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

BMC Cancer. 2018 Nov 15;18(1):1114. doi: 10.1186/s12885-018-5060-8.

Abstract

Background: To 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.

Methods: Immunohistochemical 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).

Results: Our 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).

Conclusions: Functional 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.

Keywords: Clear cell renal cell carcinoma; Fatty acid binding protein 6; Fatty acid binding protein 7; Prognostic marker; Therapeutic target.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / antagonists & inhibitors
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Renal Cell / drug therapy
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / mortality
  • Carcinoma, Renal Cell / pathology*
  • Cell Line, Tumor
  • Cell Survival
  • Disease Progression
  • Fatty Acid-Binding Protein 7 / antagonists & inhibitors
  • Fatty Acid-Binding Protein 7 / genetics
  • Fatty Acid-Binding Protein 7 / metabolism*
  • Fatty Acid-Binding Proteins / genetics
  • Fatty Acid-Binding Proteins / metabolism*
  • Female
  • Gastrointestinal Hormones / genetics
  • Gastrointestinal Hormones / metabolism*
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques / methods
  • Humans
  • Kidney / pathology
  • Kidney Neoplasms / drug therapy
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / mortality
  • Kidney Neoplasms / pathology*
  • Male
  • Middle Aged
  • Molecular Targeted Therapy / methods
  • Neoplasm Invasiveness / pathology
  • Progression-Free Survival
  • RNA, Small Interfering / metabolism
  • Survival Rate
  • Tumor Suppressor Proteins / antagonists & inhibitors
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • FABP7 protein, human
  • Fatty Acid-Binding Protein 7
  • Fatty Acid-Binding Proteins
  • Gastrointestinal Hormones
  • RNA, Small Interfering
  • Tumor Suppressor Proteins
  • fatty acid-binding protein 6