Association of miR-21 and miR-335 to microsatellite instability and prognosis in stage III colorectal cancer

Article type: Research Article

Authors: Calvo-López, Tania^{a; 1} | Paz-Cabezas, Mateo^{a; 1} | Llovet, Patricia^a | Ibañez, Maria Dolores^a | Sastre, Javier^a | Alonso-Orduña, Vicente^b | Viéitez, J.Ma.^c | Yubero, Alfonso^d | Vera, Ruth^e | Asensio-Martínez, Elena^f | Garcia-Alfonso, Pilar^g | Aranda, Enrique^h | Diaz-Rubio, Eduardo^a | Perez-Villamil, Beatriz^{a; *}

Affiliations: [a] Genomics and Microarrays Lab, Medical Oncology Department, Instituto de Investigación Sanitaria San Carlos (IdISSC), Hospital Clinico San Carlos, Madrid, Spain | [b] Hospital Universitario Miguel Servet, Instituto de Investigacion Sanitaria de Aragon (IISA), Zaragoza, Spain | [c] Hospital Universitario Central de Asturias, Oviedo, Spain | [d] Hospital Clinico Universitario Lozano Blesa, Zaragoza, Spain | [e] Complejo Hospitalario de Navarra, Pamplona, Spain | [f] Hospital General Universitario de Elche, Alicante, Spain | [g] Hospital Universitario Gregorio Marañon, Madrid, Spain | [h] IMIBIC, CIBERONC, ISCIII, Hospital Universitario Reina Sofia, Cordoba, Spain

Correspondence: [*] Corresponding author: Beatriz Perez-Villamil, Genomics and Microarrays Lab, Medical Oncology Department, Instituto de Investigación Sanitaria San Carlos (IdISSC), Hospital Clinico San Carlos, C/Martin Lagos s/n, Madrid 28040, Spain. Tel.: +34 913303348; E-mail: beatriz.perezvillamil@salud.madrid.org.

Note: [1] These authors contributed equally to this work.

Abstract: BACKGROUND: MicroRNAs (miRs) are frequently altered in colorectal cancer (CRC) and can be used as prognostic factors. OBJECTIVE: To confirm in stage III CRC patients a reported miR signature that was associated to the presence of metastatic disease. To correlate miR expression with microsatellite instability (MSI) and mutations in RAS and BRAF. METHODS: miR-21, miR-135a, miR-206, miR-335 and miR-Let-7a expression was analyzed by RT-qPCR in 150 patients out of the 329 patients used to analyze MSI and RAS and BRAF mutations. Association with disease free survival (DFS) and overall survival (OS) was analyzed. Data was confirmed by a multivariate analysis. RESULTS: MiR-21 high expression (p= 0.034) and miR-335 low expression (p= 0.0061) were significantly associated with MSI-H. A positive trend (p= 0.0624) between miR-135a high expression and RAS mutations was found. Lower miR-21 expression levels are associated with DFS (HR = 2.654, 95% CI: 1.066–6.605, p= 0.036) and a trend with OS (HR = 2.419, 95% CI: 0.749–7.815, p= 0.140). MiR-21 high expression significantly improves DFS of the poor prognosis group (T4 or N2) (p= 0.03). CONCLUSIONS: Association of increased expression of miR-21 and better prognosis in the poor prognostic group may be of interest and could be explored in future prospective clinical trials.

Keywords: Colorectal cancer, survival, microRNAs expression, microsatellite instability, prognostic biomarkers, stage III

DOI: 10.3233/CBM-210353

Journal: Cancer Biomarkers, vol. 34, no. 2, pp. 201-210, 2022