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Comprehensive bioinformatic analysis reveals TRPM4 as a biomarker for pan-cancer progression and macrophage
Xu Huang1,2, Mingyang Hong3, Ling Gu4
1Nantong Institute of Genetics and Reproductive Medicine, Affiliated Maternity and Child Health Care Hospital of Nantong University, Nantong, 226018, Jiangsu, China.
Background:
Ion channels play key regulatory roles in cancer pathophysiology. They are also considered promising therapeutic targets. The transient receptor potential melastatin 4 (TRPM4) is a nonselective monovalent cation channel, recently identified as critical in necrosis by sodium overload. Multiple studies have demonstrated that this gene is a potential player in cancer biology; however, its comprehensive role in various cancer types remains largely unexplored.
Methods:
In this study, we conducted a comprehensive bioinformatics analysis of TRPM4 across multiple cancer types, examining its expression patterns, prognostic significance, and clinical relevance. We investigated epigenetic modifications, the DNA damage repair response, as well as alternative splicing and intronic polyadenylation associated with TRPM4. In addition, we analyzed signaling pathways related to tumorigenesis and immune responses, alongside assessing immune cell infiltration in tumor microenvironments.
Results:
We systematically delineate the expression heterogeneity of TRPM4 across pan-cancer and its clinical implications: it acts as a risk factor indicating poor prognosis in ACC, LGG, PAAD, MESO, and UVM, whereas it exhibits a protective role in KIRP and UCEC. Mechanistically, TRPM4 is involved not only in epigenetic regulation and DNA damage repair responses but also modulates post-transcriptional processes such as alternative splicing and intronic polyadenylation. Furthermore, TRPM4 expression is significantly associated with multiple tumor-related signaling pathways and immunomodulatory molecules. More importantly, through tumor microenvironment infiltration analysis, we observed spatial co-localization of TRPM4 with CD68⁺ tumor-associated macrophages, suggesting that TRPM4 may exert a potential immunomodulatory function by shaping the tumor immune microenvironment through influencing immune cell infiltration.
Conclusion:
Our research highlights TRPM4 as a promising biomarker and a therapeutic target for cancer treatment. Future investigations should focus on elucidating the mechanistic role of TRPM4 in modulating immune response and tumor progression, potentially paving the way for innovative therapeutic strategies in oncology.
Insights
The transient receptor potential melastatin 4 (TRPM4) channel is a key player in cancer, acting as a prognostic biomarker and potential therapeutic target. Its role in immune cell infiltration suggests a function in shaping the tumor microenvironment.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Ion channels are crucial in cancer pathophysiology and represent promising therapeutic targets.
- Transient receptor potential melastatin 4 (TRPM4) is a cation channel implicated in necrosis and potentially cancer biology.
- The comprehensive role of TRPM4 across diverse cancer types remains largely uninvestigated.
Purpose of the Study:
- To conduct a comprehensive bioinformatics analysis of TRPM4 expression, prognostic significance, and clinical relevance across multiple cancer types.
- To investigate the mechanistic roles of TRPM4 in epigenetic modifications, DNA damage repair, and post-transcriptional processes.
- To explore the association of TRPM4 with tumor-related signaling pathways, immune responses, and tumor microenvironment.
Main Methods:
- Pan-cancer bioinformatics analysis of TRPM4 expression and clinical data.
- Investigation of epigenetic alterations, DNA damage repair, alternative splicing, and intronic polyadenylation related to TRPM4.
- Analysis of TRPM4 association with signaling pathways, immunomodulatory molecules, and immune cell infiltration.
Main Results:
- TRPM4 exhibits heterogeneous expression across cancers, serving as a poor prognostic factor in ACC, LGG, PAAD, MESO, and UVM, but a protective factor in KIRP and UCEC.
- TRPM4 is implicated in epigenetic regulation, DNA damage repair, alternative splicing, and intronic polyadenylation.
- TRPM4 expression correlates with tumor signaling pathways and immune molecules, and co-localizes with tumor-associated macrophages, suggesting immunomodulatory functions.
Conclusions:
- TRPM4 is a potential biomarker and therapeutic target in cancer treatment.
- Further research into TRPM4's role in immune response modulation and tumor progression is warranted.
- TRPM4 may offer novel therapeutic strategies in oncology by influencing the tumor immune microenvironment.
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