Elevated expression of KLK8 predicts poor prognosis in colorectal cancer

Biomed Pharmacother. 2017 Apr:88:595-602. doi: 10.1016/j.biopha.2017.01.112. Epub 2017 Jan 28.

Abstract

KLK8, also known as neuropsin, is one of fifteen members of the human kallikrein-related peptidase (KLK) gene family, which consists of enzymes with serine protease enzymatic activity. Aberrant KLK8 expression has been reported in several malignancies. However, the clinicopathological significance and prognostic value of KLK8 expression in colorectal cancer (CRC) are unknown. Therefore, analysis of public datasets, quantitative real-time PCR and western blot analysis were performed to assess KLK8 expression in CRC at both the mRNA and protein level. KLK8 expression was also assessed by immunohistochemistry in a tissue microarray containing 124 CRC specimens. We observed that KLK8 was overexpressed in CRC tissues and was significantly associated with TNM stage, vascular invasion, differentiation and AJCC stage. Univariate and multivariate Cox analyses confirmed that KLK8 is a significant independent prognostic factor for both DFS and OS. Cell function assays also indicated that KLK8 could facilitate CRC cell proliferation, migration and invasion in vitro. In conclusion, elevated KLK8 expression was correlated with the progression of CRC and is a potential independent prognostic indicator for CRC.

Keywords: Colorectal cancer; KLK8; Prognosis; Tumorigenesis.

MeSH terms

  • Aged
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Kallikreins / genetics*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Invasiveness
  • Prognosis
  • Proportional Hazards Models
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • RNA, Messenger
  • KLK8 protein, human
  • Kallikreins