Serpin B5 is a CEA-interacting biomarker for colorectal cancer

Int J Cancer. 2014 Apr 1;134(7):1595-604. doi: 10.1002/ijc.28494. Epub 2013 Oct 11.

Abstract

Serpin B5 is a candidate tumour suppressor, but its oncogenic activity has also been reported. Its function may be affected by protein interactions. The aim of this study was to assess the relationship between serpin B5 and carcinoembryonic antigen (CEA) expression in colorectal cancer (CRC). We also analysed the clinicopathological significance of serpin B5 expression in patients with CRC. Downregulation of serpin B5 was identified in a CEA-suppressed LoVo cell line using two-dimensional gel electrophoresis (2-DE) and matrix-associated laser desorption ionisation-mass spectrometry (MALDI-MS). The specific interaction and co-localisation of serpin B5 with CEA were confirmed by co-immunoprecipitation and confocal microscopy. Western blot analysis and ELISAs revealed significant positive correlations between levels of serpin B5 and CEA in human colon cancer cell lines and in the blood of patients with CRC. Tissue expression of serpin B5 in 377 patients with CRC was significantly associated with serum CEA, histological grade, stage, lymph node metastasis, lymphatic and perineural invasion, and infiltrative border. Strong expression of serpin B5 was also associated with a reduced DFS (p = 0.001) and OS (p = 0.017). Together, these findings describe a relationship between serpin B5 and CEA expression in CRC. Strong expression of serpin B5 was associated with a worse prognosis in patients with CRC and its expression may correlate with CEA levels in CRC.

Keywords: Serpin B5; carcinoembryonic antigen (CEA); colorectal cancer; maspin; prognostic factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / biosynthesis
  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / genetics
  • Caco-2 Cells
  • Carcinoembryonic Antigen / blood*
  • Carcinoembryonic Antigen / genetics
  • Cell Line, Tumor
  • Colorectal Neoplasms / blood*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology
  • Down-Regulation
  • HCT116 Cells
  • Humans
  • Lymphatic Metastasis
  • Prognosis
  • Serpins / biosynthesis
  • Serpins / blood*
  • Serpins / genetics

Substances

  • Biomarkers, Tumor
  • Carcinoembryonic Antigen
  • SERPIN-B5
  • Serpins