Jiancheng Zhou1, Zhuo Deng2, Yule Chen1, Yang Gao1, Dapeng Wu1, Guodong Zhu1, Lei Li1, Wenbin Song1, Xinyang Wang1, Kaijie Wu3, Dalin He4. 1. Department of Urology, First Affiliated Hospital of Medical School, Xi׳an Jiaotong University, Xi׳an, China. 2. Department of Gynecology and Obstetrics, First Affiliated Hospital of Medical School, Xi׳an Jiaotong University, Xi׳an, China. 3. Department of Urology, First Affiliated Hospital of Medical School, Xi׳an Jiaotong University, Xi׳an, China. Electronic address: kaijie_wu@163.com. 4. Department of Urology, First Affiliated Hospital of Medical School, Xi׳an Jiaotong University, Xi׳an, China. Electronic address: dalinhe@yahoo.com.
Abstract
OBJECTIVES: Renal cell carcinoma (RCC) is one of the most lethal urologic malignancies; however, the molecular events supporting RCC carcinogenesis remain poorly understood. The aim of the present study was to determine the differential expression of genes between normal kidney and clear cell RCC (ccRCC) samples and investigate the biological function of the most frequently altered gene in RCC cells. MATERIALS AND METHODS: The gene expression profiles of 60 ccRCC and matched normal kidney samples from The Cancer Genome Atlas were analyzed. The altered genes were subjected to functional annotation clustering and integrative pathway analysis. The expression of one of the most frequently altered gene, fatty acid-binding protein (FABP) 7, in ccRCC and matched normal kidney samples was verified by immunohistochemistry and the association between FABP7 level and patient survival was investigated. Furthermore, FABP7 DNA copy number alteration, methylation, and mutation status in ccRCC from The Cancer Genome Atlas were analyzed. Finally, FABP7-overexpressing RCC cells were generated to determine the function of FABP7 in cell growth and the potential mechanisms of action. RESULTS: FABP7 was significantly up-regulated in ccRCC, and the expression of FABP7 positively correlated with advanced clinical stage and poor survival of patients with ccRCC. FABP7 DNA copy number alteration was not frequently detected in ccRCC, and no mutation of FABP7 was found. FABP7 messenger RNA expression inversely correlated with its DNA methylation. Overexpression of FABP7 in RCC cells enhanced cell growth, clonogenicity, cell cycle progression and activated both extracellular-signal-regulated kinases (ERK) and signal transducer and activator of transcription 3 (Stat3) signaling. CONCLUSION: FABP7 is overexpressed in ccRCC and promotes cell growth by the activation of ERK and Stat3 signaling pathways. Evidence from the clinical observations and experimental data suggests that FABP7 is a novel prognostic marker and potential therapeutic target for ccRCC.
OBJECTIVES:Renal cell carcinoma (RCC) is one of the most lethal urologic malignancies; however, the molecular events supporting RCC carcinogenesis remain poorly understood. The aim of the present study was to determine the differential expression of genes between normal kidney and clear cell RCC (ccRCC) samples and investigate the biological function of the most frequently altered gene in RCC cells. MATERIALS AND METHODS: The gene expression profiles of 60 ccRCC and matched normal kidney samples from The Cancer Genome Atlas were analyzed. The altered genes were subjected to functional annotation clustering and integrative pathway analysis. The expression of one of the most frequently altered gene, fatty acid-binding protein (FABP) 7, in ccRCC and matched normal kidney samples was verified by immunohistochemistry and the association between FABP7 level and patient survival was investigated. Furthermore, FABP7 DNA copy number alteration, methylation, and mutation status in ccRCC from The Cancer Genome Atlas were analyzed. Finally, FABP7-overexpressing RCC cells were generated to determine the function of FABP7 in cell growth and the potential mechanisms of action. RESULTS:FABP7 was significantly up-regulated in ccRCC, and the expression of FABP7 positively correlated with advanced clinical stage and poor survival of patients with ccRCC. FABP7 DNA copy number alteration was not frequently detected in ccRCC, and no mutation of FABP7 was found. FABP7 messenger RNA expression inversely correlated with its DNA methylation. Overexpression of FABP7 in RCC cells enhanced cell growth, clonogenicity, cell cycle progression and activated both extracellular-signal-regulated kinases (ERK) and signal transducer and activator of transcription 3 (Stat3) signaling. CONCLUSION:FABP7 is overexpressed in ccRCC and promotes cell growth by the activation of ERK and Stat3 signaling pathways. Evidence from the clinical observations and experimental data suggests that FABP7 is a novel prognostic marker and potential therapeutic target for ccRCC.
Authors: Diana A van der Plaat; Judith M Vonk; Lies Lahousse; Kim de Jong; Alen Faiz; Ivana Nedeljkovic; Najaf Amin; Cleo C van Diemen; Guy G Brusselle; Yohan Bossé; Corry-Anke Brandsma; Ke Hao; Peter D Paré; Cornelia M van Duijn; Dirkje S Postma; H Marike Boezen Journal: BMC Pulm Med Date: 2019-03-07 Impact factor: 3.317