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

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.

• Authors: C Botta, M T Di Martino, D Ciliberto, M Cucè, P Correale, M Rossi, P Tagliaferri, P Tassone
• Journal: Blood cancer journal (Blood Cancer J) Vol. 6 Issue 12 Pg. e511 (12 16 2016) ISSN: 2044-5385 [Electronic] United States
• PMID: 27983725 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Neoplasm Proteins

Topics

• Adult
• Aged
• Aged, 80 and over
• Computational Biology
• Disease Progression
• Female
• Gene Expression Regulation, Neoplastic (genetics)
• Humans
• Inflammation (genetics, pathology)
• Male
• Middle Aged
• Multiple Myeloma (genetics, pathology)
• Neoplasm Proteins (biosynthesis, genetics)
• Signal Transduction (genetics)
• Transcriptome (genetics)