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miRNA signature associated with R-CHOP refractoriness in patients diagnosed with diffuse large B cell lymphoma
Oscar Raul Fajardo-Ramirez1, Luis Villela2,3, Jocelyn Nikita Campa-Carranza1
1Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud de la Salud, Mexico.
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.
Insights
Chemotherapy resistance in diffuse large B cell lymphoma (DLBCL) patients may be predicted by specific microRNAs (miRNAs) found in plasma. These circulating miRNAs could serve as biomarkers for treatment response.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Chemotherapy resistance is a significant challenge in treating diffuse large B cell lymphoma (DLBCL).
- MicroRNAs (miRNAs) are key regulators of gene expression and are implicated in drug resistance.
- The stability of miRNAs in biological fluids suggests their potential as prognostic biomarkers.
Purpose of the Study:
- To identify a plasma microRNA (miRNA) expression profile in diffuse large B cell lymphoma (DLBCL) patients.
- To compare miRNA profiles between patients who respond and do not respond to R-CHOP chemotherapy.
- To explore the potential of circulating miRNAs as biomarkers for predicting treatment outcomes in DLBCL.
Main Methods:
- Plasma samples were collected from sixteen DLBCL patients before treatment.
- miRNA expression arrays were used to analyze miRNA profiles.
- Expression levels were compared between patients achieving complete response and those showing no response after six cycles of R-CHOP.
Main Results:
- A distinct signature of fifteen differentially expressed miRNAs was identified between responders and non-responders.
- The identified miRNAs in non-responders were linked to drug resistance mechanisms in other cancers.
- These miRNAs target genes involved in critical cellular processes such as proliferation and apoptosis.
Conclusions:
- Plasma miRNA profiles can differentiate between responders and non-responders to R-CHOP chemotherapy in DLBCL.
- Circulating miRNAs may serve as predictive biomarkers for chemotherapy response in DLBCL.
- The identified miRNA signature offers insights into the molecular mechanisms of drug resistance in DLBCL.
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