A gene expression inflammatory signature specifically predicts multiple myeloma evolution and patients survival

Cirino Botta, Maria Teresa Di Martino, Cirino Botta, Domenico Ciliberto, Rossi, Maria Cucè, Pierpaolo Correale, Pierfrancesco Tassone, Pierosandro Tagliaferri

Risultato della ricerca: Articlepeer review

23 Citazioni (Scopus)

Abstract

Multiple myeloma (MM) is closely dependent on cross-talk between malignant plasma cells and cellular components of the inflammatory/immunosuppressive bone marrow milieu, which promotes disease progression, drug resistance, neo-angiogenesis, bone destruction and immune-impairment. We investigated the relevance of inflammatory genes in predicting disease evolution and patient survival. A bioinformatics study by Ingenuity Pathway Analysis on gene expression profiling dataset of monoclonal gammopathy of undetermined significance, smoldering and symptomatic-MM, identified inflammatory and cytokine/chemokine pathways as the most progressively affected during disease evolution. We then selected 20 candidate genes involved in B-cell inflammation and we investigated their role in predicting clinical outcome, through univariate and multivariate analyses (log-rank test, logistic regression and Cox-regression model). We defined an 8-genes signature (IL8, IL10, IL17A, CCL3, CCL5, VEGFA, EBI3 and NOS2) identifying each condition (MGUS/smoldering/symptomatic-MM) with 84% accuracy. Moreover, six genes (IFNG, IL2, LTA, CCL2, VEGFA, CCL3) were found independently correlated with patients' survival. Patients whose MM cells expressed high levels of Th1 cytokines (IFNG/LTA/IL2/CCL2) and low levels of CCL3 and VEGFA, experienced the longest survival. On these six genes, we built a prognostic risk score that was validated in three additional independent datasets. In this study, we provide proof-of-concept that inflammation has a critical role in MM patient progression and survival. The inflammatory-gene prognostic signature validated in different datasets clearly indicates novel opportunities for personalized anti-MM treatment.
Lingua originaleEnglish
pagine (da-a)e511-e511
Numero di pagine8
RivistaBlood Cancer Journal
Volume6
Stato di pubblicazionePublished - 2016

All Science Journal Classification (ASJC) codes

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  • ???subjectarea.asjc.2700.2730???

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