Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan 430030, China.
Int J Mol Sci. 2023 Sep 2;24(17):13603. doi: 10.3390/ijms241713603.
SUMOylation is an important part of post-translational protein modifications and regulates thousands of proteins in a dynamic manner. The dysregulation of SUMOylation is detected in many cancers. However, the comprehensive role of SUMOylation in prostate cancer (PCa) remains unclear. Using 174 SUMOylation-related genes (SRGs) from the MigDSB database and the transcript data of PCa from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), we constructed a SUMOylation-related risk score and correlated it with prognosis, tumor mutation burden (TMB), tumor microenvironment (TME) infiltration, and response to chemotherapy and immunotherapy. Moreover, we validated two vital SRGs by RT-qPCR, western blotting, and immunohistochemistry. Two vital SRGs (DNMT3B and NUP210) were finally selected. The risk score based on these genes exhibited excellent predictive efficacy in predicting the biochemical recurrence (BCR) of PCa. A nomogram involving the risk score and T stage was established to further explore the clinical value of the risk score. We found the high-score group was correlated with worse prognosis, higher TMB, a more suppressive immune microenvironment, and a better response to Docetaxel but worse to PD-1/CTLA-4 blockade. Meanwhile, we validated the significantly higher expression level of NUP210 in PCa at mRNA and protein levels. This study elucidated the comprehensive role of SUMOylation-related genes in PCa. Importantly, we highlighted the role of an important SRG, NUP210, in PCa, which might be a promising target in PCa treatment. A better understanding of SUMOylation and utilizing the SUMOylation risk score could aid in precision medicine and improve the prognosis of PCa.
SUMOylation 是翻译后蛋白质修饰的重要组成部分，以动态方式调节数千种蛋白质。SUMOylation 的失调在许多癌症中都有检测到。然而，SUMOylation 在前列腺癌 (PCa) 中的综合作用尚不清楚。使用 MigDSB 数据库中的 174 个 SUMOylation 相关基因 (SRG) 和癌症基因组图谱 (TCGA) 和基因表达综合 (GEO) 中的 PCa 转录数据，我们构建了一个 SUMOylation 相关风险评分，并将其与预后、肿瘤突变负担 (TMB)、肿瘤微环境 (TME) 浸润以及对化疗和免疫治疗的反应相关联。此外，我们通过 RT-qPCR、western blot 和免疫组织化学验证了两个重要的 SRG。最终选择了两个重要的 SRG (DNMT3B 和 NUP210)。基于这些基因的风险评分在预测 PCa 的生化复发 (BCR) 方面表现出优异的预测效果。建立了一个包含风险评分和 T 分期的列线图，以进一步探讨风险评分的临床价值。我们发现高分组与预后更差、TMB 更高、免疫抑制微环境更明显以及对多西他赛反应更好但对 PD-1/CTLA-4 阻断反应更差相关。同时，我们在 mRNA 和蛋白质水平验证了 NUP210 在 PCa 中表达水平显著升高。这项研究阐明了 SUMOylation 相关基因在 PCa 中的综合作用。重要的是，我们强调了重要的 SRG NUP210 在 PCa 中的作用，它可能是 PCa 治疗的一个有前途的靶点。更好地理解 SUMOylation 并利用 SUMOylation 风险评分可以帮助实现精准医学并改善 PCa 的预后。
