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Identification and verification of potential biomarkers in gastric cancer by integrated bioinformatic analysis

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Sun, C, Chen, Y, Kim, NH, Lowe, S, Ma, S, Zhou, Z ORCID: 0000-0002-0835-8686, Bentley, R, Chen, YS, Whitaker Tuason, M, Gu, W, Bhan, C, Whitaker Tuason, JP, Thapa, P, Cheng, C, Zhou, Q and Zhu, Y 2022 , 'Identification and verification of potential biomarkers in gastric cancer by integrated bioinformatic analysis' , Frontiers in Genetics, vol. 13 , doi: 10.3389/fgene.2022.911740.

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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.

Item Type: Article
Authors/Creators:Sun, C and Chen, Y and Kim, NH and Lowe, S and Ma, S and Zhou, Z and Bentley, R and Chen, YS and Whitaker Tuason, M and Gu, W and Bhan, C and Whitaker Tuason, JP and Thapa, P and Cheng, C and Zhou, Q and Zhu, Y
Keywords: gastric cancer, hub genes, bioinformatics analysis, prognostic value, immune infiltration
Journal or Publication Title: Frontiers in Genetics
Publisher: Frontiers Research Foundation
ISSN: 1664-8021
DOI / ID Number: 10.3389/fgene.2022.911740
Copyright Information:

Copyright © 2022 Sun, Chen, Kim, Lowe, Ma, Zhou, Bentley, Chen, Tuason, Gu, Bhan, Tuason, Thapa, Cheng, Zhou and Zhu. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) License (https://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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