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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1494131
This article is part of the Research Topic Multi-omics Application in Exploring Potential Biomarkers Targeting Resistance of Anti-Cancer Drugs View all 18 articles

Pan-cancer analysis of CLDN18.2 shed new insights on the targeted therapy of upper gastrointestinal tract cancers

Provisionally accepted
Jun Wu Jun Wu 1,2Yongqiang Zheng Yongqiang Zheng 2Haojie Chen Haojie Chen 2Jinghua Lu Jinghua Lu 1Qiuyue Chen Qiuyue Chen 1Minggang Cheng Minggang Cheng 1Ze-xian Liu Ze-xian Liu 2*
  • 1 Baoan Clinical Medical School, Guangdong Medical University, Shenzhen, Guangdong, China
  • 2 Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, China

The final, formatted version of the article will be published soon.

    Background: CLDN18.2 is a widely researched drug target. However, previous research has primarily been based on immunohistochemistry results and focused on gastric cancer.To analyze the potential cancer-targeting effect of CLDN18.2 from a multi-omics perspective, this study quantified CLDN18.2 expression in The Cancer Genome Atlas (TCGA) pan-cancer cohort. Thus, the relationships between CLDN18.2 expression and genomic alterations, immune infiltration, and prognosis were analyzed. Additionally, we performed analyses of the differentially expressed genes and enriched pathways between the high-and low-CLDN18.2 expression groups, as well as the corresponding drug sensitivity analyses.The results indicated that CLDN18.2 was highly expressed in pancreatic adenocarcinoma (PAAD), stomach adenocarcinoma (STAD), colorectal cancer (CRC), and esophageal carcinoma (ESCA). Moreover, the high-and low-CLDN18.2 expression groups presented significant differences in terms of genomic alterations and immune infiltration, such as the levels of methylation and CD4 + T cell infiltration. Furthermore, high CLDN18.2 expression was significantly associated with poor prognosis in bladder urothelial carcinoma (BLCA), ESCA and PAAD. In upper gastrointestinal tract cancers (STAD, ESCA, and PAAD), downregulated gene-enriched pathways were associated with cell signaling, whereas upregulated gene-enriched pathways were associated with angiogenesis. Finally, we identified drugs associated with CLDN18.2 expression to which samples with different levels of expression were differentially sensitive.CLDN18.2 was highly expressed in upper gastrointestinal tract cancers and its expression had a significant effect on genomic alterations and the tumor microenvironment. Additionally, low CLDN18.2 expression was linked to favorable prognosis. Our study reveals the potential value of CLDN18.2 for tumor prognosis and targeted therapy in various cancers, especially upper gastrointestinal tract cancers.

    Keywords: CLDN18.2, Alternative splicing events, upper gastrointestinal tract cancers, prognosis, drug sensitivity

    Received: 10 Sep 2024; Accepted: 14 Oct 2024.

    Copyright: © 2024 Wu, Zheng, Chen, Lu, Chen, Cheng and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor 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.

    * Correspondence: Ze-xian Liu, Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.