Prognostic molecular markers in resected extrahepatic biliary tract cancers; a systematic review and meta-analysis of immunohistochemically detected biomarkers

Biomark Med. 2015;9(8):763-75. doi: 10.2217/BMM.15.48. Epub 2015 Jul 30.

Abstract

Better prognostic information for resected extrahepatic cholangiocarcinoma could guide treatment strategies and potentially improve outcome. This study performed a systematic review and meta-analysis to identify prognostic biomarkers for further investigation.

Methods: Relevant literature was identified using Medline, EMBASE and Web of Science. Primary end point was overall survival assessed on univariate analysis. Log hazard ratio and variance were calculated and pooled using a random effects inverse variance approach. Hazard ratio and 95% confidence intervals were calculated.

Results: Thirty-seven studies, including 2371 patients, met the inclusion criteria. Subsequently nine biomarkers predictive of OS were identified (HR, 95% CI): VEGF (2.32, 1.57-3.44), COX-2 (1.94, 1.01-3.71), GLUT-1 (2.09, 1.52-2.89), Cyclin D1 (1.96, 1.02-3.76), p16 (0.68, 0.47-0.98), p27 (0.48, 0.3-0.78), E-Cadherin (0.47, 0.35-0.63), Fascin (2.19, 1.35-3.55), and Ki-67 (1.69, 1.02-2.79).

Conclusion: Meta-analysis has identified a number of prognostic biomarkers for resected extrahepatic cholangiocarcinoma. These markers warrant further investigation as potential therapeutic targets and validation in a prospective setting.

Keywords: COX2; CYCLIN; E-Cadherin; Fascin; GLUT1; Ki67; VEGF; cholangiocarcinoma; p16; p27.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Bile Ducts, Extrahepatic / metabolism*
  • Bile Ducts, Extrahepatic / pathology
  • Biliary Tract Neoplasms / diagnosis
  • Biliary Tract Neoplasms / metabolism*
  • Biomarkers, Tumor / analysis*
  • Humans
  • Immunohistochemistry / methods*
  • Immunohistochemistry / statistics & numerical data
  • Prognosis
  • Proportional Hazards Models
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Survival Analysis

Substances

  • Biomarkers, Tumor