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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

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 selec...

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Main Authors: Ting, Choo-Yuen, Tan, Soo-Yong, Gan, Gin Gin, Zain, Shamsul Mohd, Pung, Yuh-Fen, Ong, Diana Bee-Lan, Bee, Ping Chong
Format: Article
Published: Wiley 2022
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R Medicine
Online Access:http://eprints.um.edu.my/41419/
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spelling my.um.eprints.414192023-09-22T03:09:26Z http://eprints.um.edu.my/41419/ 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 Ting, Choo-Yuen Tan, Soo-Yong Gan, Gin Gin Zain, Shamsul Mohd Pung, Yuh-Fen Ong, Diana Bee-Lan Bee, Ping Chong R Medicine 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. Wiley 2022-10 Article PeerReviewed 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 <https://doi.org/10.1111/ijlh.13928>. 10.1111/ijlh.13928
institution Universiti Malaya
building UM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaya
content_source UM Research Repository
url_provider http://eprints.um.edu.my/
topic R Medicine
spellingShingle R Medicine
Ting, Choo-Yuen
Tan, Soo-Yong
Gan, Gin Gin
Zain, Shamsul Mohd
Pung, Yuh-Fen
Ong, Diana Bee-Lan
Bee, Ping Chong
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
description 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.
format Article
author Ting, Choo-Yuen
Tan, Soo-Yong
Gan, Gin Gin
Zain, Shamsul Mohd
Pung, Yuh-Fen
Ong, Diana Bee-Lan
Bee, Ping Chong
author_facet Ting, Choo-Yuen
Tan, Soo-Yong
Gan, Gin Gin
Zain, Shamsul Mohd
Pung, Yuh-Fen
Ong, Diana Bee-Lan
Bee, Ping Chong
author_sort Ting, Choo-Yuen
title 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
title_short 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_sort 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
publisher Wiley
publishDate 2022
url http://eprints.um.edu.my/41419/
_version_ 1778161670168772608
score 13.211869

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