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Meta-Analysis
. 2015 Jun 30;113(1):107-18.
doi: 10.1038/bjc.2015.179. Epub 2015 Jun 25.

Systematic review and meta-analysis of immunohistochemical prognostic biomarkers in resected oesophageal adenocarcinoma

L H McCormick Matthews  1 , F Noble  2 , J Tod  1 , E Jaynes  3 , S Harris  4 , J N Primrose  2 , C Ottensmeier  5 , G J Thomas  6 , T J Underwood  2
Affiliations
Meta-Analysis

Systematic review and meta-analysis of immunohistochemical prognostic biomarkers in resected oesophageal adenocarcinoma

L H McCormick Matthews et al. Br J Cancer. .

Erratum in

Abstract

Background: Oesophageal adenocarcinoma (OAC) is one of the fastest rising malignancies with continued poor prognosis. Many studies have proposed novel biomarkers but, to date, no immunohistochemical markers of survival after oesophageal resection have entered clinical practice. Here, we systematically review and meta-analyse the published literature, to identify potential biomarkers.

Methods: Relevant articles were identified via Ovid medline 1946-2013. For inclusion, studies had to conform to REporting recommendations for tumor MARKer (REMARK) prognostic study criteria. The primary end-point was a pooled hazard ratio (HR) and variance, summarising the effect of marker expression on prognosis.

Results: A total of 3059 articles were identified. After exclusion of irrelevant titles and abstracts, 214 articles were reviewed in full. Nine molecules had been examined in more than one study (CD3, CD8, COX-2, EGFR, HER2, Ki67, LgR5, p53 and VEGF) and were meta-analysed. Markers with largest survival effects were COX-2 (HR=2.47, confidence interval (CI)=1.15-3.79), CD3 (HR=0.51, 95% CI=0.32-0.70), CD8 (HR=0.55, CI=0.31-0.80) and EGFR (HR=1.65, 95% CI=1.14-2.16).

Discussion: Current methods have not delivered clinically useful molecular prognostic biomarkers in OAC. We have highlighted the paucity of good-quality robust studies in this field. A genome-to-protein approach would be better suited for the development and subsequent validation of biomarkers. Large collaborative projects with standardised methodology will be required to generate clinically useful biomarkers.

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Figures

Figure 1
Figure 1
PRISMA flow chart illustrating stages of selection of final articles for meta-analysis.
Figure 2
Figure 2
Funnel plot showing publication bias for the 58 included studies providing HR and CI. Plotted points are frequently seen away from the ‘0'.
Figure 3
Figure 3
Statistically significant prognostic biomarkers from at least one study in resected oesophageal adenocarcinoma covering all hallmarks of cancer.
Figure 4
Figure 4
Forest plots with associated hazard ratio (HR) and 95% confidence interval. Weights calculated using a random effects model. HR>1 implies worse survival with overexpression, HR<1; improved survival (vertical black line indicates HR of 1; red vertical dotted line indicates overall HR). A full colour version of this figure is available at the British Journal of Cancer journal online.
See this image and copyright information in PMC

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