CLDN18: Clinical, Pathological, and Genetic Signatures with Drug Screening in Gastric Adenocarcinoma

Title:CLDN18: Clinical, Pathological, and Genetic Signatures with Drug Screening in Gastric Adenocarcinoma

Volume: 31

Author(s): Joon Young Hur, Kyueng-Whan Min*, Yung-Kyun Noh, Young-Woong Won, Yoomi Yeo, Dong-Hoon Kim, Byoung Kwan Son, Mi Jung Kwon and Jung Soo Pyo

Affiliation:

• Department of Pathology, Uijeongbu Eulji Medical Center, Eulji University School of Medicine, Uijeongbu, Gyeonggi-do, Republic of Korea

Abstract: Introduction: The CLDN18 gene, encoding claudin 18.1 and claudin 18.2, is a key component of tight junction strands in epithelial cells that form a paracellular barrier that is critical in Stomach Adenocarcinoma (STAD).

Methods: Our study included 1,095 patients with proven STAD, 415 from The Cancer Genome Atlas (TCGA) cohort and 680 from the Gene Expression Omnibus database. We applied various analyses, including gene set enrichment analysis, pathway analysis, and in vitro drug screening to evaluate survival, immune cells, and genes and gene sets associated with cancer progression, based on CLDN18 expression levels. Gradient boosting machine learning (70% for training, 15% for validation, and 15% for testing) was used to evaluate the impact of CLDN18 on survival and develop a survival prediction model.

Results: High CLDN18 expression correlated with worse survival in lymphocyte-poor STAD, accompanied by decreased helper T cells, altered metabolic genes, low necrosis-related gene expression, and increased tumor proliferation. CLDN18 expression showed associations with gene sets associated with various stomach, breast, ovarian, and esophageal cancers, while pathway analysis linked CLDN18 to immunity. Incorporating CLDN18 expression improved survival prediction in a machine learning model. Notably, nutlin-3a and niraparib effectively inhibited high CLDN18-expressing gastric cancer cells in drug screening.

Conclusion: Our study provides a comprehensive understanding of the biological role of CLDN18-based bioinformatics and machine learning analysis in STAD, shedding light on its prognostic significance and potential therapeutic implications. To fully elucidate the molecular intricacies of CLDN18, further investigation is warranted, particularly through in vitro and in vivo studies.

Cite this article as:

Hur Young Joon, Min Kyueng-Whan*, Noh Yung-Kyun, Won Young-Woong, Yeo Yoomi, Kim Dong-Hoon, Son Kwan Byoung, Kwon Jung Mi and Pyo Jung Soo, CLDN18: Clinical, Pathological, and Genetic Signatures with Drug Screening in Gastric Adenocarcinoma, Current Medicinal Chemistry 2024; 31 () . https://dx.doi.org/10.2174/0109298673288604240408065715

DOI https://dx.doi.org/10.2174/0109298673288604240408065715	Print ISSN 0929-8673
Publisher Name Bentham Science Publisher	Online ISSN 1875-533X