Discover. Oncology最新文献

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.

Mesenchymal Stromal Cells (MSCs) and pericytes, although a minor cellular component of the tumor microenvironment (TME), exert outsized control over cancer progression, metastasis, and therapeutic response across both solid and hematologic malignancies. Once separated by functional and anatomical criteria, Single-cell RNA sequencing (scRNA seq) analyses and context-dependent phenotypic transitions - pericyte-to Cancer-Associated Fibroblasts (CAFs) and MSCs-to-CAFs, now blur these classical distinctions, revealing fluid entities and substantial functional convergence. We synthesize current evidence showing that MSCs and pericytes frequently adopt overlapping pro-angiogenic, immunosuppressive, and pro-invasive states driven by PDGF-B/PDGFRβ, TGF-β, CXCL12, and Notch/ROCK signaling. Across cancers, their roles are multifaceted: in Colorectal Cancer (CRC) from neo-vascularization and Drug Resistance (DR) to blood vessel formation, invasion, and metastatic spread. Moreover, MSCs reinforce immunosuppression, whereas pericyte phenotype switching may sensitize tumors to immunotherapy, thus playing a pivotal role in fibrosis-driven cancer progression. In hematologic malignancies, particularly in the Bone Marrow (BM) niche, MSCs sustain leukemic cell survival and DR. Shared markers and transcriptomic signatures, coupled with striking plasticity, underscore their central role in shaping a pro-tumorigenic milieu. This convergence helps to explain the limits of current approaches-such as anti-VEGF monotherapy and supports new strategies. Enhancing pericyte maturity or intercepting transitions toward CAFs are promising avenues to boost treatment efficacy. We propose a practical framework for classifying "MSC-pericyte states" in the TME and emphasize rigorous, multi-marker, spatially resolved analyses to dissect their complex functions, thus opening a new scenario for targeted therapies.