Detection of circulating tumor cells in liquid biopsies of post-treatment lymphoma

Rafael Cerón-Maldonado, Research Laboratory, Hematology Service, Hospital General de México Dr. Eduardo Liceaga, Secretaría de Salud, Mexico City, México
Amairani Gutiérrez-Nava, Research Laboratory, Hematology Service, Hospital General de México Dr. Eduardo Liceaga, Secretaría de Salud; Department of Diagnostic Biochemistry, Facultad de Estudios Superiores Cuautitlán, Universidad Nacional Autónoma de México (UNAM), Cuautitlán, Estado de México; Mexico City. México
Luisa M. Romero-Ornelas, Research Laboratory, Hematology Service, Hospital General de México Dr. Eduardo Liceaga, Secretaría de Salud;; Graduate Program in Biological Sciences, Biomedicina, UNAM; Mexico City. México
Christian O. Ramos-Peñafiel, Hematology Service, Hospital General de México Dr. Eduardo Liceaga, Secretaría de Salud, Mexico City. México
Adrián De la Cruz-Rosas, Research Laboratory, Hematology Service, Hospital General de México Dr. Eduardo Liceaga, Secretaría de Salud, Mexico City, México
Anel I. García-Laguna, Research Laboratory, Hematology Service, Hospital General de México Dr. Eduardo Liceaga, Secretaría de Salud, Mexico City, México
Iveth Mendoza-Salas, Research Laboratory, Hematology Service, Hospital General de México Dr. Eduardo Liceaga, Secretaría de Salud, Mexico City, México
Efreen H. Montaño-Figueroa, Hematology Service, Hospital General de México Dr. Eduardo Liceaga, Secretaría de Salud, Mexico City. México
Adolfo Martínez-Tovar, Research Laboratory, Hematology Service, Hospital General de México Dr. Eduardo Liceaga, Secretaría de Salud, Mexico City, México
Irma Olarte-Carrillo, Research Laboratory, Hematology Service, Hospital General de México Dr. Eduardo Liceaga, Secretaría de Salud, Mexico City, México

Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive subtype of non-Hodgkin lymphoma. Although the rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen is the standard therapy, up to 30% of patients experience relapse or are refractory. In clinical practice, therapeutic monitoring relies on imaging studies and lacks molecular techniques. Objective: The objective of this study was to evaluate the expression of the molecular biomarkers BCL2, BCL6, EpCAM, VEGFR1, and TWIST1 in circulating tumor cells (CTCs) from DLBCL patients after R-CHOP treatment. Material and methods: The expression of these molecular biomarkers was analyzed in CTCs from 42 post-R-CHOP DLBCL patients, using CD20+ cell enrichment and quantitative reverse transcription polymerase chain reaction for CTCs detection. Results: Significant differences were observed in the expression of BCL2 (p = 0.003), BCL6 (p = 0.001), and VEGFR1 (p = 0.002) compared to healthy controls. The tumor-specific genes EpCAM and TWIST1 were not detected in healthy donors. Overexpression frequencies were as follows: BCL6 28.6% (12/42), BCL2 26.2% (11/42), VEGFR1 16.7% (7/42), TWIST1 7.2% (3/42), and EpCAM 2.4% (1/42). Conclusions: Overexpression of BCL2, BCL6, and VEGFR1, along with the presence of EpCAM and TWIST1 in CTCs from patients with disease progression, supports the relevance of liquid biopsies as a valuable tool to enhance the clinical management of DLBCL patients.

Keywords: Liquid biopsy. Circulating tumor cells. Diffuse large B-cell lymphoma. Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone.