Low level of PDZ domain containing 1 (PDZK1) predicts poor clinical outcome in patients with clear cell renal cell carcinoma.
Low level of PDZ domain containing 1 (PDZK1) predicts poor clinical outcome in patients with clear cell renal cell carcinoma.
复制标题
低水平的 PDZ 结构域包含 1 (PDZK1) 预示着透明细胞肾细胞癌患者临床结果不佳
DOI：
10.1016/j.ebiom.2016.12.003
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发表时间：
2017-02
期刊：
影响因子：
11.1
通讯作者：
He J
中科院分区：
文献类型：
--
作者：
Zheng J;Wang L;Peng Z;Yang Y;Feng D;He J
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. PDZK1, which was involved in cell proliferation and lipid metabolism pathway, was significantly downregulated in ccRCC. PDZK1 was defined as an independent prognostic factor for OS and DFS in univariate and multivariate cox analyses. Low level of PDZK1 could predict poor clinical outcome in patients with ccRCC. Clinical therapeutic effect varies greatly between individuals of clear cell renal cell carcinoma (ccRCC). Development of prognostic molecular biomarkers can help clinicians identify patients in need of early aggressive management. Differentially expressed proteins between tumor and adjacent normal tissues were analyzed by proteomics. Subsequently, bioinformatics assay was combined to screen for prognostic markers in ccRCC. PDZ domain containing 1 (PDZK1), involved in cell proliferation and lipid metabolism pathway, was significantly downregulated in ccRCC and defined as an independent prognostic factor for poor clinical outcome in ccRCC patients. Our findings will facilitate patient counseling and individualize management of patients with ccRCC.
