Li Sen, Cheng Yongbiao, Cheng Gong, Xu Tianbo, Ye Yuzhong, Miu Qi, Cao Qi, Yang Xiong, Ruan Hailong, Zhang Xiaoping
Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Institute of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Oncol. 2021 May 18;11:649761. doi: 10.3389/fonc.2021.649761. eCollection 2021.
Renal cell carcinoma (RCC) is the most frequent malignant tumor of the kidney. 30% of patients with RCC are diagnosed at an advanced stage. Clear cell renal cell carcinoma (ccRCC) is the most common pathological subtype of RCC. Currently, advanced ccRCC lacks reliable diagnostic and prognostic markers. We explored the potential of SAA1 as a diagnostic and prognostic marker for advanced ccRCC. In this study, we mined and analyzed the public cancer databases (TCGA, UALCAN and GEPIA) to conclude that SAA1 was up-regulated at mRNA and protein levels in advanced ccRCC. We further found that hypomethylation of SAA1 promoter region was responsible for its high expression in ccRCC. Receiver operating characteristic curve (ROC) indicated that high SAA1 levels could distinguish advanced ccRCC patients from normal subjects (p < 0.0001). Kaplan-Meier curve analysis showed that high SAA1 levels predicted poor overall survival time (p < 0.0001) and poor disease-free survival time (p = 0.0003). Finally, the functional roles of SAA1 were examined using a si-SAA1 knockdown method in RCC cell lines. Our results suggest that SAA1 may possess the potential to serve as a diagnostic and prognostic biomarker for advanced ccRCC patients. Moreover, targeting SAA1 may represent as a novel therapeutic target for advanced ccRCC patients.
肾细胞癌（RCC）是最常见的肾脏恶性肿瘤。30%的RCC患者在晚期被诊断出来。透明细胞肾细胞癌（ccRCC）是RCC最常见的病理亚型。目前，晚期ccRCC缺乏可靠的诊断和预后标志物。我们探讨了血清淀粉样蛋白A1（SAA1）作为晚期ccRCC诊断和预后标志物的潜力。在本研究中，我们挖掘并分析了公共癌症数据库（TCGA、UALCAN和GEPIA），得出SAA1在晚期ccRCC的mRNA和蛋白质水平上均上调的结论。我们进一步发现，SAA1启动子区域的低甲基化是其在ccRCC中高表达的原因。受试者工作特征曲线（ROC）表明，高SAA1水平可区分晚期ccRCC患者与正常受试者（p < 0.0001）。Kaplan-Meier曲线分析表明，高SAA1水平预示着总生存时间较差（p < 0.0001）和无病生存时间较差（p = 0.0003）。最后，我们在RCC细胞系中使用si-SAA1敲低方法检测了SAA1的功能作用。我们的结果表明，SAA1可能具有作为晚期ccRCC患者诊断和预后生物标志物的潜力。此外，靶向SAA1可能代表晚期ccRCC患者的一种新的治疗靶点。
