Identification and Verification of Potential Biomarkers in Gastric Cancer By Integrated Bioinformatic Analysis

Chenyu Sun, Yue Chen, Na Hyun Kim, Scott Lowe, Shaodi Ma, Zhen Zhou, Rachel Bentley, Yi Sheng Chen, Margarita Whitaker Tuason, Wenchao Gu, Chandur Bhan, John Pocholo Whitaker Tuason, Pratikshya Thapa, Ce Cheng, Qin Zhou, Yanzhe Zhu

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Abstract

Background: Gastric cancer (GC) is a common cancer with high mortality. This study aimed to identify its differentially expressed genes (DEGs) using bioinformatics methods. Methods: DEGs were screened from four GEO (Gene Expression Omnibus) gene expression profiles. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. A protein–protein interaction (PPI) network was constructed. Expression and prognosis were assessed. Meta-analysis was conducted to further validate prognosis. The receiver operating characteristic curve (ROC) was analyzed to identify diagnostic markers, and a nomogram was developed. Exploration of drugs and immune cell infiltration analysis were conducted. Results: Nine up-regulated and three down-regulated hub genes were identified, with close relations to gastric functions, extracellular activities, and structures. Overexpressed Collagen Type VIII Alpha 1 Chain (COL8A1), Collagen Type X Alpha 1 Chain (COL10A1), Collagen Triple Helix Repeat Containing 1 (CTHRC1), and Fibroblast Activation Protein (FAP) correlated with poor prognosis. The area under the curve (AUC) of ADAM Metallopeptidase With Thrombospondin Type 1 Motif 2 (ADAMTS2), COL10A1, Collagen Type XI Alpha 1 Chain (COL11A1), and CTHRC1 was >0.9. A nomogram model based on CTHRC1 was developed. Infiltration of macrophages, neutrophils, and dendritic cells positively correlated with COL8A1, COL10A1, CTHRC1, and FAP. Meta-analysis confirmed poor prognosis of overexpressed CTHRC1. Conclusion: ADAMTS2, COL10A1, COL11A1, and CTHRC1 have diagnostic values in GC. COL8A1, COL10A1, CTHRC1, and FAP correlated with worse prognosis, showing prognostic and therapeutic values. The immune cell infiltration needs further investigations.

Original languageEnglish
Article number911740
Number of pages17
JournalFrontiers in Genetics
Volume13
DOIs
Publication statusPublished - 15 Jul 2022
Externally publishedYes

Keywords

  • bioinformatics analysis
  • gastric cancer
  • hub genes
  • immune infiltration
  • meta-analysis
  • prognostic value
  • ROC (receiver operating curve)

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