Introduction: Multiple myeloma (MM) is a common hematologic malignancy accounting for 1% of all cancers and 10% of hematologic malignancies. Despite considerable research efforts, the molecular features that determine response of MM patients to treatment remain unclear. The aim of this study is the discovery of protein biomarkers with high prognostic/predictive value to be further used in a flow cytometry panel and the identification of the molecular mechanisms that can predict responsiveness to commonly used therapeutic regimens for MM.
Methods: MM patients of all stages were included in this study and were grouped in 22 Deep-Responders (DR) and 25 Non-Responders (NR) after treatment with either bortezomib- or lenalidomide/thalidomide-based regimens. CD138+ cells, isolated from these patients prior to any MM-related treatment, were analyzed with Liquid Chromatography coupled to tandem mass spectrometry.
Results: Statistical analysis of the results and shortlisting of the differentially expressed proteins between DR and NR were performed based on compatibility with flow cytometry and resulted in 10 proteins (PCBP2, HNRNPK, MIF, DIABLO, ANXA2, HMGB1, PTBP1, LPAR3, ICAM1, CD48). Moreover, pathway enrichment analysis showed that differentially expressed features from our proteomics and published transcriptomics data aggregate into common molecular pathways. These involve apoptosis, metabolism, signaling and, more importantly, immune response, translation and protein synthesis regulation that are in agreement with the literature and can explain the differences in the response of MM patients to treatment.
Conclusions: Collectively, our results indicate 10 putative biomarkers of responsiveness to commonly used therapeutic regimens for MM, to be further evaluated for their predictive value in flow cytometry, and highlight immune response and protein synthesis as the most crucial biological processes defining response to treatment.
