Melanoma Prognosis: A REMARK-based systematic review and bioinformatic analysis of immunohistochemical and gene microarray studies
Cet article passe en revue les travaux récents sur des biomarqueurs de pronostic dans le mélanome
Despite intensive research efforts, within-stage survival rates for melanoma vary widely. Pursuit of molecular biomarkers with improved prognostic significance over clinico-histological measures has produced extensive literature. Reviews have synthesized these data but none have systematically partitioned high-quality studies from the remainder across different molecular methods nor examined system properties of that output. Databases were searched for studies analyzing protein expression by immunohistochemistry (IHC) (n=617, extending the only systematic review to date (1) by 102 studies), or gene expression microarray studies (n=45) in melanoma, in relation to outcome. REMARK-derived criteria were applied to identify high-quality studies. Biomarkers and pathways were functionally assessed using gene ontology software. Most manuscripts did not meet REMARK-based criteria, an ongoing trend that likely impedes translational research. Across REMARK-compliant literature, 41 proteins were significantly associated with outcome. Multimarker tests consistently emerged among the most promising potential biomarkers, indicating a need to continue assessing candidates in that composite setting. Twenty-one canonical pathways were populated by outcome-related proteins but not by those that failed to show such an association; we propose this set of pathways warrants closer investigation to understand drivers of poor outcome in melanoma. Two gene expression microarray studies met REMARK-based criteria reflecting a genuine paucity of literature in the area. The 254 outcome-related genes were examined for correspondences with the systematically identified protein "signature". This analysis highlighted PCNA and Survivin as priorities for further examination as biomarkers in melanoma prognosis, and, illustrated ongoing need to integrate alternative approaches to biomarker discovery in melanoma translational research.
Molecular Cancer Therapeutics , résumé, 2011