The potential role of the NEK6, AURKA, AURKB, and PAK1 genes in adenomatous colorectal polyps and colorectal adenocarcinoma

Tumour Biol. 2016 Mar;37(3):3071-80. doi: 10.1007/s13277-015-4131-6. Epub 2015 Sep 30.

Abstract

Colorectal adenomatous polyp (CRAP) is a major risk factor for the development of sporadic colorectal cancer (CRC). Histone modifications are one of the epigenetic mechanisms that may have key roles in the carcinogenesis of CRC. The objective of the present study is to investigate the alternations in the defined histone modification gene expression profiles in patients with CRAP and CRC. Histone modification enzyme key gene expressions of the CRC, CRAP, and control groups were evaluated and compared using the reverse transcription PCR (RT-PCR) array method. Gene expression analysis was performed in the CRAP group after dividing the patients into subgroups according to the polyp diameter, pathological results, and morphological parameters which are risk factors for developing CRC in patients with CRAP. PAK1, NEK6, AURKA, AURKB, HDAC1, and HDAC7 were significantly more overexpressed in CRC subjects compared to the controls (p < 0.05). PAK1, NEK6, AURKA, AURKB, and HDAC1 were significantly more overexpressed in the CRAP group compared to the controls (p < 0.005). There were no significant differences between the CRAP and CRC groups with regards to PAK1, NEK6, AURKA, or AURKB gene overexpression. PAK1, NEK6, AURKA, and AURKB were significantly in correlation with the polyp diameter as they were more overexpressed in polyps with larger diameters. In conclusion, overexpressions of NEK6, AURKA, AURKB, and PAK1 genes can be used as predictive markers to decide the colonoscopic surveillance intervals after the polypectomy procedure especially in polyps with larger diameters.

Keywords: AURKA; AURKB; Colorectal adenocarcinoma; Colorectal adenomatous polyp; Epigenetic; Histone modification; NEK6; PAK1.

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Adenomatous Polyposis Coli / genetics*
  • Adenomatous Polyposis Coli / pathology
  • Adult
  • Aged
  • Aurora Kinase A / genetics*
  • Aurora Kinase A / physiology
  • Aurora Kinase B / genetics*
  • Aurora Kinase B / physiology
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Female
  • Humans
  • Male
  • Middle Aged
  • NIMA-Related Kinases / genetics
  • NIMA-Related Kinases / physiology
  • p21-Activated Kinases / genetics*
  • p21-Activated Kinases / physiology

Substances

  • Aurora Kinase A
  • Aurora Kinase B
  • NEK6 protein, human
  • NIMA-Related Kinases
  • PAK1 protein, human
  • p21-Activated Kinases