Tr-KIT/c-KIT ratio in renal cell carcinoma

Mol Biol Rep. 2019 Oct;46(5):5287-5294. doi: 10.1007/s11033-019-04985-3. Epub 2019 Jul 24.

Abstract

Truncated KIT (tr-KIT) is an alternative variant of c-KIT protein. Previous studies have clearly documented that c-KIT was associated with various oncogenic processes in RCC. However, the biological significance of tr-KIT in RCC development and progression remains unclear. So, it was aimed to investigate the possible association between RCC and tr-KIT which is thought to activate some oncogenic pathways. In this study, Kidney Cancer cDNA Array containing a total of 48 cDNA samples from the normal kidney tissues of 9 healthy subjects and kidney tumor tissues of 10 stage-1, 5 stage-2, 13 stage-3 and 11 stage-4 RCC patients was used for gene expression analysis. Real-Time PCR method was used to measure tr-KIT/c-KIT expression ratios. tr-KIT/c-KIT expression ratio was compared between tumor and normal samples, and statistically correlated with the clinical parameters of RCC patients. tr-KIT/c-KIT expression ratio was approximately 4-times higher in tumor samples than control ones (p = 0.001). Also, tr-KIT/c-KIT expression ratio was approximately two, three and six times higher in Fuhrman nuclear grades 2, 3 and 4 than normal, respectively (p = 0.009). Moreover, clear cell and papillary RCC has a significantly higher level of tr-KIT/c-KIT expression ratio than chromophobe RCC (p = 0.016). In the current study, it was stated for the first time that tr-KIT/c-KIT expression ratio was up-regulated in RCC tissues, and high tr-KIT/c-KIT expression ratio was correlated with more aggressive clinical features and poor patient prognosis. Our results suggest that increased tr-KIT/c-KIT expression ratio might be useful as a prognostic marker for RCC patients.

Keywords: Fuhrman nuclear grade; Renal cell carcinoma; c-KIT; tr-KIT.

MeSH terms

  • Adult
  • Aged
  • Alternative Splicing*
  • Biomarkers, Tumor / genetics
  • Carcinoma, Papillary / genetics
  • Carcinoma, Papillary / pathology*
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / pathology*
  • Case-Control Studies
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / pathology*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Proto-Oncogene Proteins c-kit / genetics*
  • Up-Regulation*

Substances

  • Biomarkers, Tumor
  • KIT protein, human
  • Proto-Oncogene Proteins c-kit