Identification of New Therapeutic Targets for Gastric Cancer With Bioinformatics.

Yang Li,Le-Ping Li,Tao Zhang,Hong-Chang Wang,Jin-Shen Wang

doi:10.3389/fgene.2020.00865

Yang Li, Le-Ping Li + Show 3 more

Open Access

https://doi.org/10.3389/fgene.2020.00865

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Abstract

We aimed to identify new targets affecting gastric cancer (GC) prognosis. Six target genes were identified from hub genes based on their relationship with important factors affecting tumor progression, like immune infiltration, purity, tumor mutation burden (TMB), and tumor microenvironment (TME) score. The effect of target genes’ somatic mutations and copy number alteration (CNA) was examined to determine their effect on GC prognosis. Six target genes (FBN1, FN1, HGF, MMP9, THBS1, and VCAN) were identified. Reduced expression of each target gene, except MMP9, indicated better prognosis and lower grade in GC. FBN1, THBS1, and VCAN showed lower expression in stage I GC. Non-silencing mutations of the six genes played a role in significantly higher TMB and TME scores. THBS1 mutation was associated with earlier stage GC, and VCAN mutation was associated with lower grade GC. However, patients with target gene CNA displayed higher tumor purity. MMP9, THBS1, and VCAN CNA was associated with lower grade GC, while FBN1 CNA reflected earlier T stage. Additionally, the target genes may affect GC prognosis by influencing multiple oncogenic signaling pathways. FBN1, FN1, HGF, MMP9, THBS1, and VCAN may be new GC prognostic targets by affecting tumor purity, TMB, TME score, and multiple oncogenic signaling pathways.

Highlights

Gastric cancer (GC) is a disease with a high incidence and high mortality around the world (Kamangar et al, 2006)
RNA-seq data from gastric cells was downloaded from the Cell Line Encyclopedia (CCLE) database1. 5-FU and oxaliplatin drug sensitivity for different gastric cancer cell lines were obtained from the Genomics of Drug Sensitivity in Cancer (GDSC) database2
Gene Ontology Biological process (GO-BP) analysis showed that the differentially expressed genes were primarily involved in negative regulation of endopeptidase activity, cell adhesion, inflammatory response, and O-glycan processing (Figures 2C,D)

Summary

Introduction

Gastric cancer (GC) is a disease with a high incidence and high mortality around the world (Kamangar et al, 2006). With the development of medical technology, treatment of GC with surgery combined with chemoradiotherapy is gradually becoming more effective, but the 5year survival rate remains subpar (Ferlay et al, 2015; Li Y. et al, 2019). Postoperative chemotherapy has a major impact on the prognosis and survival of GC patients. New Therapeutic Targets of GC (Kunkler, 1994; van de Velde, 2008; Bernini and Bencini, 2012). A variety of regimens have been studied to identify an improved therapeutic approach. Treatment can vary greatly in patients with the same pathological type and stage, or even in those with similar expression of hub genes (Yan et al, 2018; Huang et al, 2019). It is important to identify new targets influencing the prognosis of GC

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