Dados do Trabalho

Título

Expression of microRNAs are associated with survival of glioblastoma patients treated with temozolomide

Introdução

Glioblastoma (GBM) is the most lethal form of primary malignant brain tumor in adults. Despite undergoing conventional therapeutic approaches encompassing surgery, radiotherapy, and temozolomide-based chemotherapy (TMZ), the 5-year overall survival is achieved by less than 5% of patients. Currently, the MGMT methylation status is the main consensual biomarker for TMZ response. Yet, MGMT is not routinely assessed, and other biomarkers are needed.

Objetivo

We aimed to investigate the expression profiling of 827 miRNAs in glioblastomas treated with TMZ and MGMT methylated that had very distinct survival outcomes

Métodos

We selected 11 patients diagnosed with GBM IDH1/2 wild type treated with TMZ. Five had an overall survival (OS) of less than 7,65 months (short-term survival), and six had OS above 30.6 months (termed long-term survivors). The miRNA profile was performed on RNA isolated from FFPE and using nCounter Human v3a miRNA Assay from NanoString. The assessment of differentially expressed miRNAs was done by the nSolver 4.0 software and the Rosalind.bio platform (CEP-HCB: 1775/2019).

Resultados

We observed three differentially expressed micro RNAs between GBM short- and long-term survivors. Two microRNAs were up-regulated (FC: 1.89, p=0.05, FC: 1.85, p=7.51e-3) and one downregulated (FC: -1.51, p=0.05) in short-term survivors. The in-silico analysis revealed a collective count of 3641 predicted targets for these three microRNAs, with 156 genes being concurrently forecasted for all three microRNAs, alongside 17 genes that were validated: NCKAP1, ZNF460, AVL9, NUAK2, POLR1B, GPR180, CBL, TRIM28, FBXW8, CDK6, SLC16A1, HEBP2, NACC1, NR6A1, PTGFRN, MSMO1, and REEP5. Furthermore, the two identified upregulated microRNAs in GBM short-term survivors demonstrated associations GBM outcome.

Conclusões

These three miRNAs could be potential novel prognostic biomarkers for TMZ therapy response in GBM patients.

Palavras-chave

Glioblastoma, Micro-RNAs, NanoString, Biomarkers, Prognosis, Temozolomide.

Financiador do resumo

National Oncology Care Support Program (PRONON), Brazil. Barretos Cancer Hospital, Pio XII Foundation. CNPq Productivity (Brazil).