title: Extracellular tumor-related mRNA in plasma of lymphoma patients and survival implications.
abstract: 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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Department of Medical Oncology, Puerta de Hierro University Hospital, Madrid, Spain.
authors.forename: Vanesa
authors.initials: V
authors.lastname: Garcia
authors.forename: Jose Miguel
authors.initials: JM
authors.lastname: Garcia
authors.forename: Javier
authors.initials: J
authors.lastname: Silva
authors.forename: Paloma
authors.initials: P
authors.lastname: Martin
authors.forename: Cristina
authors.initials: C
authors.lastname: Peña
authors.forename: Gemma
authors.initials: G
authors.lastname: Dominguez
authors.forename: Raquel
authors.initials: R
authors.lastname: Diaz
authors.forename: Mercedes
authors.initials: M
authors.lastname: Herrera
authors.forename: Constanza
authors.initials: C
authors.lastname: Maximiano
authors.forename: Pilar
authors.initials: P
authors.lastname: Sabin
authors.forename: Antonio
authors.initials: A
authors.lastname: Rueda
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Cruz
authors.forename: Jose
authors.initials: J
authors.lastname: Rodriguez
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Canales
authors.forename: Felix
authors.initials: F
authors.lastname: Bonilla
authors.forename: Mariano
authors.initials: M
authors.lastname: Provencio
mesh_terms: D018572:Disease-Free Survival; D005110:Extracellular Space / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000097:blood* / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D009360:Neoplastic Cells, Circulating; D012333:RNA, Messenger / Q000097:blood; D012334:RNA, Neoplasm / Q000097:blood*; D012307:Risk Factors
chemical_list: D012333:RNA, Messenger; D012334:RNA, Neoplasm