Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
Heterogeneity of cancer-associated fibroblast subtypes in the prostate cancer microenvironment and their clinical implications: prognostic model construction and therapeutic target exploration based on bioinformatics analysis.
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Ma Zifang, Zhou Xun, Tao Xueting, Wen Jian, Chen Yifan, Shen Huilong, Yao Zhijun
Аннотация
BACKGROUND: In prostate cancer (PCa), cancer-associated fibroblasts (CAFs) play a pivotal role, yet their specific mechanisms remain incompletely elucidated.
METHODS: This study analyzed transcriptomic data and clinical information from 948 PCa patients sourced from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Three distinct CAF subtypes (C1, C2, C3) were identified, and their roles in tumor progression and the immune microenvironment were explored.
RESULTS: The results demonstrated significant associations between these CAF subtypes and patient prognosis, tumor microenvironment (TME) characteristics, as well as immune cell infiltration. Notably, the C2 subtype exhibited the strongest immune infiltration capacity and highest expression of CAF-related genes, correlating with poor prognosis and marked features of immune evasion. In-depth analysis revealed that the C2 subtype might promote tumor progression by enhancing immune cell infiltration and regulating immune checkpoint expression. Based on differential gene analysis, a risk score model was constructed. It was found that the COL1A1 gene was highly expressed in the high-risk group and was closely associated with immune cell infiltration and immune checkpoint expression.
CONCLUSION: High expression of COL1A1 was significantly correlated with poor prognosis in PCa patients, and its interaction with HAVCR2 may represent a potential therapeutic target. This study provides novel insights into the role of CAF subtypes within the PCa immune microenvironment, highlighting the potential of COL1A1 as both a biomarker and a therapeutic target, which may offer new directions for PCa treatment strategies.
METHODS: This study analyzed transcriptomic data and clinical information from 948 PCa patients sourced from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Three distinct CAF subtypes (C1, C2, C3) were identified, and their roles in tumor progression and the immune microenvironment were explored.
RESULTS: The results demonstrated significant associations between these CAF subtypes and patient prognosis, tumor microenvironment (TME) characteristics, as well as immune cell infiltration. Notably, the C2 subtype exhibited the strongest immune infiltration capacity and highest expression of CAF-related genes, correlating with poor prognosis and marked features of immune evasion. In-depth analysis revealed that the C2 subtype might promote tumor progression by enhancing immune cell infiltration and regulating immune checkpoint expression. Based on differential gene analysis, a risk score model was constructed. It was found that the COL1A1 gene was highly expressed in the high-risk group and was closely associated with immune cell infiltration and immune checkpoint expression.
CONCLUSION: High expression of COL1A1 was significantly correlated with poor prognosis in PCa patients, and its interaction with HAVCR2 may represent a potential therapeutic target. This study provides novel insights into the role of CAF subtypes within the PCa immune microenvironment, highlighting the potential of COL1A1 as both a biomarker and a therapeutic target, which may offer new directions for PCa treatment strategies.