Clinical and Translational Research
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Feb 6, 2023; 11(4): 738-755
Published online Feb 6, 2023. doi: 10.12998/wjcc.v11.i4.738
CD93 serves as a potential biomarker of gastric cancer and correlates with the tumor microenvironment
Zheng Li, Xiao-Jie Zhang, Chong-Yuan Sun, He Fei, Ze-Feng Li, Dong-Bing Zhao
Zheng Li, Xiao-Jie Zhang, Chong-Yuan Sun, He Fei, Ze-Feng Li, Dong-Bing Zhao, Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
Author contributions: Li Z and Zhang XJ contributed to the conceptualization; Li Z contributed to the methodology; Sun CY contributed to the software; Li Z and Zhang XJ contributed to the validation; Li Z and Fei H contributed to the formal analysis; Li ZF contributed to the investigation; Zhao DB contributed to the resources; Li Z and Sun CY contributed to the writing-original draft preparation; All authors contributed to the writing-review and editing; Zhao DB contributed to the project administration. All authors have reviewed and agreed to the published version of the manuscript.
Conflict-of-interest statement: All authors declare no conflict of interest.
Data sharing statement: All data analyzed in this study can be available in XENA (http://xena.ucsc.edu), GEO (https://www.ncbi.nlm.nih.gov/geo/).
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Dong-Bing Zhao, MD, Professor, Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Pan-Jia-Yuan South Lane, Chaoyang District, Beijing 100021, China. dbzhao@cicams.ac.cn
Received: October 12, 2022
Peer-review started: October 12, 2022
First decision: December 13, 2022
Revised: December 13, 2022
Accepted: January 3, 2023
Article in press: January 3, 2023
Published online: February 6, 2023
Abstract
BACKGROUND

The tumor microenvironment (TME) plays an important role in the growth and expansion of gastric cancer (GC). Studies have identified that CD93 is involved in abnormal tumor angiogenesis, which may be related to the regulation of the TME.

AIM

To determine the role of CD93 in GC.

METHODS

Transcriptomic data of GC was investigated in a cohort from The Cancer Genome Atlas. Additionally, RNA-seq data sets from Gene Expression Omnibus (GSE118916, GSE52138, GSE79973, GSE19826, and GSE84433) were applied to validate the results. We performed the immune infiltration analyses using ESTIMATE, CIBERSORT, and ssGSEA. Furthermore, weighted gene co-expression network analysis (WGCNA) was conducted to identify the immune-related genes.

RESULTS

Compared to normal tissues, CD93 significantly enriched in tumor tissues (t = 4.669, 95%CI: 0.342-0.863, P < 0.001). Higher expression of CD93 was significantly associated with shorter overall survival (hazard ratio = 1.62, 95%CI: 1.09-2.4, P = 0.017), less proportion of CD8 T and activated natural killer cells in the TME (P < 0.05), and lower tumor mutation burden (t = 4.131, 95%CI: 0.721-0.256, P < 0.001). Genes co-expressed with CD93 were mainly enriched in angiogenesis. Moreover, 11 genes were identified with a strong relationship between CD93 and the immune microenvironment using WGCNA.

CONCLUSION

CD93 is a novel prognostic and diagnostic biomarker for GC, that is closely related to the immune infiltration in the TME. Although this retrospective study was a comprehensive analysis, the prospective cohort studies are preferred to further confirm these conclusions.

Keywords: Gastric cancer, CD93, Tumor microenvironment, Immunotherapy, Prognosis, Biomarker

Core Tip: Gastric cancer (GC) is an aggressive malignancy, with a 5-year survival rate lower than 20%. The disease burden caused by GC remains heavy worldwide. In this study, various analyses were performed using transcriptomic profiles from the Gene Expression Omnibus databases and The Cancer Genome Atlas. Finally, enrichment analysis and protein-protein interaction network were constructed. CD93 is identified as a diagnostic and prognostic biomarker of GC, which is closely related to the immune infiltration in the tumor microenvironment. Then, Immune-related gene modules were identified to further reveal the relationship between CD93 and immune characteristics.