A 5-Gene Stemness Score for Rapid Determination of Risk in Multiple Myeloma

Risk stratification in patients with multiple myeloma (MM) remains a challenge. As clinicopathological characteristics have been demonstrated insufficient for exactly defining MM risk, and molecular biomarkers have become the focuses of interests. Prognostic predictions based on gene expression profiles (GEPs) have been the most accurate to this day. The purpose of our study was to construct a risk score based on stemness genes to evaluate the prognosis in MM.

Bioinformatics studies by ingenuity pathway analyses in side population (SP) and non-SP (MP) cells of MM patients were performed. Firstly, co-expression network was built to confirm hub genes associated with the top five Kyoto Encyclopedia of Genes and Genomes pathways. Functional analyses of hub genes were used to confirm the biologic functions. Next, these selective genes were utilized for construction of prognostic model, and this model was validated in independent testing sets. Finally, five stemness genes (ROCK1, GSK3B, BRAF, MAPK1 and MAPK14) were used to build a MM side population 5 (MMSP5) gene model, which was demonstrated to be forcefully prognostic compared to usual clinical prognostic parameters by multivariate cox analysis. MM patients in MMSP5 low-risk group were significantly related to better prognosis than those in high-risk group in independent testing sets.

Our study provided proof-of-concept that MMSP5 model can be adopted to evaluate recurrence risk and clinical outcome for MM. The MMSP5 model evaluated in different databases clearly indicated novel risk stratification for personalized anti-MM treatments.