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Comparative proteomic profiling identifies potential prognostic factors for human clear cell renal cell carcinoma.

ABSTRACT: The identification of markers for disease diagnostic, prognostic, or predictive purposes will have a great effect in improving patient management. Proteomic?based approaches for biomarker discovery are promising strategies used in cancer research. In this study, we performed quantitative proteomic analysis on four patients including clear cell renal cell carcinoma (ccRCC) and paired adjacent non?cancerous renal tissues using label?free quantitative proteomics and liquid chromatography?tandem mass spectrometry (LC?MS/MS) to identify differentially expressed proteins. Among 3,061 identified non?redundant proteins, we found that 210 proteins were differentially expressed (83 overexpressed and 127 underexpressed) in ccRCC tissue when compared with normal kidney tissues. Two most significantly dysregulated proteins (PCK1 and SNRPF) were chosen to be confirmed by western blotting. Pathway analysis of 210 differentially expressed proteins showed that dysregulated proteins are related to many cancer?related biological processes such as oxidative phosphorylation, glycolysis and amino acid synthetic pathways. Online survival analysis indicated the prognostic value of these dysregulated proteins. In conclusion, we identified some potential diagnostic biomarkers for ccRCC and an in?depth understanding of their involved biological pathways may help pave the way to discover new therapeutic strategies for ccRCC.

SUBMITTER: Sun X

PROVIDER: S-EPMC5112614 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Comparative proteomic profiling identifies potential prognostic factors for human clear cell renal cell carcinoma.

Sun Xiang X Zhang Hongwei H Luo Longhua L Zhong Kezhao K Ma Yushui Y Fan Linlin L Fu Da D Wan Lijuan L

Oncology reports 20161011 6

The identification of markers for disease diagnostic, prognostic, or predictive purposes will have a great effect in improving patient management. Proteomic‑based approaches for biomarker discovery are promising strategies used in cancer research. In this study, we performed quantitative proteomic analysis on four patients including clear cell renal cell carcinoma (ccRCC) and paired adjacent non‑cancerous renal tissues using label‑free quantitative proteomics and liquid chromatography‑tandem mas ...[more]

PMID: 27748938

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Project description:Purpose: In this study, we have undertaken the whole proteomic analysis and got a better understanding of biological processes involved in the development and progression of ccRCC. We hope promising biomarkers can be uncovered to facilitate early diagnosis, predict the prognosis and progression, more importantly, to be applied as potential therapeutic targets. Experimental design: Fresh frozen tissue samples were surgically resected from patients with local or locally advanced ccRCC. Trypsin digested proteins were analyzed using TMT-based LC-MS/MS proteomic approach, followed by bioinformatic analysis. A potential prognostic marker FMNL1 was chosen to be validated in TCGA_KIRC datasets (n=525 and 72), further validation sets (n=10 and 10) and expanded validation sets (n=81 and 16). The effects of FMNL1 on proliferation, migration and invasion were determined by colony formation, wound healing, and transwell assays in 786-O and Caki-1 cells in vitro study. Results: A total of 657 differentially expressed proteins were identified and quantified between ccRCC and adjacent normal tissues (p-value<0.05, FC>2 or<1/2), of which 186 proteins were up-regulated and 471 proteins were down-regulated. Bioinformatic analysis showed enriched metabolic biological processes and pathways. Univariate and multivariate analysis defined FMNL1 as an independent negative prognostic marker in the TCGA datasets. High expression of FMNL1 correlated significantly with tumor stage and distant metastasis (P<0.05) both in the TCGA-KIRC datasets and expanded validation sets. Kaplan-Meier survival curve illustrated that the patients with high FMNL1 protein level had shorter OS time in the expanded validation sets (p=0.0273). In vitro experiments presented the functional effects of FMNL1 knockdown on the inhibition of proliferation, migration and invasion in cancer cell lines. Conclusion and clinical relevance: The proteomic results uncovered sophisticated metabolic reprogramming of ccRCC and indicated that the upregulation of rate-limiting enzymes in glycolysis and mitochondrial impairment may be the cause of metabolic reprogramming in ccRCC. Moreover, FMNL1 has been identified as a promising prognostic marker, and knockdown of FMNL1 could inhibit ccRCC cell proliferation, migration and invasion, which might be used as a new effective therapeutic strategy to inhibit the progression of ccRCC.

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Comparative proteomic profiling identifies potential prognostic factors for human clear cell renal cell carcinoma.

Publications

Comparative proteomic profiling identifies potential prognostic factors for human clear cell renal cell carcinoma.

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