Circulating hsa-miR-29c-3p and VEGF-A levels predict the response to FOLFIRI plus aflibercept in elderly metastatic colorectal cancer patients

Marta Toledano-Fonseca ^1,2, María Teresa Cano-Osuna ^1,2, Elena Élez ³

¹Maimonides Biomedical Research Institute of Córdoba (IMIBIC), Medical Oncology Department, Reina Sofia University Hospital, University of Córdoba, Córdoba, Spain.
²Cancer Network Biomedical Research Center (CIBERONC), Madrid, Spain.
³Medical Oncology Department, Vall d'Hebron Barcelona Hospital Campus, Vall d'Hebron Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, CIBERONC, Barcelona, Spain.
⁴Medical Oncology Department, Gregorio Marañón General University Hospital, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Universidad Complutense, Madrid, Spain.
⁵Medical Oncology Department, Hospital de la Santa Creu i Sant Pau, CIBERER, Barcelona, Spain.
⁶Medical Oncology Department, Complejo Hospitalario Universitario de Ourense, Ourense, Spain.
⁷Medical Oncology Department, Pontevedra University Hospital (SERGAS), Galicia Sur Health Research Institute (IISGS), Pontevedra, Spain.
⁸Medical Oncology Department, Hospital Universitario Arnau de Vilanova de Lleida, Lleida, Spain.
⁹Medical Oncology Department, University Hospital Lozano Blesa, Institute for Health Research Aragon (IIS Aragón), Zaragoza, Spain.
¹⁰Medica Oncology Department, Hospital Parc Taulí de Sabadell, Barcelona, Spain.
¹¹Medical Oncology Department, Hospital Lucus Augusti, Lugo, Spain.
¹²Medical Oncology Department, Hospital Universitario Marqués de Valdecilla, IDIVAL, UNICAN, Santander, Spain.
¹³Medical Oncology Department, Hospital Universitario Son Llatzer, Mallorca, Spain.
¹⁴Medical Oncology Department, Hospital Clínico San Carlos, Instituto de Investigación Hospital Clínico San Carlos (IdISSC), Universidad Complutense, Madrid, Spain.

⁰Maimonides Biomedical Research Institute of Córdoba (IMIBIC), Medical Oncology Department, Reina Sofia University Hospital, University of Córdoba, Córdoba, Spain.

European Journal of Clinical Investigation +

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August 1, 2025

View abstract on PubMed

Summary

Biomarkers including miR-29c-3p and VEGF-A can predict treatment response in elderly metastatic colorectal cancer (mCRC) patients receiving FOLFIRI plus aflibercept. This combination improves outcome predictions for personalized therapy.

Area Of Science

Oncology
Translational Medicine
Biomarker Discovery

Background

Metastatic colorectal cancer (mCRC) patients progressing on oxaliplatin-based chemotherapy benefit from FOLFIRI plus aflibercept.
Validated biomarkers for antiangiogenic therapies are needed to guide treatment decisions.
Previous work identified combined plasma VEGF-A, microRNA profile, and clinical characteristics as predictive of outcomes.

Purpose Of The Study

To identify biomarkers of response to FOLFIRI plus aflibercept in elderly mCRC patients.
To evaluate the predictive value of plasma VEGF-A and specific microRNAs in this patient population.

Main Methods

Analysis of plasma samples from 154 elderly mCRC patients (age >70) from the AFEMA trial.
Quantification of circulating VEGF-A and 13 microRNAs (miRNAs) before treatment.
Stratification of patients based on progression-free survival and time-to-treatment failure.

Main Results

VEGF-A and five miRNAs (miR-193-3b, miR-432-5p, miR-29c-3p, miR-93-5p, miR-30a-3p) stratified patients by survival outcomes.
Combining miR-29c-3p with VEGF-A significantly improved prognostic accuracy.
This integrated biomarker approach enhanced patient stratification.

Conclusions

Integrating miR-29c-3p and VEGF-A analysis serves as a valuable biomarker strategy for elderly mCRC patients.
This approach improves outcome prediction for FOLFIRI plus aflibercept therapy.
Personalized therapeutic strategies can be advanced through these predictive biomarkers.

Keywords:

FOLFIRI VEGF‐A aflibercept antiangiogenic therapy circulating miRNAs metastatic colorectal cancer