Kadeerhan Gaohaer, Xue Bo, Wu Xiaolin, Hu Xiaofeng, Tian Jun, Wang Dongwen
National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Shenzhen 518116, China.
Shanxi Medical University Shanxi 030012, China.
Am J Cancer Res. 2023 Jul 15;13(7):2861-2877. eCollection 2023.
Biochemical recurrence (BCR) is considered as an early sign of prostate cancer (PCa) progression after initial treatment, such as radical prostatectomy and radiotherapy; hence, it is important to stratify patients at risk of BCR. In this study, we established a robust 8-gene signature (APOF, Clorf64, RPE65, SEMG1, ARHGDIG, COMP, MKI67 and PRAME) based on the PCa transcriptome profiles in the Cancer Genome Atlas (TCGA) for predicting BCR-free survival of PCa, which was further validated in the MSK-IMPACT Clinical Sequencing Cohort (MSKCC) PCa cohort. Moreover, we found that one risk-related gene (PRAME) was upregulated in tumor samples, particularly in high-risk group was well as in patients metastatic tumor and was correlated with chemotherapeutic drug response. In vitro experiments showed that knocking down PRAME reduced the proliferation, migration, and invasion of PCa cells. Therefore, our study established a new 8-gene signature that could accurately predict the BCR risk of PCa. Inhibition of PRAME attenuated the proliferation, invasion, and migration of PCa cells. These findings provide a novel tool for stratifying high-risk PCa patient and shed light on the mechanism of PCa progression.
生化复发（BCR）被认为是前列腺癌（PCa）初始治疗（如根治性前列腺切除术和放射治疗）后疾病进展的早期迹象；因此，对有BCR风险的患者进行分层很重要。在本研究中，我们基于癌症基因组图谱（TCGA）中的PCa转录组谱建立了一个强大的8基因特征（APOF、Corf64、RPE65、SEMG1、ARHGDIG、COMP、MKI67和PRAME），用于预测PCa的无BCR生存期，并在MSK-IMPACT临床测序队列（MSKCC）的PCa队列中进一步验证。此外，我们发现一个风险相关基因（PRAME）在肿瘤样本中上调，特别是在高危组以及转移性肿瘤患者中，并且与化疗药物反应相关。体外实验表明，敲低PRAME可降低PCa细胞的增殖、迁移和侵袭能力。因此，我们的研究建立了一种新的8基因特征，可准确预测PCa的BCR风险。抑制PRAME可减弱PCa细胞的增殖、侵袭和迁移能力。这些发现为高危PCa患者分层提供了一种新工具，并阐明了PCa进展的机制。
