Fatty acid binding protein 7 may be a marker and therapeutic targets in clear cell renal cell carcinoma

Kazuhiro Nagao,Egbert Oosterwijk,Sander Jannink,Mirjam De Weijert,Peter Mulders,Yuji Owada,Frank Smit,Nachi Shinohara,Hideyasu Matsuyama

doi:10.1186/s12885-018-5060-8

Abstract

BackgroundTo identify potential therapeutic target in clear cell renal cell carcinoma (ccRCC), we performed a transcriptome analysis. Our analysis showed that fatty acid binding protein 7 (FABP7) has the highest mean differential overexpression in ccRCC compared to normal kidney. We aimed to investigate the significance of FABP7 in ccRCC.MethodsImmunohistochemical staining for 40 advanced ccRCC cases was performed to investigate correlation between clinicopathological parameters and FABP7. They were composed of 40–83 years old cases with 33 male, 22 cases with pT ≥ 3, 19 cases with M1, and 16 cases with grade 3. The effect of gene knockdown was analysed by a cell viability assay and invasion assay in FABP7-overexpressing cell lines (SKRC7 and SKRC10).ResultsOur immunohistochemical analysis showed that higher FABP7 expression significantly correlated with distant metastasis and poor cancer-specific survival (CSS; both p < 0.05). Functional suppression of FABP7 significantly inhibited SKRC10 cell growth (p < 0.05) and resulted in a significant reduction of the invasive potential (p < 0.01), but did not cause growth inhibition of SKRC7 cells. We found that The Cancer Genome Atlas Research Network (TCGA) database shows FABP6 and 7 as equally overexpressed in the FABP family. Functional suppression of fatty acid binding protein 6 (FABP6) resulted in significant growth inhibition of SKRC7 cells (p < 0.005).ConclusionsFunctional suppression of FABP7 significantly reduced cell viability and invasive potential in a ccRCC cell line. FABP7 may play a role in progression in some metastatic ccRCCs. The suppressed function may be compensated by another FABP family member.

Highlights

To identify potential therapeutic target in clear cell renal cell carcinoma, we performed a transcriptome analysis
Patients’ characteristics in the cases analyzed by fatty acid binding protein 7 (FABP7) immunohistochemical staining We retrospectively reviewed the clinical data of 40 patients with metastatic clear cell renal cell carcinoma (ccRCC) who had undergone nephrectomy, followed by systemic therapy using either a cytokine, vascular endothelial growth factor (VEGF)-TKIs, or mammalian target of rapamycin (mTOR) inhibitors in Yamaguchi University Hospital
Five genes (PHD3, FABP7, carbonic anhydrase IX (CAIX), NDUFA4L2, and monocarboxylate transporter 4 (MCT4)) were expressed approximately 10-fold higher in ccRCC specimens compared to normal kidney samples (Fig. 1a)

Summary

Introduction

To identify potential therapeutic target in clear cell renal cell carcinoma (ccRCC), we performed a transcriptome analysis. Renal cell carcinoma (RCC) accounts for 3% of all cancer cases in adults, and it is the 11th most common cancer in men and the 14th most common in women. Clear cell RCC (ccRCC) is the most prevalent pathological subtype of this cancer, accounting for 80% of all cases. VEGF tyrosine kinase inhibitors (VEGF-TKIs) and mammalian target of rapamycin (mTOR) inhibitors significantly extend the progression free survival of patients with metastatic RCC [4], drug resistance invariably occurs. Cabozantinib, an inhibitor of tyrosine kinases including MET, VEGF receptor, and Anexelekto [5], and nivolumab, an immune check point inhibitor targeting

Objectives

Methods

Results

Conclusion