Clinical correlation of B7-H3 and B3GALT4 with the prognosis of colorectal cancer

World J Gastroenterol. 2018 Aug 21;24(31):3538-3546. doi: 10.3748/wjg.v24.i31.3538.

Abstract

Aim: To investigate the expression and clinical significance of B7 homolog 3 (B7-H3) and β-1,3-galactosyltransferase-4 (B3GALT4) in colorectal cancer (CRC) patients.

Methods: Using tissue microarray, we identified the expression of B7-H3 and B3GALT4 in 223 CRC patient samples by immunohistochemistry and evaluated the possible correlation between B7-H3 and B3GALT4 and clinical outcomes. Further, the mRNA and protein expression were identified to establish the regulatory relationship of B7-H3 with B3GALT4 in vitro.

Results: A significant positive correlation between B7-H3 and B3GALT4 was observed in CRC specimens (r = 0.219, P = 0.001). High expression of B7-H3 was identified as a significant independent predictor of poor overall survival (OS) [hazard ratio (HR) = 1.781; 95%CI: 1.027-3.089; P = 0.040]. Moreover, high expression of B3GALT4 was also recognized as an independent predictor of inferior OS (HR = 1.597; 95%CI: 1.007-2.533; P = 0.047). Additionally, CRC patients expressing both high B7-H3 and high B3GALT4 contributed to a significant decrease in OS (HR = 2.283; 95%CI: 1.289-4.042; P = 0.005). In CRC cell lines with stable expression of high B7-H3, the mRNA and protein expressions of B3GALT4 were significantly upregulated. Similarly, the expression of B3GALT4 was significantly reduced when expression of B7-H3 was knocked down.

Conclusion: The expression of B3GALT4 in CRC is positively correlated with B7-H3 expression in vitro. B7-H3/B3GLAT4 may be used as dual prognostic biomarkers for CRC.

Keywords: B7 homolog 3; Colorectal cancer; Correlation; Prognosis; β-1,3-galactosyltransferase-4.

MeSH terms

  • B7 Antigens / genetics
  • B7 Antigens / metabolism*
  • Biomarkers, Tumor / metabolism*
  • Cell Line, Tumor
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology*
  • Colorectal Neoplasms / surgery
  • Female
  • Follow-Up Studies
  • Galactosyltransferases / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Prognosis
  • RNA, Messenger / metabolism
  • Tissue Array Analysis
  • Up-Regulation

Substances

  • B7 Antigens
  • Biomarkers, Tumor
  • CD276 protein, human
  • RNA, Messenger
  • Galactosyltransferases
  • UDP-Gal-betaGlcNAc beta 1,3-galactosyltransferase, human