in Gastric Cancer

Abstract

Background: Gastric cancer (GC) has been a leading cause of cancer-related mortality for many years. It is thought that long noncoding RNAs (lncRNAs) can play a significant role in GC. This study aimed to construct a powerful six-lncRNA signature as a prognostic biomarker for GC patients.Methods: Based on The Cancer Genome Atlas (TCGA), the expression profiles of lncRNAs and the corresponding clinical data of GC patients were obtained. Cox regression and the least absolute shrinkage and selection operator (LASSO) regression model were used to identify the prognostic lncRNA signature. A total of 337 patients were included in the combined dataset (N = 337), which was divided into a training dataset (N= 169) and a test dataset (N = 168). The reliability of the lncRNA prognostic signature was validated in three datasets.Results: A six-lncRNA prognostic signature was constructed to predict the overall survival (OS) of GC patients. The signature had better discriminability than clinical characteristics. The prognostic risk score was as follows: (expression level of RP11-284F21.7×-0.243981) + (expression level of RP11-432J22.2×-0.502378) + (expression level of RP4-584D14.5×-0.447878) + (expression level of AC093850.2×0.261822) + (expression level of AP000695.6 ×0.654318) + (expression level of AC098973.2× 0.406603). In addition, the signature was confirmed to be a significant predictor for predicting the OS. The nomogram model precisely predicted the OS of GC. Enrichment analysis indicated that the signature was mainly enriched for extracellular matrix-related functions and tumor signaling pathways. The target genes IGFBP7, VCAN, and COL1A1 had prognostic value in GC. AC098973.2 and RP11-284F21.7 was verified for the first time in GC tissues and cell lines.Conclusions: The six-lncRNA prognostic signature could predict the OS and has high clinical application value in GC.