Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster Display session 3

1877 - Advanced clear-cell renal cell carcinoma (accRCC): association of microRNAs (miRNAs) with molecular subtypes, mRNA targets and outcome.

Date

30 Sep 2019

Session

Poster Display session 3

Topics

Renal Cell Cancer

Presenters

Annelies Verbiest

Citation

Annals of Oncology (2019) 30 (suppl_5): v356-v402. 10.1093/annonc/mdz249

Authors

A.T.L. Verbiest1, V. Van Hoef2, D. Lambrechts3, C. Rodriguez Antona4, O. Grana-Castro4, L. Inglada-Perez4, M. Albersen5, M. Baldewijns6, A. Laenen7, P. Schoeffski1, A. Wozniak8, G. Couchy9, S. Caruso9, J. Zucman-Rossi9, B. Beuselinck1

Author affiliations

  • 1 General Medical Oncology, University Hospitals Leuven, 3000 - Leuven/BE
  • 2 Bioinformatics Expert Center, VIB, 3000 - Leuven/BE
  • 3 Center For Cancer Biology, VIB, 3000 - Leuven/BE
  • 4 Human Cancer Genetics Programme, CNIO, Madrid/ES
  • 5 Urology, University Hospitals Leuven, 3000 - Leuven/BE
  • 6 Imaging And Pathology, University Hospitals Leuven, 3000 - Leuven/BE
  • 7 Biostatistics And Statistical Bioinformatics Center, KU Leuven, 3000 - Leuven/BE
  • 8 Laboratory Of Experimental Oncology, KU Leuven, 3000 - Leuven/BE
  • 9 Umrs-1138, INSERM, 75006 - Paris/FR
More

Resources

Abstract 1877

Background

Based on mRNA expression, accRCC can be divided in four molecular subtypes (ccrcc1-4), associated with prognosis, angiogenic signature, immune phenotype and therapy response. miRNAs are master regulators of mRNA function. We assessed the correlation of miRNA expression with (1) ccrccc1-4 subtypes, (2) mRNA targets and (3) outcome.

Methods

We performed miRNome analysis of 128 accRCC. (1) Unsupervised hierarchical clustering was done using 50 miRNAs with the most variable expression across all samples. Results were validated on TCGA data (n = 255). (2) For miRNAs with subtype-specific expression, we performed pathway analysis of predicted mRNA targets (IPA, KEGG) and assessed target-downregulation in TCGA. (3) We used Cox regression to correlate miRNA expression with overall survival (OS) since diagnosis. Hazard ratios (HR) were correlated with subtype-specific expression (Pearson).

Results

(1) Samples separated in two miRNA clusters, that partially overlapped with molecular subtypes. Cluster 1 consisted of 69% favourable subtypes (ccrcc2 or 3), cluster 2 of 77% unfavourable (ccrcc1 or 4) (p < 2.2e-16). (2) Pathway analysis of predicted mRNA targets and targets suppressed in TCGA, suggested that favourable subtypes exhibit more angiogenic signaling, whereas unfavourable subtypes activate pathways involved in tumor invasiveness. (3) Several miRNAs were significantly associated with OS. There was a robust correlation in the entire dataset between HR for OS and differential expression between favourable/unfavourable subtypes (r = 0.322; p < 0.0001).Table:

973P

miRNASubtype-specific expression log2FoldChange <0: higher in ccrcc1 or -4 (unfavourable) log2FoldChange >0: higher in ccrcc2 or -3 (favourable)*p<0.05 ** false discovery rate <0.05Overall survival (hazard ratio)
182-5p-1,43**1,25**
3529-3p-1,42**1,37**
335-3p-1,33**1,25**
34c-5p-1,22**1,25**
193b-3p-1,17**1,31**
370-3p-1,07**1,16**
199b-5p-1,05**1,26**
21-3p-0,89**1,47**
574-5p-0,89**1,40**
4792-0,88**0,88*
let-7i-5p-0,81**1,66**
652-3p-0,75**1,39**
1301-3p-0,70**1,39**
222-3p-0,66**1,31*
320a-0,63**1,28**
425-5p-0,62**1,66**
149-5p-0,61**1,32*
146b-5p-0,54*1,49**
193b-5p-0,491,21**
185-5p-0,49**1,42**
21-5p-0,42*1,68**
7641-0,330,80**
320b-0,281,25**
1260b-0,150,79**
44540,150,80**
6880-5p0,250,64**
27b-3p0,36**0,71*
1260a0,380,73**
79770,390,73**
23b-3p0,48**0,81**
23920,550,80**
194-5p0,55*0,74**
30c-5p0,70**0,78*
190a-5p0,86**0,83**
204-5p1,23**0,71**
135a-5p1,37**0,86**

Conclusions

accRCC molecular subtypes exhibit different miRNA expression patterns. Differentially expressed miRNAs are implicated in pathways driving tumor biology and strongly correlated with OS. These findings underscore the robustness of the molecular subtypes and are, to the best of our knowledge, the first to show an association of global miRNome expression with outcome.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Fonds Wetenschappelijk Onderzoek Vlaanderen.

Disclosure

M. Albersen: Research grant / Funding (self): Ipsen. B. Beuselinck: Advisory / Consultancy, Research grant / Funding (self): Bristol Meyers Squibb; Speaker Bureau / Expert testimony: Ipsen; Speaker Bureau / Expert testimony: Merck; Research grant / Funding (self): Pfizer. All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.