Melanoma in advanced stages is one of the most aggressive tumors and the deadliest of skin cancers. To date, the histopathological staging focuses on tumor thickness, and clinical staging is a major estimate of the clinical behavior of primary melanoma. Here we report on an observational study with in-depth molecular profiling at the protein level including post-translational modifications (PTMs) on eleven primary tumors from melanoma patients. Global proteomics, phosphoproteomics, and acetylomics were performed on each sample. We observed an up-regulation of key mitochondrial functions, including the mitochondrial translation machinery and the down-regulation of structural proteins involved in cell adhesion, the cytoskeleton organization, and epidermis development, which dictates the progression of the disease. Additionally, the PTM level pathways related to RNA processing and transport, as well as chromatin organization, were dysregulated in relation to the progression of melanoma. Most of the pathways dysregulated in this cohort were enriched in genes differentially expressed at the transcript level when similar groups are compared or metastasis to primary melanomas. At the genome level, we found significant differences in the mutation profiles between metastatic and primary melanomas. Our findings also highlighted sex-related differences in the molecular profiles. Remarkably, primary melanomas in women showed higher levels of antigen processing and presentation, and activation of the immune system response. Our results provide novel insights, relevant for developing personalized precision treatments for melanoma patients.

Objectives The multi-biomarker disease activity (MBDA) score is an objective tool for monitoring disease activity in rheumatoid arthritis (RA). Here we report a systematic review and meta-analysis of the clinical value of the MBDA score in RA. Methods We performed a systematic literature search in five medical databases: MEDLINE (via PubMed), Cochrane Library (CENTRAL), Embase, Scopus, and Web of Science, from inception to 13 October 2021. Original articles reporting on the performance of the MBDA score’s correlation with conventional disease activity measures, or the predictive and the discriminative value of the MBDA score for radiographic progression, therapy response, remission, and relapse were included. Results Our systematic search provided a total of 1190 records. After selection and citation searches, we identified 32 eligible studies. We recorded moderate correlations between MBDA score and conventional DAMs at baseline (COR = 0.45, CI: 0.28–0.59; I2 = 71.0% for DAS28 CRP and COR = 0.55, CI: 0.19–0.78; I2 = 0.0% for DAS28-ESR) and at follow-up (COR = 0.44, CI: 0.28–0.57; I2 = 70.0% for DAS28 CRP), and found that the odds of radiographic progression were significantly higher for patients with a high baseline MBDA score (>44) than for patients with a low baseline MBDA score (<30) (OR = 1.03, CI: 1.02–1.05; I2 = 10.0%). Conclusion MBDA score might be used as an objective disease activity marker. In addition, it is also a reliable prognostic marker of radiographic progression.