Prognostic Biomarkers in Patients with Resected Cholangiocarcinoma: A Systematic Review and Meta-analysis

Purpose. Biomarkers for patients with resected cholangiocarcinoma (CC) can improve staging and may ultimately result in personalized medicine. Studies evaluating these biomarkers often have shown inconsistent results. We performed a systematic review and meta-analysis to investigate the prognostic value of all immunohistochemistry-based markers that have been evaluated in patients with resected CC. Methods. In July 2013, we searched the two main medical literature databases: MEDLINE and EMBASE. We extracted hazard ratios (HRs) and associated 95 % confidence intervals (CIs) from the identified studies and performed random-effects model meta-analyses on overall survival (OS) in accordance with preferred reporting items for systematic reviews and meta-analyses statement and reporting recommendations for tumor marker prognostic studies (REMARK) guidelines. Results. A total of 73 studies, including 4,126 patients studying 77 individual biomarkers, met the inclusion criteria. Fourteen studies were graded with a low risk of bias. Biomarkers prognostic of OS in pooled analysis included fascin (HR 2.58; 95 % CI 1.19-5.58), EGFR (HR 1.79; 95 % CI 1.14-2.8), MUC1 (HR 2.52; 95 % CI 1.49-4.26), MUC4 (HR 2.45; 95 % CI 1.56-3.86), and p27 (HR 0.29; 95 % CI 0.14-0.6). Other markers showed promising results in single studies, including HSP27, Akt, HDGF, MUC6, p16, p-4EBP1, S100A4, alpha-SMA, Keratin 903, and TROP2. Conclusions. Meta-analysis demonstrated that the biomarkers fascin, EGFR, MUC1, MUC4, and p27 are associated with survival in patients with resected CC. Future studies should validate these, and other promising biomarkers, and adhere to the REMARK guidelines.