title: Angiomirs expression profiling in diffuse large B-Cell lymphoma.
abstract: Despite advances in treatment, 30% of diffuse large B-cell lymphoma (DLBCL) cases are refractory or relapse after chemoimmunotherapy. Currently, the relationship between angiogenesis and angiomiRs in DLBCL is unknown. We classified 84 DLBCL cases according to stromal signatures and evaluated the expression of pro- and antiangiomiRs in paraffin embedded tissues of DLBCL and correlated them with microvascular density (MVD). 40% of cases were classified as stromal-1, 50% as stromal-2 and 10% were not classified. We observed increased expression of proangiomiRs Let-7f, miR-17, miR-18a, miR-19b, miR-126, miR-130a, miR-210, miR-296 and miR-378 in 14%, 57%, 30%, 45%, 12%, 12%, 56%, 58% and 48% of the cases, respectively. Among antiangiomiRs we found decreased expression of miR-16, miR-20b, miR-92a, miR-221 and miR-328 in, respectively, 27%, 71%, 2%, 44% and 11%. We found association between increased expression of proangiomiRs miR-126 and miR-130a and antiangiomiR miR-328 and the subtype non-GCB. We found higher levels of the antiangiomiRs miR-16, miR-221 and miR-328 in patients with low MVD and stromal-1 signature. IPI and CD34 confirmed independent impact on survival of the study group. None of the above angiomiRs showed significance as biomarker in an independent serum samples cohort of patients and controls. In conclusion, we confirmed association between antiangiomiRs miR-16, miR-221 and miR-328 and stromal-1 signature. Four angiomiRs emerged as potential therapeutic targets: proangiomiRs miR-17, miR-210 and miR-296 and antiangiomiR miR-20b. Although the four microRNAs seem to be important in DLBCL pathogenesis, they were not predictive of DLBCL onset or relapse in the serum independent cohort.
authors.affiliation: Departamento de Oncologia Clínica e Experimental, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Natália M
authors.initials: NM
authors.lastname: Borges
authors.affiliation: Departamento de Oncologia Clínica e Experimental, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Marcela
authors.initials: M
authors.lastname: do Vale Elias
authors.affiliation: Departamento de Oncologia Clínica e Experimental, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Veruska L
authors.initials: VL
authors.lastname: Fook-Alves
authors.affiliation: Departamento de Oncologia Clínica e Experimental, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Tathiana A
authors.initials: TA
authors.lastname: Andrade
authors.affiliation: Departamento de Oncologia Clínica e Experimental, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Marina Lourenço
authors.initials: ML
authors.lastname: de Conti
authors.affiliation: A.C. Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Mariana Petaccia
authors.initials: MP
authors.lastname: Macedo
authors.affiliation: A.C. Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Maria Dirlei
authors.initials: MD
authors.lastname: Begnami
authors.affiliation: A.C. Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Antônio Hugo J F M
authors.initials: AH
authors.lastname: Campos
authors.affiliation: Departamento de Oncologia Clínica e Experimental, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Leina Yukari
authors.initials: LY
authors.lastname: Etto
authors.affiliation: Insper Institute of Education and Research, São Paulo, Brazil.
authors.forename: Adriana Bruscato
authors.initials: AB
authors.lastname: Bortoluzzo
authors.affiliation: Departamento de Patologia, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Alves
authors.affiliation: Department of Hematopathology, MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Ken H
authors.initials: KH
authors.lastname: Young
authors.affiliation: Departamento de Oncologia Clínica e Experimental, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Gisele W B
authors.initials: GW
authors.lastname: Colleoni
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D055806:Microvessels / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000235:genetics*; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D017154:Stromal Cells / Q000473:pathology; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs
keywords: angiogenesis; lymphoma; microRNAs