Overexpression of FABP7 promotes cell growth and predicts poor prognosis of clear cell renal cell carcinoma

Jiancheng Zhou; Zhuo Deng; Yule Chen; Yang Gao; Dapeng Wu; Guodong Zhu; Lei Li; Wenbin Song; Xinyang Wang; Kaijie Wu; Dalin He

doi:10.1016/j.urolonc.2014.08.001

Overexpression of FABP7 promotes cell growth and predicts poor prognosis of clear cell renal cell carcinoma

Urol Oncol. 2015 Mar;33(3):113.e9-17. doi: 10.1016/j.urolonc.2014.08.001. Epub 2014 Sep 2.

Authors

Jiancheng Zhou¹, Zhuo Deng², Yule Chen¹, Yang Gao¹, Dapeng Wu¹, Guodong Zhu¹, Lei Li¹, Wenbin Song¹, Xinyang Wang¹, Kaijie Wu³, Dalin He⁴

Affiliations

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.

PMID: 25192834
DOI: 10.1016/j.urolonc.2014.08.001

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.

Keywords: Cell growth; FABP7; Gene profile; Prognostic factor; Renal cell carcinoma.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Carcinoma, Renal Cell / metabolism*
Carrier Proteins / metabolism*
Cell Cycle
Cell Line, Tumor
Cell Proliferation
Cluster Analysis
Cohort Studies
DNA Methylation
Fatty Acid-Binding Protein 7
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic*
Humans
Immunohistochemistry
Kidney Neoplasms / metabolism*
Male
Middle Aged
Mutation
Neoplasm Recurrence, Local
Prognosis
Retrospective Studies
Tissue Array Analysis
Tumor Suppressor Proteins / metabolism*
Up-Regulation

Substances

Carrier Proteins
FABP7 protein, human
Fatty Acid-Binding Protein 7
Tumor Suppressor Proteins