MicroRNAs are Related to Rituximab in Combination with Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Resistance in Patients with Diffuse Large B-cell Lymphoma
Haibo Huang1, Junjiao Gu1, Shuna Yao1, Zhihua Yao1, Yan Zhao1, Qingxin Xia2, Jie Ma2, Ling Mai3, Shujun Yang1, Yanyan Liu1
1 Department of Internal Medicine, Henan Cancer Hospital, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China
2 Department of Pathology, Henan Cancer Hospital, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China
3 Administration Office, Henan Institute of Cancer Research, Zhengzhou, Henan, China
Dr. Yanyan Liu
Department of Internal Medicine, Henan Cancer Hospital, Affiliated Cancer Hospital of Zhengzhou University, 127 Dongming Road, Zhengzhou 450008, Henan
Source of Support: The study was supported by the Natural Science Foundation of China (81071938 and 81470365),, Conflict of Interest: None
Aim: Rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) treatment failure is a rigorous problem in patients with diffuse large B-cell lymphoma (DLBCL), which usually predicts poor survival. The study explored the association of microRNAs with R-CHOP resistance in order to find reliable predictive factors and novel therapeutic targets.
Methods: Forty-five newly diagnosed cases with DLBCL were administered with R-CHOP regimen. Thirty-three of them were divided into the sensitive group and 12 of them into the resistant group based on their response to the treatment. Both microRNAs and gene expression profilings were examined with microarray in these patients.
Results: Six microRNAs were found to have significant difference between R-CHOP sensitive and resistant groups, including microRNA-9, microRNA-146a, microRNA-363, microRNA-488, microRNA-548d-3p, and microRNA-219-1-3p (P < 0.05 and absolute value of ΔΔCt > 1). Multivariate analysis showed that both microRNA-146a and microRNA-548d-3p were inversely correlated with resistance while microRNA-363 and microRNA-219-1-3p were directly correlated with resistance. Although both molecular subtypes based on cellular origin (Pearson correlation = 0.368, P = 0.023) and multiple extranodal involvement (Pearson correlation = 0.352, P = 0.030) manifested the association with R-CHOP resistance, these specific microRNAs remained independent predictors of clinical outcome in multivariate analysis. In addition, microRNA-146a was proved to have linkages with multiple extranodal involvements. Molecular subtypes based on a cellular origin were not verified to correlate with specific microRNAs. These specific microRNAs could predict resistance in 92.1% of patients in the present study.
Conclusion: The expression of specific microRNAs may serve as useful biomarker for prediction of response to R-CHOP therapy in patients with DLBCL.