Wang Yu, Sun Zhuolun, Lu Shuo, Zhang Xu, Xiao Chutian, Li Tengcheng, Wu Jieying
Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Department of Gynecology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Front Oncol. 2022 Aug 16;12:834524. doi: 10.3389/fonc.2022.834524. eCollection 2022.
Kidney renal clear cell carcinoma (KIRC) represents one of the most fatal cancers, usually showing malignant progression and a high tumor recurrence rate. The urokinase-type plasminogen activator receptor (PLAUR) plays a critical role in the initiation and progression of several cancers, including KIRC. However, the function and mechanism of PLAUR in patients with KIRC are still unclear and require further investigation. In the present study, we first explored the expression profile and prognostic values of PLAUR in pan-cancer based on The Cancer Genome Atlas and Genotype-Tissue Expression databases. PLAUR was upregulated in multiple cancers and was significantly associated with poor overall survival and disease-free survival only in patients with KIRC. Subsequently, the PVT1/SNHG15-hsa-miR-532-3p axis was identified as the most potential upstream regulatory network of PLAUR in KIRC. In addition, PLAUR expression was closely associated with tumor-infiltrating immune cells, tumor immunity biomarkers, and immunomodulator expression. Furthermore, we constructed a multiple-gene risk prediction signature according to the PLAUR-related immunomodulators (PRIs). A prognostic nomogram was then developed to predict the 1-, 3-, and 5-year survival probabilities of individuals. In conclusion, our study identified the PVT1/SNHG15-hsa-miR-532-3p-PLAUR axis and a prognostic signature of PRIs, which could be a reference for future clinical research.
肾透明细胞癌(KIRC)是最致命的癌症之一,通常表现出恶性进展和高肿瘤复发率。尿激酶型纤溶酶原激活物受体(PLAUR)在包括KIRC在内的几种癌症的发生和发展中起关键作用。然而,PLAUR在KIRC患者中的功能和机制仍不清楚,需要进一步研究。在本研究中,我们首先基于癌症基因组图谱和基因型-组织表达数据库,探索了PLAUR在泛癌中的表达谱和预后价值。PLAUR在多种癌症中上调,仅在KIRC患者中与较差的总生存期和无病生存期显著相关。随后,PVT1/SNHG15-hsa-miR-532-3p轴被确定为KIRC中PLAUR最具潜力的上游调控网络。此外,PLAUR表达与肿瘤浸润免疫细胞、肿瘤免疫生物标志物和免疫调节剂表达密切相关。此外,我们根据PLAUR相关免疫调节剂(PRIs)构建了一个多基因风险预测特征。然后开发了一个预后列线图来预测个体的1年、3年和5年生存概率。总之,我们的研究确定了PVT1/SNHG15-hsa-miR-532-3p-PLAUR轴和PRIs的预后特征,可为未来的临床研究提供参考。