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

Ferran Moratalla-Navarro; Anna Díez-Villanueva; Ainhoa Garcia-Serrano; Adrià Closa; David Cordero; Xavier Solé; Elisabet Guinó; Rebeca Sanz-Pamplona; Xavier Sanjuan; Cristina Santos; Sebastiano Biondo; Ramón Salazar; Victor Moreno

doi:10.3390/cancers15133301

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

Cancers (Basel). 2023 Jun 23;15(13):3301. doi: 10.3390/cancers15133301.

Authors

Ferran Moratalla-Navarro^{1

2

3

4}, Anna Díez-Villanueva^{1

2}, Ainhoa Garcia-Serrano⁵, Adrià Closa⁶, David Cordero^{1

2}, Xavier Solé^{7

8}, Elisabet Guinó^{1

2}, Rebeca Sanz-Pamplona^{1

2

3

9}, Xavier Sanjuan^{2

10}, Cristina Santos^{2

11

12}, Sebastiano Biondo^{2

4

13}, Ramón Salazar^{2

4

11

12}, Victor Moreno^{1

2

3

4}

Affiliations

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, (CI_95% = 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.

Keywords: biomarker; colorectal cancer; microRNA; prognosis.

Grants and funding

This study received funding from Instituto de Salud Carlos III and was co-funded by FEDER funds—a way to build Europe—under the grant PI17-00092; the Spanish Association Against Cancer (AECC) Scientific Foundation under the grant GCTRA18022MORE; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), action Genrisk. ADV received funding from the Catalan Government, under fellowship PERIS SLT017/20/00042.