Li Shi, Tian Ye, Sun Yu, Xu Tian, Wang Wei
Department of Urology, Central Hospital of Dalian University of Technology, Dalian, China.
Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Cell Oncol (Dordr). 2025 Aug 19. doi: 10.1007/s13402-025-01099-w.
Advanced prostate cancer (PCa) displays significant genetic heterogeneity and therapy resistance, yet the role of sensory perception pathways in its progression remains unclear.
We performed an integrative multi-omics analysis of sensory perception-linked mRNAs and lncRNAs from TCGA and scRNA-seq data. Unsupervised consensus clustering defined three molecular subtypes (CS1-CS3). Key biomarkers were validated in patient tissues and serum. Immune and stromal infiltration were quantified using TIDE and ESTIMATE. Single-cell trajectories characterized TSC22D3-positive T cells, and NicheNet mapped ligand-receptor interactions.
Three subtypes emerged, with CS1 showing the poorest prognosis, marked chemotherapy resistance, and pronounced stromal-immune crosstalk. CS1 tumors exhibited elevated B- and T-cell infiltration and increased oxidative phosphorylation in TSC22D3-positive T cells. NicheNet analysis identified the TNF-CCL20 axis as a central mediator of immunosuppressive signaling and chemoresistance in CS1.
This study establishes sensory perception-associated molecular subtypes in PCa and links CS1 chemoresistance to immune microenvironment reprogramming via TNF-CCL20 signaling. These findings offer mechanistic insights into PCa progression and suggest actionable targets to overcome therapeutic resistance.
晚期前列腺癌（PCa）表现出显著的基因异质性和治疗抗性，然而感觉感知通路在其进展中的作用仍不清楚。
我们对来自TCGA和scRNA-seq数据的与感觉感知相关的mRNA和lncRNA进行了综合多组学分析。无监督一致性聚类定义了三种分子亚型（CS1-CS3）。关键生物标志物在患者组织和血清中得到验证。使用TIDE和ESTIMATE对免疫和基质浸润进行定量。单细胞轨迹表征了TSC22D3阳性T细胞，NicheNet绘制了配体-受体相互作用。
出现了三种亚型，CS1预后最差，具有明显的化疗抗性和显著的基质-免疫串扰。CS1肿瘤表现出B细胞和T细胞浸润增加，以及TSC22D3阳性T细胞中氧化磷酸化增加。NicheNet分析确定TNF-CCL20轴为CS1中免疫抑制信号和化疗抗性的中心介质。
本研究在PCa中建立了与感觉感知相关的分子亚型，并将CS1化疗抗性与通过TNF-CCL20信号传导的免疫微环境重编程联系起来。这些发现为PCa进展提供了机制性见解，并提出了克服治疗抗性的可操作靶点。
