Circulating microRNA-125b and microRNA-130a expression profiles predict chemoresistance to R-CHOP in diffuse large B-cell lymphoma patients

Abstract

Abstract. Numerous studies have reported the aberrant expression profiles of microRNAs (miRNAs) in diffuse large B-cell lymphoma (DLBCL), although very few of these studies were concerned with chemoresistance to R-CHOP in DLBCL patients. This study was designed to assess the correlation between circulating miRNA expression and chemoresistance and prognosis in DLBCL patients. At the start of the study, we demonstrated that miRNA expression levels in serum were significantly associated with those in formalin-fixed, paraffin-embedded tissues, which indicated that circulating miRNAs may be powerful, non-invasive biomarkers reflecting miRNAs levels isolated from tumor tissue. Then from eight potential drug-resistant miRNAs which were deregulated in DLBCL and which had been reported to be associated with drug resistance in other carcinomas, we screened out the circulating miR-125b and miR-130a, which may related to R-CHOP resistance. Dynamic monitoring of the levels of circulating miR-125b and miR-130a further demonstrated that they were involved in recurrence, progression and chemoresistance in DLBCL patients. Finally, we demonstrated that high miR-125b indicated poor prognosis, as patients with higher miR-125b levels had a shorter overall survival. To our knowledge, this is the first study demonstrating that miR-125b and miR-130a are associated with the risk of chemoresistance in DLBCL patients, and that dynamic monitoring of the levels of circulating miR-125b and miR-130a predicts the therapeutic response and disease status of DLBCL patients.

A Circulating microRNA Signature Predicts Age-Based Development of Lymphoma

“…In addition to miR-27a and let-7b, the following miRNAs from the miRNA signature were considered to be tumor suppressors for DLBCL: miR-15a [29, 32, 43, 44], let-7c [20, 23], miR-24 [12], and miR-497 [9, 45]. The following miRNAs were categorized as oncomiRs for DLBCL: miR-10b [44], miR-155 [9, 19, 29, 44], let-7b [31, 42], miR-18a [1, 14, 41, 44], and miR-130a [44, 46]. A Carcinogenic Risk Score (CRS) was subsequently calculated and determines whether the overall risk for cancer will be promoted (if positive) or inhibited (if negative).…”

Influence of microRNAs and Long Non-Coding RNAs in Cancer Chemoresistance

“…In essence, over 10% of all reported research findings of miRNA influences in cancer chemoresistance demonstrated that such a phenotype modulation was effected through simultaneous dysregulation of multiple miRNAs, rather than an individual putative chemoresistance miRNA—though no specific miRNA combination was identified as most prevalent by the authors [44,46,47,48,49,62,67,71,76,81,85,88,132,133,158,168,201,203,211,212,213,217,223,224,228,230]. This suggests that miRNA influences on cellular functions also occur at a more complex level, whereby it is a signature dysregulated expression pattern of two (or more) miRNAs that trigger simultaneous downregulation of a specific set of target transcripts leading to an ultimate change in cellular/tissue phenotype.…”

Dysregulated MicroRNA Expression Profiles and Potential Cellular, Circulating and Polymorphic Biomarkers in Non-Hodgkin Lymphoma

“…More recently Yuan et al [57] aimed to investigate the correlation, if any, between circulating miRNAs and chemoresistance in DLBCL patients. At first they showed dysregulated expression of eight miRNAs in serum from 56 DLBCL patients prior to treatment compared to healthy controls: miR-155, miR-200c, miR-130a, miR-125b and miR-21 were upregulated, whereas miR-29c, miR-451 and miR-145 were downregulated.…”

“…Out of the 56 patients, 21 experienced resistance to R-CHOP, and 35 were sensitive to the therapy. The group found that only miR-130a and miR-125b expression was significantly upregulated in the drug resistant group compared to the drug sensitive group and in addition, high levels of miR-130a and miR-125b were associated with a worse prognosis using Kaplan-Meier survival analysis curves, however this was only significant for miR-125b, as miR-130a was not significant after Multivariate Cox regression analysis [57]. Another study showed a correlation between miR-21 knock-down in a DLBCL cell line and decreased resistance to CHOP treatment [65], however Yuan et al [57] were not able to show that increased serum miR-21 levels increased resistance to R-CHOP in their study.…”