Panitumumab and Cetuximab Affect Differently Mirna Expression in Colorectal Cancer Cells

Abstract

Background & aim: Resistance to anti-EGFR monoclonal antibodies in metastatic colorectal cancer (CRC) is frequent and prognostic biomarkers are lacking. MicroRNAs (miR) are good candidates in this context. We aimed to characterize cetuximab and panitumumab exposure influence on miR expression in colorectal cancer cells to identify those regulating the EGFR pathway and implicated in resistance to treatment. Finally, we aimed to identify miR expression in serum of patients with advanced CRC treated with cetuximab or panitumumab. Results: Cetuximab and panitumumab exposure induced significant expression variations of 17 miR out of a miRnome panel of 752. Six of those miR interacted with at least one downstream element of the EGFR pathway. Conclusion: After the bioinformatics two-phase process, five miR rarely described before could be potential actors of anti-EGFR monoclonal antibody resistance: miR-95-3p, miR-139-5p, miR-145-5p, miR-429 and miR-1247-5p. In vivo, we detected the expression of miR-139-5p and miR-145-5p in serum of patients with metastatic CRC.

Keywords:

• biomarkers
• cell lines
• epidermal growth factor receptor
• metastatic colorectal cancer
• microRNA
• monoclonal antibodies
• serum

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/bmm-2020-0520

Author contributions

W Raoul, N Baroukh and T Lecomte initiated and designed the study. R Chautard, L Corset, S Ibrahim, C Desvignes and M Gueguinou performed the experiments and/or analyzed the data. R Chautard, T Lecomte and W Raoul interpreted the data and drafted the original manuscript and the reviewed version. L Corset, S Ibrahim, G Paintaud, N Baroukh, C Desvignes and M Guéguinou reviewed and improved the manuscript. All authors read and approved the final manuscript.

Acknowledgements

The authors thank V André and V Massot from CHRU Tours for technical assistance. They thank S Marouillat from iBrain for technical advice.

Financial & competing interests disclosure

G Paintaud reports grants from Chugai, Shire/Takeda, Amgen, Merck, Lilly, Novartis, Roche Pharma, Genzyme/Sanofi. T Lecomte reports consulting honorarium for Sanofi, Bayer and Servier and educational presentations for Eli Lilly and Servier. EA7501 and EA4245 are implicated in the program ‘Investissements d’avenir’ LabEx MAbImprove, grant agreement ANR-10-LABX-53 (French National Research Agency). This project was supported by grants on behalf of the following French department committees of Ligue Contre le Cancer Grand-Ouest: 16 (Charente), 37 (Indre-et-Loire), 49 (Maine-et-Loire) and 72 (Sarthe). M Guéguinou is a recipient of a 3-year postdoctoral grant from Région Centre – Val de Loire. R Chautard was a recipient of a one-year fellowship grant ‘année recherche’ from CHRU Tours. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

G Paintaud reports grants from Chugai, Shire/Takeda, Amgen, Merck, Lilly, Novartis, Roche Pharma, Genzyme/Sanofi. T Lecomte reports consulting honorarium for Sanofi, Bayer and Servier and educational presentations for Eli Lilly and Servier. EA7501 and EA4245 are implicated in the program ‘Investissements d’avenir’ LabEx MAbImprove, grant agreement ANR-10-LABX-53 (French National Research Agency). This project was supported by grants on behalf of the following French department committees of Ligue Contre le Cancer Grand-Ouest: 16 (Charente), 37 (Indre-et-Loire), 49 (Maine-et-Loire) and 72 (Sarthe). M Guéguinou is a recipient of a 3-year postdoctoral grant from Région Centre – Val de Loire. R Chautard was a recipient of a one-year fellowship grant ‘année recherche’ from CHRU Tours. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.