Downregulation of hsa‐miR‐548d‐3p and overexpression of HOXA9 in diffuse large B‐cell lymphoma patients and the risk of R‐CHOP chemotherapy resistance and disease progression

Introduction Routine categorization of DLBCL patients into GCB and non‐GCB groups by Hans' criteria could not accurately predict chemotherapy resistance and disease progression in patients treated with standard R‐CHOP therapy. There is a need to identify better biomarker predictors to enhance assisted selection of chemotherapy regimens for DLBCL patients. Aim of the study To identify dysregulated miRNAs and mRNAs that are predictive of resistance to R‐CHOP chemotherapy or disease progression in patients with DLBCL. Methods miRNA and mRNA profiling were performed on archival FFPE samples of the DLBCL patients. miRabel and miRNet bioinformatic tools were applied to determine experimental validated miRNA‐mRNA target interaction. The significance of the genomic predictive values was assessed using adjusted odds ratios (AOR) and 95% confidence intervals (CI). Results 19/36 were R‐CHOP therapy‐resistant whilst 17/36 were R‐CHOP therapy‐sensitive. Ten dysregulated miRNAs and 12 dysregulated mRNAs were identified in therapy‐resistant DLBCL patients. These dysregulated miRNAs and mRNA cause therapy resistance and disease progression in DLBCL patients, most likely via upregulation of the anti‐apoptotic protein bcl2, activation of the JAK/STAT signalling pathway and dysregulation of p53 pathway. Downregulation of hsa‐miR‐548d‐3p and overexpression of HOXA9 mRNA were significantly associated with therapy resistance and disease progression in DLBCL patients [hsa‐miR‐548d‐3p AOR: 0.258, 95%CI: 0.097–0.684, p = 0.006]. Conclusion DLBCL patients with downregulation of hsa‐miR‐548d‐3p and overexpression of HOXA9 mRNA are more likely to experience R‐CHOP therapy resistance and disease progression.