Identification of a Twelve-microRNA Signature with Prognostic Value in Stage II Microsatellite Stable Colon Cancer

Author:

Moratalla-Navarro Ferran1234ORCID,Díez-Villanueva Anna12,Garcia-Serrano Ainhoa5ORCID,Closa Adrià6ORCID,Cordero David12,Solé Xavier78,Guinó Elisabet12,Sanz-Pamplona Rebeca1239ORCID,Sanjuan Xavier210ORCID,Santos Cristina21112,Biondo Sebastiano2413,Salazar Ramón241112,Moreno Victor1234ORCID

Affiliation:

1. Oncology Data Analytics Program, Catalan Institute of Oncology (ICO), 08908 Barcelona, Spain

2. Colorectal Cancer Group, Bellvitge Biomedical Research Institute (IDIBELL), 08908 Barcelona, Spain

3. Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain

4. Department of Clinical Sciences, Faculty of Medicine, University of Barcelona (UB), 08907 Barcelona, Spain

5. Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, 14186 Stockholm, Sweden

6. Department of Pathology, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands

7. Molecular Biology CORE, Center for Biomedical Diagnostics, Hospital Clinic de Barcelona, 08036 Barcelona, Spain

8. Translational Genomic and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain

9. Lozano Blesa University Hospital, Aragon Health Research Institute (IISA), Aragon I+D Foundation (ARAID), Government of Aragon, 50009 Zaragoza, Spain

10. Department of Pathology, Bellvitge University Hospital, 08907 Barcelona, Spain

11. Oncology Service, Catalan Institute of Oncology (ICO), 08908 Barcelona, Spain

12. Consortium for Biomedical Research in Oncology (CIBERONC), 28029 Madrid, Spain

13. Department of General and Digestive Surgery, Bellvitge University Hospital, 08907 Barcelona, Spain

Abstract

We aimed to identify and validate a set of miRNAs that could serve as a prognostic signature useful to determine the recurrence risk for patients with COAD. Small RNAs from tumors of 100 stage II, untreated, MSS colon cancer patients were sequenced for the discovery step. For this purpose, we built an miRNA score using an elastic net Cox regression model based on the disease-free survival status. Patients were grouped into high or low recurrence risk categories based on the median value of the score. We then validated these results in an independent sample of stage II microsatellite stable tumor tissues, with a hazard ratio of 3.24, (CI95% = 1.05–10.0) and a 10-year area under the receiver operating characteristic curve of 0.67. Functional analysis of the miRNAs present in the signature identified key pathways in cancer progression. In conclusion, the proposed signature of 12 miRNAs can contribute to improving the prediction of disease relapse in patients with stage II MSS colorectal cancer, and might be useful in deciding which patients may benefit from adjuvant chemotherapy.

Funder

Instituto de Salud Carlos III

FEDER

Spanish Association Against Cancer (AECC) Scientific Foundation

Consortium for Biomedical Research in Epidemiology and Public Health

Catalan Government

Publisher

MDPI AG

Subject

Cancer Research,Oncology

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