Zheng Junfang, Wang Lei, Peng Zhiqiang, Yang Ying, Feng Duiping, He Junqi
Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory for Tumor Invasion and Metastasis, Beijing International Cooperation Base for Science and Technology on China-UK Cancer Research, Beijing 100069, China.
Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
EBioMedicine. 2017 Feb;15:62-72. doi: 10.1016/j.ebiom.2016.12.003. Epub 2016 Dec 9.
Clear cell renal cell carcinoma (ccRCC) is the most lethal neoplasm of the urologic system. Clinical therapeutic effect varies greatly between individual ccRCC patients, so there is an urgent need to develop prognostic molecular biomarkers to help clinicians identify patients in need of early aggressive management. In this study, samples from primary ccRCC tumor and their corresponding nontumor adjacent tissues (n=18) were analyzed by quantitative proteomic assay. Proteins downregulated in tumors were studied by GO and KEGG pathways enrichment analyses. Six proteins were found both downregulated and annotated with cell proliferation in ccRCC patients. Of these proteins, PDZK1 and FABP1 were also involved in the lipid metabolism pathway. The downregulation of PDZK1 was further validated in TCGA_KIRC dataset (n=532) and independent set (n=202). PDZK1 could discriminate recurrence, metastasis and prognosis between ccRCC patients. Low level of PDZK1 in both mRNA and protein was associated with reduced overall survival (OS) and disease-free survival (DFS) in two independent sets. In univariate and multivariate analyses, PDZK1 was defined as an independent prognostic factor for both OS and DFS. These findings indicated that low level of PDZK1 could predict poor clinical outcome in patients with ccRCC.
透明细胞肾细胞癌（ccRCC）是泌尿系统中最致命的肿瘤。ccRCC患者个体之间的临床治疗效果差异很大，因此迫切需要开发预后分子生物标志物，以帮助临床医生识别需要早期积极治疗的患者。在本研究中，通过定量蛋白质组学分析对18例原发性ccRCC肿瘤及其相应的非肿瘤相邻组织样本进行了分析。通过GO和KEGG通路富集分析研究肿瘤中下调的蛋白质。在ccRCC患者中发现有6种蛋白质下调且与细胞增殖相关。在这些蛋白质中，PDZK1和FABP1也参与脂质代谢途径。PDZK1的下调在TCGA_KIRC数据集（n = 532）和独立数据集（n = 202）中得到进一步验证。PDZK1可以区分ccRCC患者的复发、转移和预后。在两个独立数据集中，mRNA和蛋白质水平低的PDZK1均与总生存期（OS）和无病生存期（DFS）降低相关。在单变量和多变量分析中，PDZK1被定义为OS和DFS的独立预后因素。这些发现表明，低水平的PDZK1可预测ccRCC患者的不良临床结局。
