Liang Hai-Qi, He Qi-Huan, Wei Qiu-Ju, Mo Qi-Zhou, Yang Guang-Lin, Wei Fa-Ye, Wei Li-Wei, Li Yu-Jian, Qin Min, Cheng Ji-Wen
Department of Urology, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, 530021, China.
Guangxi Medical University, Nanning, China.
Genes Genomics. 2025 May;47(5):541-557. doi: 10.1007/s13258-025-01624-z. Epub 2025 Feb 26.
CTHRC1 overexpresses in prostate cancer and is associated with the proliferation, invasion and migration of prostate cancer cells. However, the roles and mechanisms of CTHRC1 expression in prostate cancer prognosis and treatment outcomes remain unknown.
This study aimed to explore the expression and gene function of CTHRC1 in prostate cancer, investigate the prognostic value and potential effect in the treatment of prostate cancer.
Bulk and single-cell RNA sequencing analyses were used to evaluate the expression of CTHRC1 in prostate cancer. All data used in the study were obtained from publicly available sources to ensure transparency. Study enrolled 1999 cases of prostate cancer and 531 normal controls. Single-cell RNA sequencing profile included 62,995 cells from seven prostate primary tumors. CTHRC1 expression and prognosis analyses were conducted with these samples and verified by immunohistochemical staining. CIBERSORT algorithm was used to assess the tumor immune infiltrating cells based on bulk mRNA sequencing profiles. Genomics of drug sensitivity in cancer (GDSC) database was used to predict IC50 to anti-androgen therapy (ADT) drugs of the samples.
CTHRC1 expressed in prostate cancer was higher than that in normal prostate tissue, and the expression increased with the progress of prostate cancer. CTHRC1 was the risk factor of progression-free interval (PFI). CTHRC1 was positively correlated with the infiltration of tumor-associated macrophages (TAMs). Myofibroblast-like cancer-associated fibroblasts (myCAFs) were the major CTHRC1 expressers in prostate cancer. TGF-β signaling activated in CTHRC1-positive myCAFs and was involved in TAMs polarization. Biological functions of myCAFs were enriched in hormone response and metabolism. CTHRC1 may regulate androgen receptor signaling through CCN2/CAV1/AR pathway. Moreover, ADT drug Bicalutamide and AZD3514 were less sensitive in the high CTHRC1 expression tumors.
As a potential molecular target of ADT resistance in prostate cancer, CTHRC1 provides a new promising molecular approach for the diagnosis and treatment of prostate cancer.
CTHRC1在前列腺癌中过表达，与前列腺癌细胞的增殖、侵袭和迁移有关。然而，CTHRC1表达在前列腺癌预后和治疗结果中的作用及机制仍不清楚。
本研究旨在探讨CTHRC1在前列腺癌中的表达及基因功能，研究其对前列腺癌的预后价值及在治疗中的潜在作用。
采用批量和单细胞RNA测序分析来评估CTHRC1在前列腺癌中的表达。研究中使用的所有数据均来自公开可用来源，以确保透明度。研究纳入了1999例前列腺癌病例和531例正常对照。单细胞RNA测序图谱包括来自7个前列腺原发性肿瘤的62995个细胞。对这些样本进行CTHRC1表达和预后分析，并通过免疫组织化学染色进行验证。基于批量mRNA测序图谱，使用CIBERSORT算法评估肿瘤免疫浸润细胞。利用癌症药物敏感性基因组学（GDSC）数据库预测样本对抗雄激素治疗（ADT）药物的IC50。
前列腺癌中CTHRC1的表达高于正常前列腺组织，且随着前列腺癌进展表达增加。CTHRC1是无进展生存期（PFI）的危险因素。CTHRC1与肿瘤相关巨噬细胞（TAM）浸润呈正相关。肌成纤维细胞样癌症相关成纤维细胞（myCAF）是前列腺癌中主要的CTHRC1表达细胞。TGF-β信号在CTHRC1阳性的myCAF中激活，并参与TAM极化。myCAF的生物学功能在激素反应和代谢方面富集。CTHRC1可能通过CCN2/CAV1/AR途径调节雄激素受体信号。此外，ADT药物比卡鲁胺和AZD3514在CTHRC1高表达肿瘤中敏感性较低。
作为前列腺癌ADT耐药的潜在分子靶点，CTHRC1为前列腺癌的诊断和治疗提供了一种新的有前景的分子方法。
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