Angiomirs expression profiling in diffuse large B-Cell lymphoma

// Natalia M. Borges 1 , Marcela do Vale Elias 1 , Veruska L. Fook-Alves 1 , Tathiana A. Andrade 1 , Marina Lourenco de Conti 1 , Mariana Petaccia Macedo 2 , Maria Dirlei Begnami 2 , Antonio Hugo J. F. M. Campos 2 , Leina Yukari Etto 1 , Adriana Bruscato Bortoluzzo 3 , Antonio C. Alves 4 , Ken H. Young 5 , Gisele W. B. Colleoni 1 1 Departamento de Oncologia Clinica e Experimental, Universidade Federal de Sao Paulo, Sao Paulo, Brazil 2 A.C. Camargo Cancer Center, Sao Paulo, Brazil 3 Insper Institute of Education and Research, Sao Paulo, Brazil 4 Departamento de Patologia, Universidade Federal de Sao Paulo, Sao Paulo, Brazil 5 Department of Hematopathology, MD Anderson Cancer Center, Houston, Texas, USA Correspondence to: Gisele W.B. Colleoni, e-mail: gcolleoni@unifesp.br Keywords: lymphoma, angiogenesis, microRNAs Received: August 14, 2015       Accepted: November 25, 2015       Published: December 15, 2015 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.