Ting, Choo-Yuen and Tan, Soo-Yong and Gan, Gin Gin and Zain, Shamsul Mohd and Pung, Yuh-Fen and Ong, Diana Bee-Lan and Bee, Ping Chong (2022) 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. International Journal of Laboratory Hematology, 44 (5). pp. 907-917. ISSN 1751-5521, DOI https://doi.org/10.1111/ijlh.13928.
Full text not available from this repository.Abstract
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.
| Item Type: | Article |
|---|---|
| Funders: | Scientific and Humanistic Research Foundation Award, Malaysian Society of Haematology, Scientific and Humanistic Research Foundation |
| Uncontrolled Keywords: | Disease progression; Lymphoma large B-cell diffuse; MicroRNA mRNA expression; R-CHOP chemotherapy; Resistance |
| Subjects: | R Medicine |
| Divisions: | Faculty of Medicine |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 22 Sep 2023 03:09 |
| Last Modified: | 22 Sep 2023 03:09 |
| URI: | http://eprints.um.edu.my/id/eprint/41419 |
Actions (login required)
 |
View Item |
