mRNA in exosomas as a liquid biopsy in non-Hodgkin Lymphoma: a multicentric study by the Spanish Lymphoma Oncology Group
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Mariano Provencio1,*, Marta Rodríguez1, Blanca Cantos1, Pilar Sabín2, Cristina Quero3, Francisco R. García-Arroyo4, Antonio Rueda5, Constanza Maximiano1, Delvys Rodríguez-Abreu6, Antonio Sánchez1, Javier Silva1 and Vanesa García1,7,*, on behalf of GOTEL (Spanish Lymphoma Oncology Group)
1Department of Medical Oncology, IDIPHIM, University Hospital Puerta de Hierro Research Institute, Madrid, Spain
2Department of Medical Oncology, Gregorio Marañon Hospital, Madrid, Spain
3Department of Radiotherapy, Virgen de la Victoria Clinic University Hospital, Málaga, Spain
4Department of Medical Oncology, Pontevedra Hospital, Pontevedra, Spain
5Department of Medical Oncology, Costa del Sol Hospital, Marbella, Spain
6Department of Medical Oncology, Gran Canaria University Hospital, Las Palmas de Gran Canaria, Spain
7Molecular Oncology Laboratory, IdISSC, Clinico San Carlos University Hospital, Madrid, Spain
*These authors have contributed equally to this work
Mariano Provencio, email: email@example.com
Vanesa García, email: firstname.lastname@example.org
Keywords: exosomes, mRNA, liquid biopsy, B-cell lymphomas, BCL-6
Received: September 14, 2016 Accepted: February 27, 2017 Published: March 22, 2017
Purpose: To determine the feasibility of mRNAs (C-MYC, BCL-XL, BCL-6, NF-κβ, 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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