Abstract 5089
Background
The variability of clinical response to immune checkpoint inhibitors in RCC patients makes necessary the discovery of predictive biomarkers for patient selection. Emerging evidence has revealed a multitude of silenced genes and deregulated signalling pathways. These findings point towards extensive microRNAs (miRNAs) regulation and imply epigenetic reprogramming as a key feature of RCC. The aim of this study was to analyze the peripheral lymphocyte miRNA expression profile in metastatic RCC patients undergoing nivolumab treatment, to identify a lymphocyte miRNA signature specifically expressed in patients with partial or complete response (RP; RC) >12 months.
Methods
miRNAs were isolated from peripheral lymphocytes of 18 mRCC patients treated with nivolumab as 2nd line. The blood samples were collected before starting treatment (T0) and after 4 weeks (T1). The expression profile of 377 miRNAs was analyzed, with a cut off of fold change >2 for up-regulated and <0.3 for down-regulated miRNAs. Patients were divided into 2 groups: i) patients with disease progression (PD) within 6 months of treatment (P1); ii) patients with durable response (SD, RP, RC) >12 months (P2).
Results
Microarray analysis showed several differentially expressed miRNAs in peripheral lymphocytes of P1 and P2, involved in RCC signaling pathways such as VHL-HIF, PI3K/Akt, PTEN and WNT-β-catenin. Surprisingly, patients with RC > 12 months showed a subset of 8 miRNAs (miR-24, miR-22, miR-99a, miR-708, miR-339, miR-335, miR-214, miR-194) specifically induced by nivolumab treatment. These miRNAs are silenced or downregulated in RCC. This could explain the exceptional up-regulation in long-responder patients, evident already after 4 weeks of treatment.
Conclusions
Our study for the first time analyzed the miRNA expression profile in peripheral lymphocytes and showed the exceptional up-regulation of a specific subset of miRNA only in RCC patients with durable (<12 months) and complete response to nivolumab treatment. These findings could help to identify novel predictive biomarkers urgently needed to guide clinical decision-making in RCC patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Department of Surgical, Oncological and Oral Sciences, University of Palermo.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
4900 - Molecular profiling and prognostic significance of TP53 mutations in Diffuse Large B Cell Lymphoma: identifying a high-risk subgroup
Presenter: Yuan-Kai Shi
Session: Poster Display session 3
Resources:
Abstract
3809 - Differential expression of various miRNAs in Pediatric Cytogenetically Normal Acute Myeloid Leukemia (CN-AML)
Presenter: Vikas Gaur
Session: Poster Display session 3
Resources:
Abstract
4750 - Circulating tumour cells in head and neck and non-small cell lung cancer
Presenter: Kenneth O'Byrne
Session: Poster Display session 3
Resources:
Abstract
3704 - OX40/OX40L protein expression in Non-small cell lung cancer and its role in clinical outcome and relationships with other immune biomarkers
Presenter: Xiaoshen Zhang
Session: Poster Display session 3
Resources:
Abstract
2235 - Effect of Serum Survivin on Survival among Non-Small Cell Lung Cancer Patients; NCI Experience
Presenter: Reham Rashed
Session: Poster Display session 3
Resources:
Abstract
2788 - Enhanced performance of prognostic estimation from TCGA RNAseq data using transfer learning.
Presenter: Helene Vanacker
Session: Poster Display session 3
Resources:
Abstract
4689 - Analysis of Circulating Tumor DNA for Early Relapse Detection in Stage III Colorectal Cancer After Adjuvant Chemotherapy
Presenter: Samuel Jacobs
Session: Poster Display session 3
Resources:
Abstract
1454 - Ascites-derived circulating microRNAs as potential diagnostic biomarkers of gastric cancer-associated malignant ascites
Presenter: Hye Sook Han
Session: Poster Display session 3
Resources:
Abstract
5574 - Results from TRIO030, a Pre-Surgical Tissue-Acquisition Study to Evaluate Molecular Alterations in Human Breast Cancer Tissue Following Short-Term Exposure to the Androgen Receptor Antagonist Darolutamide
Presenter: Hsiao-Wang Chen
Session: Poster Display session 3
Resources:
Abstract
1787 - JMJD2A is a novel epigenetic factor of chemotherapeutic susceptibility in gastric cancer
Presenter: Yasushi Sato
Session: Poster Display session 3
Resources:
Abstract