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

TITLE=Identification of New Therapeutic Targets for Gastric Cancer With Bioinformatics

JOURNAL=Frontiers in Genetics

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2020.00865

DOI=10.3389/fgene.2020.00865

ISSN=1664-8021

ABSTRACT=<p>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 (<italic>FBN1</italic>, <italic>FN1, HGF, MMP9, THBS1</italic>, and <italic>VCAN</italic>) were identified. Reduced expression of each target gene, except <italic>MMP9</italic>, indicated better prognosis and lower grade in GC. <italic>FBN1, THBS1</italic>, and <italic>VCAN</italic> showed lower expression in stage I GC. Non-silencing mutations of the six genes played a role in significantly higher TMB and TME scores. <italic>THBS1</italic> mutation was associated with earlier stage GC, and <italic>VCAN</italic> mutation was associated with lower grade GC. However, patients with target gene CNA displayed higher tumor purity. <italic>MMP9</italic>, <italic>THBS1</italic>, and <italic>VCAN</italic> CNA was associated with lower grade GC, while <italic>FBN1</italic> CNA reflected earlier T stage. Additionally, the target genes may affect GC prognosis by influencing multiple oncogenic signaling pathways. <italic>FBN1, FN1, HGF, MMP9, THBS1</italic>, and <italic>VCAN</italic> may be new GC prognostic targets by affecting tumor purity, TMB, TME score, and multiple oncogenic signaling pathways.</p>