Low level of PDZ domain containing 1 (PDZK1) predicts poor clinical outcome in patients with clear cell renal cell carcinoma
| Autor: | Junqi He, Ying Yang, Duiping Feng, Junfang Zheng, Zhiqiang Peng, Lei Wang |
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| Rok vydání: | 2017 |
| Předmět: |
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 |
| Zdroj: | EBioMedicine EBioMedicine, Vol 15, Iss C, Pp 62-72 (2017) |
| ISSN: | 2352-3964 |
| DOI: | 10.1016/j.ebiom.2016.12.003 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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