6533b85ffe1ef96bd12c0f5e

RESEARCH PRODUCT

A novel predictive biomarker of immunotherapy response in metastatic renal cell carcinoma (mRCC): The lymphocyte microRNA expression profile.

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e16109 Background: Predicting which patient with metastatic renal cell carcinoma (mRCC) will benefit from immune checkpoints inhibitors (ICPIs) still remain an issue. Biological factors particular to certain individuals have a clear effect on variation in response. Emerging evidence suggests that small non-coding RNA, such as microRNAs (miRNAs), are critical modulators of numerous cellular processes, including immune surveillance. The main aim of this study was to analyze the lymphocyte miRNA expression profile in mRCC patients and dynamic changes after the treatment with ICPI, in order to investigate the molecular mechanisms and signaling pathways involved in ICPI response and their potential role as predictive biomarker. Methods: Total RNA and miRNAs were isolated from peripheral lymphocytes of 14 mRCC patients, treated with nivolumab as second line. The blood samples were collected before nivolumab treatment (T0) and at progression disease (T1). The quality and quantity of miRNAs were assessed using the miRNeasy Mini Kit, 2100 Bioanalyzer and spectrophotometer NanoDrop ND-1000. Through a TaqMan Low Density Array A human microRNA microarray analysis, the expression profile of 377 lymphocyte miRNAs was analyzed. A cut off of fold change > 2 was considered for up-regulated miRNAs and < 0.3 for down-regulated. The patients were divided into 2 groups: patients with PD within 6 months of treatment (G1), and patients with stable therapy response (RC, RP or SD) over 12 months (G2). Results: Microarray analysis showed a subset of 59 miRNAs involved in several cancer-related processes, including cell cycle regulation, PI3K/Akt, FOXO and HIF-1 signaling pathways, differentially expressed in peripheral lymphocytes of mRCC of G1 and G2 group of patients. Among all miRNAs analyzed, several were deregulated, such as miR-155, miR-22, miR-24, miR-484, miR-335 and miR-492, some up-regulated and others down-regulated. This deregulation of specific miRNAs was different into G1 and G2 groups, and seem to be related with the duration of response to ICPI. Conclusions: Our data, for the first time, study the expression profile of miRNAs in the peripheral lymphocytes, and show a correlation between deregulation of miRNAs and response to Nivolumab. These knowledge could help to identify potential biomarkers predictive of response to ICPIs for the personalization of treatment.