Qing Yunhao, Wang Yu, Hu Cheng, Zhang Huimin, Huang Ye'an, Zhang Zixiao, Ma Tan, Zhang Shuoqi, Li Ke
Department of Urology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Transl Androl Urol. 2022 May;11(5):627-642. doi: 10.21037/tau-22-281.
Abnormal regulation of the signaling pathway in prostate cancer (PCa) can promote tumorigenesis, progression, and T cell exhaustion. However, there has not been a comprehensive analysis of family genes (s) as potential therapeutic targets and prognostic biomarkers for PCa patients.
s expressions in various types of cancer tissues and normal adjacent tissues in the TIMER and UALCAN database were screened. Immunohistochemistry (IHC) and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) were applied to validate the expression pattern of s in clinical samples. The relationships of s expression and clinicopathologic parameters or disease-free survival (DFS) were evaluated via GEPIA2 and UALCAN. A proteins network was built using STRING and GeneMANIA. Additionally, s mutation status was analyzed by cBioportal. Finally, we used GDSC and TIMER to investigate signaling-related drugs and immune cell infiltration.
The transcriptional levels of and in PCa tissues were significantly lower than in normal tissues, which was further validated in clinical patients' tissue samples. Furthermore, , , and expressions in PCa were associated with worse DFS. Interestingly, there was a significant positive correlation between s and androgen receptor (), but not with -related genes ( and ). Finally, we found that s expressions were remarkably associated with infiltration of B cells, CD8/CD4 T cells, macrophages, neutrophils, and dendritic cells, which indicated that s mutation status might be a potential therapeutic target for -tinib antineoplastic drugs.
The expression and mutation of in PCa were associated with disease progression, prognosis, immune cell infiltration, and drug sensitivity.
前列腺癌（PCa）中信号通路的异常调节可促进肿瘤发生、进展和T细胞耗竭。然而，尚未对作为PCa患者潜在治疗靶点和预后生物标志物的家族基因进行全面分析。
筛选TIMER和UALCAN数据库中各种类型癌组织及癌旁正常组织中的表达情况。应用免疫组织化学（IHC）和实时定量逆转录聚合酶链反应（qRT-PCR）验证临床样本中的表达模式。通过GEPIA2和UALCAN评估表达与临床病理参数或无病生存期（DFS）的关系。使用STRING和GeneMANIA构建蛋白质网络。此外，通过cBioportal分析突变状态。最后，我们使用GDSC和TIMER研究与信号相关的药物和免疫细胞浸润。
PCa组织中的转录水平显著低于正常组织，这在临床患者的组织样本中得到进一步验证。此外，PCa中的、和表达与较差的DFS相关。有趣的是，与雄激素受体（）之间存在显著正相关，但与相关基因（和）无关。最后，我们发现表达与B细胞、CD8/CD4 T细胞、巨噬细胞、中性粒细胞和树突状细胞的浸润显著相关，这表明突变状态可能是替尼类抗肿瘤药物的潜在治疗靶点。
PCa中的表达和突变与疾病进展、预后、免疫细胞浸润和药物敏感性相关。
