OncoTargets and Therapy (Dec 2022)
Overexpression of BCL2, BCL6, VEGFR1 and TWIST1 in Circulating Tumor Cells Derived from Patients with DLBCL Decreases Event-Free Survival
Abstract
Rafael Cerón,1,2 Adolfo Martínez,2 Christian Ramos,3 Adrián De la Cruz,2 Anel García,2 Iveth Mendoza,2 Goujon Palmeros,2 Efreen Horacio Montaño Figueroa,3 Juan Navarrete,4 Silvia Jiménez-Morales,5 Carlos Martinez-Murillo,3 Irma Olarte2 1Posgrado en Ciencias Biológicas, Biomedicina, UNAM, CDMX, México; 2Department of Molecular Biology, Hematology Service, Hospital General de México, “Dr. Eduardo Liceaga”, Mexico City, Mexico; 3Department of Medical Hematology, Hospital General de México, “Dr. Eduardo Liceaga”, Mexico City, Mexico; 4Department of Hematopathology, Hospital General de México, “Dr. Eduardo Liceaga”, Mexico City, Mexico; 5Laboratory of Cancer Genomics, National Institute of Genomic Medicine, Mexico City, MexicoCorrespondence: Irma Olarte, Dr. Balmis 148, Col. Doctores, Alc. Cuauhtémoc, Mexico City, ZC. 06726, Mexico, Tel +525527892000 Ext. 1609, Email [email protected]: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous malignant lymphoid neoplasm and is the most common subtype of non-Hodgkin lymphoma in adults. More than half of patients with DLBCL can achieve remission with standard R-CHOP regimes; however, approximately 30– 40% of patients are still failing this standard therapy, which remains as an important cause of progression and mortality of this disease. It is necessary to have diagnostic and monitoring tools that allow us to improve the accuracy of prognosis in these patients. Circulating tumor cells (CTCs) identification through molecular biomarkers is one of the novel strategies that have been used in other types of cancer, and we aim to use this tool to analyze the potential role in DLBCL.Patients and Methods: We analyzed 138 blood samples of patients with DLBCL, of which CTCs were isolated by density gradient for subsequent detection and quantitation of molecular biomarkers using RT-qPCR with TaqMan probes. Survival analysis was performed using Kaplan–Meier curves.Results: We found overexpression of ABCB1, αSMA, BCL2, BCL6 and VEGFR1 genes, as well as the presence of CK19, EpCAM, KI67, MAGE-A4, SNAIL and TWIST1 genes. CK19 and EpCAM expression were associated with a minor OS (85.7% vs 98.1%, p = 0.002). The overexpression of BCL2, BCL6, VEGFR1 and TWIST1 was related to a minor EFS (p = 0.001).Conclusion: This study showed that in liquid biopsies analyzed, the presence of CTCs can be confirmed through molecular biomarkers, and it has an impact on OS and EFs, making this detection useful in the follow-up and prognosis of patients with DLBCL.Keywords: biomarkers, CTCs, lymphoma, liquid biopsies
