García, VanesaGarcía, José MiguelSilva, JavierMartín, PalomaPeña, CristinaDomínguez, GemmaDíaz, RaquelHerrera, MercedesMaximiano, ConstanzaSabin, PilarRueda Domínguez, AntonioCruz, Miguel ÁngelRodríguez, JoséCanales, Miguel ÁngelBonilla, FélixProvencio, Mariano2012-11-142012-11-142009-12-15García V, García JM, Silva J, Martín P, Peña C, Domínguez G, et al. Extracellular tumor-related mRNA in plasma of lymphoma patients and survival implications. PLoS ONE; 4(12):e8173http://hdl.handle.net/10668/621Journal Article; Research Support, Non-U.S. Gov't;BACKGROUND We studied anomalous extracellular mRNAs in plasma from patients with diffuse large B-cell lymphoma (DLBCL) and their survival implications. mRNAs studied have been reported in the literature as markers of poor (BCL2, CCND2, MYC) and favorable outcome (LMO2, BCL6, FN1) in tumors. These markers were also analyzed in lymphoma tissues to test possible associations with their presence in plasma. METHODOLOGY/PRINCIPAL FINDINGS mRNA from 42 plasma samples and 12 tumors from patients with DLBCL was analyzed by real-time PCR. Samples post-treatment were studied. The immunohistochemistry of BCL2 and BCL6 was defined. Presence of circulating tumor cells was determined by analyzing the clonality of the immunoglobulin heavy-chain genes by PCR. In DLBCL, MYC mRNA was associated with short overall survival. mRNA targets with unfavorable outcome in tumors were associated with characteristics indicative of poor prognosis, with partial treatment response and with short progression-free survival in patients with complete response. In patients with low IPI score, unfavorable mRNA targets were related to shorter overall survival, partial response, high LDH levels and death. mRNA disappeared in post-treatment samples of patients with complete response, and persisted in those with partial response or death. No associations were found between circulating tumor cells and plasma mRNA. Absence of BCL6 protein in tumors was associated with presence of unfavorable plasma mRNA. CONCLUSIONS/SIGNIFICANCE Through a non-invasive procedure, tumor-derived mRNAs can be obtained in plasma. mRNA detected in plasma did not proceed from circulating tumor cells. In our study, unfavorable targets in plasma were associated with poor prognosis in B-cell lymphomas, mainly MYC mRNA. Moreover, the unfavorable targets in plasma could help us to classify patients with poor outcome within the good prognosis group according to IPI.enEspacio ExtracelularInmunohistoquímicaEstimación de Kaplan-MeierLinfoma de Células B Grandes DifusoCélulas Neoplásicas CirculantesARN MensajeroARN NeoplásicoFactores de riesgoSupervivencia sin EnfermedadMedical Subject Headings::Anatomy::Tissues::Body Fluid Compartments::Extracellular SpaceMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Cytological Techniques::Histocytochemistry::ImmunohistochemistryMedical Subject Headings::Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Statistics as Topic::Survival Analysis::Kaplan-Meier EstimateMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Histologic Type::Lymphoma::Lymphoma, Non-Hodgkin::Lymphoma, B-Cell::Lymphoma, Large B-Cell, DiffuseMedical Subject Headings::Anatomy::Cells::Neoplastic Cells, CirculatingMedical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, MessengerMedical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, NeoplasmMedical Subject Headings::Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Epidemiologic Factors::Causality::Risk FactorsMedical Subject Headings::Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Statistics as Topic::Survival Analysis::Disease-Free Survivalresearch article20016842open access10.1371/journal.pone.00081731932-6203PMC2788245