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e-Poster Display Session

12P - The correlation between non-coding RNA and response rate to immune-checkpoint inhibitors

Date

09 Dec 2020

Session

e-Poster Display Session

Presenters

Dmitrii Shek

Citation

Annals of Oncology (2020) 31 (suppl_7): S1417-S1424. 10.1016/annonc/annonc389

Authors

D. Shek1, S. Read2, A. Nagrial3, M. Carlino4, J. George5

Author affiliations

  • 1 Western Sydney University - School of Medicine, 2148 - Campbelltown/AU
  • 2 Westmead Institute for Medical Research, Blacktown/AU
  • 3 Westmead Hospital, Blacktown/AU
  • 4 Melanoma Institute Australia, Wollstonecraft/AU
  • 5 The University of Sydney, Westmead/AU
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Abstract 12P

Background

Immune-checkpoint inhibitors (ICIs) have revolutionized clinical oncology in recent years. ICIs are monoclonal antibodies (mAbs) that block inhibitory CTLA-4 and PD-1 signalling pathways and boost cytotoxic T cell antitumor activity. Currently, there is a lack of knowledge regarding factors associated with ICI efficacy and safety. Non-coding RNAs (ncRNAs) are abundant (up to 70% of the human genome) regulators of gene expression, with proven abilities to promote cancer drug resistance. This study aims to determine an association between tumour ncRNA and response to ICI therapy.

Methods

Gene expression data was downloaded from the NCBI GEO database. Effect-size (standardized mean difference [SMD]) was calculated using Hedges’ g method and further meta-analysis was conducted in Stata v16 software. DAVID online bioinformatics tool was used to determine proteins and pathways associated with abnormally expressed ncRNAs.

Results

We identified two datasets derived from patients undergoing anti-PD-1 mAb (nivolumab) therapy: GSE79691 (metastatic melanoma [MM]) and GSE67501 (renal cell carcinoma [RCC]). Both studies evaluated RNA from formalin-fixed paraffin embedded (FFPE) specimens. MiR-27B (p=0.02) and miR-let7D (p=0.003) were significantly higher among non-responders to ICI therapy compared to responders in both datasets. In particular, SMD was 4.57 (miR-27B) and 3.9 (miR-let7D) higher among non-responders in both studies with low study heterogeneity scores (I2=22.67% and T2=0.36). In comparison, analysis of datasets GSE99898 (MM) and GSE74174 (RCC) using kinase inhibitors found no significant association between treatment response and the aforementioned microRNAs. Because miR-27B and miR-let7D influence PI3K/Akt and Wnt/β-catenin signalling pathways, further studies are required to validate whether these microRNAs modulate cancer progression in general or are unique to ICI therapy response.

Conclusions

We have established that miR-27B and miR-let7D are increased among non-responders to ICI therapy supporting their possible predictive role for ICI therapeutic response.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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