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. 2020 Oct 10;5(4):185-190.
doi: 10.1016/j.ncrna.2020.10.001. eCollection 2020 Dec.

miRNA signature associated with R-CHOP refractoriness in patients diagnosed with diffuse large B cell lymphoma

Oscar Raul Fajardo-Ramirez  1 , Luis Villela  2   3 , Jocelyn Nikita Campa-Carranza  1 , Antonio Ali Perez-Maya  4 , Gissela Borrego-Soto  5 , Martin Ivan Wah-Suarez  6 , Iram Pablo Rodríguez-Sánchez  7 , Patricio A Zapata-Morin  7 , Rocio Ortiz-Lopez  1 , Victor Manuel Treviño  1 , Mariano Garcia-Magariño  1 , Ivan Alberto Marino-Martinez  4   8
Affiliations

miRNA signature associated with R-CHOP refractoriness in patients diagnosed with diffuse large B cell lymphoma

Oscar Raul Fajardo-Ramirez et al. Noncoding RNA Res. .

Abstract

Refractoriness remains as one of the challenges in patients with lymphoma under chemotherapy, and among biological regulators in cells driving this type of response are microRNAs (miRNAs). Different genes are constantly turned on or off according to the miRNAs expression profiles affecting the drug response in patients and their stability in serum and plasma makes them potential prognostic biomarkers in several diseases. Here we described a profile of miRNAs in plasma of diffuse large B cell lymphoma (DLBCL) patients. miRNA expression arrays were carried using pre-treatment plasma samples of sixteen patients, followed by a comparison between the responder and the non-responders. After six cycles of R-CHOP treatment, twelve out of sixteen patients were clinically diagnosed with complete response while in four patients no clinical response was observed. Between these groups, a signature of fifteen differential expressed miRNAs was found. The circulating miRNAs in plasma of patients with no response were related to the drug resistance in other types of cancer, by targeting genes involved in cell proliferation and apoptosis, among other cell processes.

Keywords: Chemoresistance; Diffuse large B cell Lymphoma; Drug response; Gene expression; miRNA.

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Conflict of interest statement

The authors do not have any current potential personal, political or financial interest in the material, information, or techniques described in this paper.

Figures

Fig. 1
Fig. 1
Heat map. showing the miRNAs relative expression and the clustering based on the clinical outcome after treatment.
Fig. 2
Fig. 2
miRNA-target networks. (A) An interaction map between the upregulated miRNAs (red circles) and their target genes (green circles) was created after eliminating genes targeted by three or less miRNAs. Size of the green circles is related to the number of miRNAs targeting the genes (4, 5 or 6 miRNAs). (B) Same map was created for downregulated miRNAs (blue circles), but only genes targeted by three miRNAs were used since no target genes were share for 4 or more RNAs.
Fig. 3
Fig. 3
Predicted biological functions to be the most impacted by the dysregulated miRNAs included in the signature. (A, B) The impact of the 9 upregulated miRNAs on the KEGG and Gene Ontology (GO) biological pathways, respectively, predicted with DIANA microT-CDS tool. (C, D) The impact of the 6 downregulated miRNAs on the KEGG and Gene Ontology (GO) biological pathways, respectively, predicted with DIANA microT-CDS tool. Heatmap representation of the pathways and the significance (determined from log (p-values)) with each miRNA with red indicating the highest level of significance and yellow the lowest level of significance.
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