The role of TRIM51 as a multipurpose biomarker in melanoma

Abstract

BackgroundIdentification of molecular biomarkers through comprehensive multiomics analyses is essential for the implementation of precision medicine.MethodsTo evaluate the association of each gene with sensitivity or resistance to multiple drugs, we adopted a quantitative metric, the drug response score (DRS), and examined the pharmacotranscriptomic characteristics of genes. We performed comprehensive integrative analyses of multiple independent datasets [Cancer Therapeutics Response Portal (CTRP), Profiling Relative Inhibition Simultaneously in Mixtures (PRISM), Gene Expression Omnibus (GEO), and The Cancer Genome Atlas (TCGA)] in the process of screening, proof, and validation of our findings.ResultsThrough a comprehensive pharmacotranscriptomics approach, we found that TRIM51-high cancer cell lines (CCLs) are highly sensitive to multiple BRAF-MEK inhibitors. The association was preserved even when the analysis was restricted to BRAF-mutant melanoma CCLs, indicating the potential of TRIM51 as a BRAF mutation-independent predictive biomarker. Moreover, the expression level of TRIM51 faithfully represented the degree of post-treatment activity and resistance upon treatment with BRAF-MEK inhibitors both in vitro and in clinical situations, suggesting its application as a surrogate marker for the pharmacological activity of BRAF-MEK inhibitors. In addition, the high expression levels of TRIM51 were significantly associated with worse prognosis and immuno-resistance features in melanoma, indicating its role as a prognostic marker.ConclusionsOur findings revealed a novel role for TRIM51 as a multiuse biomarker in melanoma. The strategy of this study will motivate the development of novel clinical markers.