Low level of PDZ domain containing 1 (PDZK1) predicts poor clinical outcome in patients with clear cell renal cell carcinoma
| العنوان: | Low level of PDZ domain containing 1 (PDZK1) predicts poor clinical outcome in patients with clear cell renal cell carcinoma |
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| المؤلفون: | Junqi He, Ying Yang, Duiping Feng, Junfang Zheng, Zhiqiang Peng, Lei Wang |
| المصدر: | EBioMedicine EBioMedicine, Vol 15, Iss C, Pp 62-72 (2017) |
| بيانات النشر: | Elsevier BV, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Male, Proteomics, 0301 basic medicine, Oncology, CAP70, cystic fibrosis transmembrane conductance regulator associated protein of 70 kDa, Proteome, NHERF, Na+/H+ exchanger regulatory factor, Cell, Gene Expression, lcsh:Medicine, PDZ Domains, Bioinformatics, Metastasis, AUC, area under the curve, Prognostic markers, 0302 clinical medicine, STRING, The Search Tool for the Retrieval of Interacting Genes/Proteins, iTRAQ, isobaric tags for relative and absolute quantitaion, DAVID, The Database for Annotation, Visualization, and Integrated Discovery, BIRC5, baculoviral IAP repeat containing 5, TNM, The tumor-node-metastasis, Aged, 80 and over, lcsh:R5-920, NCCN, national comprehensive cancer network, education.field_of_study, Tissue microarray, General Medicine, Middle Aged, DFS, disease–free survival, FSCN2, fascin actin-bundling protein 2, Prognosis, Kidney Neoplasms, ES, Enrichment Score, Renal cancer, medicine.anatomical_structure, DEPs, differentially expressed proteins, 030220 oncology & carcinogenesis, AJCC, American Joint Committee on Cancer, Immunohistochemistry, Female, lcsh:Medicine (General), GSEA, The gene set enrichment analysis, IHC, immunohistochemistry, Research Paper, Adult, medicine.medical_specialty, FDR, false discovery rate, WB, Western Blotting, Lactate dehydrogenase A, Down-Regulation, ROC, Receiver operator characteristic, Biology, Fatty Acid-Binding Proteins, KEGG, Kyoto Encyclopedia of Genes and Genomes, SR-BI, scavenger receptor class B type I, General Biochemistry, Genetics and Molecular Biology, OS, overall survival, 03 medical and health sciences, NHERF3, Internal medicine, Biomarkers, Tumor, TMA, tissue microarray, medicine, Carcinoma, Humans, KM, Kaplan–Meier, LDHA, lactate dehydrogenase A, PDZ, KEGG, education, UPLC, the Ultra Performance Liquid Chromatography, Carcinoma, Renal Cell, Aged, Cell Proliferation, Neoplasm Staging, GO, gene ontology, CAP70, FABP1, fatty acid binding protein 1, lcsh:R, Computational Biology, Membrane Proteins, Lipid Metabolism, medicine.disease, Clear cell renal cell carcinoma, 030104 developmental biology, CLAMP, ccRCC, clear cell renal cell carcinoma, CA9, carbonic anhydrase IX, Commentary, PDZK1, PDZ domain containing 1, IMP3, insulin-like growth factor mRNA binding protein 3, Neoplasm Grading, Carrier Proteins, TCGA_KIRC, The Cancer Genome Atlas kidney renal clear cell carcinoma |
| الوصف: | 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. Highlights • 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. |
| تدمد: | 2352-3964 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ba8f64b5502a35e2b61a2a5b14ba4d22Test https://doi.org/10.1016/j.ebiom.2016.12.003Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ba8f64b5502a35e2b61a2a5b14ba4d22 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23523964 |
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