Journal
ONCOTARGET
Volume 8, Issue 31, Pages 50949-50957Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.16435
Keywords
exosomes; mRNA; liquid biopsy; B-cell lymphomas; BCL-6
Categories
Funding
- Fundacion AECC
- [FIS-PI08/0862]
- [SAF2010-20750]
- [RTICC-RD2012/0036/0006]
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Purpose: To determine the feasibility of mRNAs (C-MYC, BCL-XL, BCL-6, NF-kappa beta, PTEN and AKT) in exosomes of plasma as a liquid biopsy method for monitoring and prognostic evolution in B-cell lymphomas. Patients and Methods: Exosomes were isolated from 98 patients with B-cell Lymphoma and 68 healthy controls. mRNAs were analyzed by quantitative PCR. An additional 31 post-treatment samples were also studied. Results: In the general and follicular lymphoma series, the presence of AKT mRNA was associated with poor response to rituximab-based treatment. Patients with first relapse or disease progression showed a lower percentage of PTEN and BCL-XL mRNA. The presence of BCL-6 mRNA was associated with a high death rate. The absence of PTEN mRNA in the general series, and presence of C-MYC mRNA in follicular lymphomas, were associated with short progression-free survival. BCL-6 and C-MYC mRNA were independent prognostic variables of overall survival. C-MYC mRNA may provide prognostic information with respect to overall survival. BCL-XL mRNA and increase of BCL-6 mRNA in post-treatment samples could serve as molecular monitoring markers. Conclusions: This is the first large study to evaluate the prognostic and predictive values of pretreatment tumor-associated mRNA in exosomes. BCL-6 and C-MYC mRNA positivity in pretreatment samples were predictors of worse PFS compared to patients with mRNA negativity. C-MYC mRNA positivity was also a statistically significant predictor of inability to obtain complete response with first-line therapy.
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