Table 3_Integrate single-cell and transcriptome analyses to explore the prognostic genes related to TRPM4 in bladder cancer.xlsx

Bladder cancer (BLCA) is a common malignancy of the urinary system, yet the therapeutic relevance of transient receptor potential cation channel subfamily M member 4 (TRPM4) remains unclear. By integrating single-cell and whole-genome transcriptomic data, this study revealed significant transient receptor potential cation channel subfamily M member 4 (TRPM4) overexpression in bladder cancer (BLCA) (p < 0.05), particularly in epithelial cells. Intersection analysis identified 220 candidate genes (7,808 DEGs1, 4,683 DEGs2, and 4,802 key cell module genes). A risk model was constructed comprising six screened prognostic marker genes, namely, protein unc-93 homolog B1 (UNC93B1), family with sequence similarity 193 member B (FAM193B), protein O-glucosyltransferase (POGLUT3), fibrillin-1 (FBN1), microtubule-associated protein 1B (MAP1B), and RUNX family transcription factor 2 (RUNX2). The model demonstrated marked differences among the risk groups. Gene set enrichment analysis revealed significant disparities in key pathways, including the melanoma pathway (p < 0.05). Furthermore, immune infiltration analysis has identified 12 distinct immune cell types, including naive B cells, which showed a p < 0.05 distribution. The observed distribution was uneven. In the drug sensitivity analysis, 112 drugs (including WZ3105; p < 0.05) showed differential responses, and UNC93B1 showed high positive expression in BLCA tissues (positive cell proportion > 75%). Our studies confirmed that TRPM4 has significant prognostic value and is a potential novel diagnostic and therapeutic target for BLCA.

膀胱癌（Bladder cancer, BLCA）是泌尿系统常见的恶性肿瘤，但其瞬时受体电位阳离子通道亚家族M成员4（transient receptor potential cation channel subfamily M member 4, TRPM4）的治疗相关性仍未明确。本研究整合单细胞及全基因组转录组数据，发现膀胱癌组织中存在显著的TRPM4过表达（p < 0.05），且该过表达主要富集于上皮细胞中。通过交集分析共筛选出220个候选基因，其中包含7808个差异表达基因1（DEGs1）、4683个差异表达基因2（DEGs2）以及4802个核心细胞模块基因。本研究构建了包含6个经筛选的预后标志物基因的风险模型，分别为unc-93同源物B1（protein unc-93 homolog B1, UNC93B1）、序列相似性家族193成员B（family with sequence similarity 193 member B, FAM193B）、蛋白O-葡萄糖基转移酶3（protein O-glucosyltransferase 3, POGLUT3）、原纤维蛋白1（fibrillin-1, FBN1）、微管相关蛋白1B（microtubule-associated protein 1B, MAP1B）以及RUNX家族转录因子2（RUNX family transcription factor 2, RUNX2）。该风险模型在不同风险分组中表现出显著的区分度。基因集富集分析显示，包括黑色素瘤通路在内的关键通路存在显著表达差异（p < 0.05）。此外，免疫浸润分析共鉴定出12种不同的免疫细胞类型，其中初始B细胞（naive B cells）的分布差异具有统计学意义（p < 0.05），且整体免疫细胞分布并不均匀。在药物敏感性分析中，共发现112种药物（包括WZ3105；p < 0.05）在样本中表现出差异性响应；同时，UNC93B1在膀胱癌组织中呈现高阳性表达（阳性细胞占比>75%）。本研究证实，TRPM4具有显著的预后价值，有望成为膀胱癌潜在的新型诊断与治疗靶点。