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.

AngiomiRs: MicroRNAs driving angiogenesis in cancer (Review)

“…In many cases, aberrant expression of miRNAs correlates with worst prognosis, low overall survival and resistance to chemotherapy (10). Diverse studies, focused on miRNA profiles impacting angiogenesis, have been described in almost all human cancers (11,12). miRNAs controlling the angiogenic mechanisms are collectively known as angiomiRs, as they regulate this specialized process in both physiological and pathological conditions ( Fig.…”

MicroRNA‑20b promotes proliferation of H22 hepatocellular carcinoma cells by targeting PTEN

“…For example, miR-20b activity is increased in liver, gastric and breast tumors (18)(19)(20), and it is also a plasmatic marker for non-small cell lung cancer (21). In addition, anti-angiomiR-miR-20b has been described as a potential therapeutic target for refractory large B-cell lymphoma (22). In this study, miR-20b was revealed to promote H22 cell growth by targeting PTEN.…”

Tumor angiogenesis revisited: Regulators and clinical implications

“…Furthermore, miR‐210 expression has been linked to bad prognosis in patients with soft tissue sarcoma, breast, head and neck, and pancreatic cancer (reviewed in). miR‐210 also emerged as a potential therapeutic target in diffuse large B‐cell lymphoma …”

“…miR-210 also emerged as a potential therapeutic target in diffuse large B-cell lymphoma. 276 Whereas miR-210 is widely expressed, other miRs respond to decreased oxygen tension in a more tissue-specific manner. Moreover, HIF-1 expression itself is regulated by several miRs, such as miR-497 in breast carcinoma, 224 adding another level of complexity to the classic hypoxia-regulated gene network.…”