title: Low level of PDZ domain containing 1 (PDZK1) predicts poor clinical outcome in patients with clear cell renal cell carcinoma.
abstract: 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.
authors.affiliation: 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.
authors.forename: Junfang
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Peng
authors.affiliation: Core Facilities Center, Capital Medical University, Beijing 100069, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Radiology, First Hospital of Shanxi Medical University, Taiyuan 030001, China.
authors.forename: Duiping
authors.initials: D
authors.lastname: Feng
authors.affiliation: 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. Electronic address: jq_he@ccmu.edu.cn.
authors.forename: Junqi
authors.initials: J
authors.lastname: He
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics*; D049109:Cell Proliferation; D019295:Computational Biology / Q000379:methods; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D050356:Lipid Metabolism; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D020543:Proteome; D040901:Proteomics / Q000379:methods
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; C493319:FABP1 protein, human; D050556:Fatty Acid-Binding Proteins; D008565:Membrane Proteins; C484659:PDZK1 protein, human; D020543:Proteome
keywords: CAP70; CLAMP; NHERF3; PDZ; Prognostic markers; Proteomics; Renal cancer