Abstract:
Background:Multiple myeloma (MM) is a disease of malignant plasma cells (PC) with poor survival. Disease progression and treatment relapse are attributed to MM cancer stem cells (CSCs) and signaling molecules such as MUC1 and XBP1. The prognostic value of the expression of CSC associated biomarkers, MUC1 and XBP1 in MM, has not been explored previously
Method:In this study, we determined the immunohistochemical expression of CSC markers (ALDH1, CD117 and CD34), MUC1 and XBP1in 128 MM formalin-fixed paraffin-embedded bone marrow archival blocks. The expression of biomarkers was assessed for association with clinicopathological variables and the overall survival of patients. Descriptive & initial univariate survival analyses were performed using Kaplan Meier curves. Univariate and multivariable analyses were performed using simple and multiple Cox regression models. The results are reported as crude & adjusted hazard ratios with 95% confidence intervals.
Results :Expression of ALDH1 and CD117 was found in 51% and 48% of the tumors, respectively. ALDH1 expression was associated with 1.83 years of reduced survival for patients with CD56 negative tumors. MUC1 expression was observed in 62%, whereas XBP1 was expressed in 48% tumors. Combinatorial group analysis of XBP1 and MUC1 stratified patients into two prognostic groups. Cases with tumors negative for expression of MUC1 and XBP1 (XBP1- / MUC1-) were categorized as a good prognostic group with increased survival of 3.42 years compared to cases with tumors expressing both (Worst prognosis, XBP1+/MUC1+). The adjusted hazard ratio showed a four-fold increased risk of mortality associated with the concordant expression of MUC1 and XBP1 in patients who were >65 years of age
Conclusion: Concordant expression of MUC1 and XBP1 in MM defines a subset of patients with adverse outcomes. Of these, patients diagnosed at >65 years of age have a significantly higher risk of death.
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