Identiﬁcation of TRPM2 as a Potential Therapeutic Target Associated with Immune Infiltration: A Comprehensive Pan-Cancer Analysis and Experimental Veriﬁcation in Ovarian Cancer

Sep 24, 2026

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The exact role of Transient receptor potential melastatin 2 (TRPM2) in tumor progression and immunomodulation remains elusive. This study evaluates TRPM2 expression, diagnostic value, prognostic significance, and genetic/epigenetic alterations across pan-cancer, then connects TRPM2-associated pathways with immune-related signatures. Ovarian cancer specimens and OV cell models verify TRPM2 at mRNA and protein levels. TRPM2 links to unfavorable survival, immunosuppressive microenvironment features, macrophage infiltration, immune checkpoints, and CD206. TRPM2 knockdown reduces proliferation while promoting apoptosis, supporting biomarker and therapeutic potential, especially in ovarian cancer.

LanguageEnglish

CategoryResearch & Report

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Pages21

Reading Time53 min

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Abstract

Introduction

Tumor microenvironment and immunotherapy challenges

TRP channels and the role of TRPM2

Article Identiﬁcation of TRPM2 as a Potential Therapeutic Target Associated with Immune Inﬁltration: A Comprehensive Pan-Cancer Analysis and Experimental Veriﬁcation in Ovarian Cancer Danxi Zheng 1,2, Siyu Long 3 and Mingrong Xi 1, * Citation: Zheng, D.; Long, S.; Xi, M. Identiﬁcation of TRPM2 as a Potential Therapeutic Target Associated with Immune Inﬁltration: A Comprehensive Pan-Cancer Analysis and Experimental Veriﬁcation in Ovarian Cancer. Int. J. Mol. Sci. 2023, 24, 11912. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ijms241511912 Academic Editor: Kentaro Nakayama Received: 20 June 2023 Revised: 13 July 2023 Accepted: 19 July 2023 Published: 25 July 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, No. 20, Third Section of People's South Road, Chengdu 610041, China; [2015181622064@stu.scu.edu.cn](2015181622064@stu.scu.edu.cn) 2 Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Chengdu 610041, China 3 Laboratory of Molecular Translational Medicine, Center for Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, West China Second Hospital, Sichuan University, Chengdu 610041, China; [siyulong0109@alu.scu.edu.cn](siyulong0109@alu.scu.edu.cn) * Correspondence: [xmrjzz@126.com](xmrjzz@126.com) Abstract: The exact role of Transient receptor potential melastatin 2 (TRPM2) in tumor progression and immunomodulation remains elusive. We comprehensively investigated the expression pattern, diagnostic value, prognostic impact, genetic and epigenetic alterations of TRPM2 in pan-cancer. Then, we explored underlying pathways associated with TRPM2 and immune-related signatures. Ovarian cancer (OV) specimens were enrolled to test the expression of TRPM2 by immunohistochemistry and RT-qPCR. OV cell A2780 transfected with shRNA targeting TRPM2 was used in subsequent experiments. TRPM2 was aberrantly expressed and associated with unfavorable prognosis across various cancers. It possesses significant diagnostic values with AUC > 0.90 . TRPM2 participated in pathways mediating immunoregulation and tumorigenesis. The expression of TRPM2 was significantly correlated with tumor microenvironment scores, tumor-stemness index, macrophages infiltration, immune checkpoints, and immune-related genes. OV single-cell datasets also indicated that TRPM2 was predominantly distributed on macrophages and malignancies. The overexpressed TRPM2 in OV tissues was validated at both the mRNA and protein levels. TRPM2 expression was significantly correlated with type2 macrophage marker CD206 . Knockdown of TRPM2 inhibited OV cell proliferation and promoted apoptosis. Overall, TRPM2 has relevance to an immunosuppressive tumor microenvironment by modulating macrophage. It could serve as a powerful biomarker for tumor screening and prognosis, and a potential therapeutic target for tumor treatment, especially for OV. Keywords: TRPM2; pan-cancer; immune inﬁltration; tumor-associated macrophages; ovarian cancer; targeted therapy; immunotherapy 1. Introduction Nowadays, the incidence of cancer is increasing and cancer has become a leading cause of death worldwide, which imposes an enormous health and economic burden on the global healthcare system [1] . The successful clinical application of immunotherapy in some cancer types has subverted the landscape of traditional cancer treatment and Immunotherapy with immune checkpoint inhibitors (ICIs) constitutes a milestone in the advancement of cancer therapy [2,3

FAQs

What is the main goal of this study on TRPM2 in cancer?

To clarify how TRPM2 relates to tumor progression and immunomodulation, and to assess its potential as a diagnostic/prognostic biomarker and therapeutic target, especially in ovarian cancer.

How was TRPM2 expression validated in ovarian cancer?

TRPM2 was measured in ovarian cancer (OV) specimens using immunohistochemistry and RT-qPCR, and in OV cell experiments using shRNA-mediated TRPM2 knockdown.

What effects does TRPM2 knockdown have on ovarian cancer cells?

Knockdown of TRPM2 inhibits OV cell proliferation and promotes apoptosis.

Sep 24, 2026

Upload by Sarah