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Detection of a Circulating MicroRNA Custom Panel in Patients with Metastatic Colorectal Cancer
Published on: March 14, 2019
Panitumumab and cetuximab affect differently miRNA expression in colorectal cancer cells
Romain Chautard1,2, Laetitia Corset2,3, Sajida Ibrahim2
1Department of Hepato-Gastroenterology & Digestive Oncology, CHRU de Tours, France.
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.
Insights
Identifying microRNAs (miRs) involved in anti-EGFR antibody resistance in metastatic colorectal cancer (CRC) is crucial. This study found five specific miRs potentially driving resistance and detected two in patient serum.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Metastatic colorectal cancer (CRC) frequently develops resistance to anti-EGFR monoclonal antibodies.
- Prognostic biomarkers for this resistance are currently lacking.
- MicroRNAs (miRs) are investigated as potential biomarkers and regulators in cancer treatment resistance.
Purpose of the Study:
- To investigate the influence of cetuximab and panitumumab on microRNA expression in colorectal cancer cells.
- To identify miRs that regulate the EGFR pathway and are implicated in resistance to anti-EGFR therapy.
- To detect the expression of specific miRs in the serum of advanced CRC patients undergoing treatment.
Main Methods:
- A miRNome panel of 752 miRs was analyzed.
- Colorectal cancer cells were exposed to cetuximab and panitumumab.
- Bioinformatic analyses were performed to identify miRs interacting with the EGFR pathway.
- Serum samples from patients with advanced CRC were analyzed for miR expression.
Main Results:
- Exposure to cetuximab and panitumumab significantly altered the expression of 17 out of 752 miRs.
- Six of these modulated miRs were found to interact with downstream elements of the EGFR pathway.
- Five novel miRs (miR-95-3p, miR-139-5p, miR-145-5p, miR-429, miR-1247-5p) were identified as potential contributors to anti-EGFR antibody resistance.
- miR-139-5p and miR-145-5p were detected in the serum of patients with metastatic CRC.
Conclusions:
- Five specific microRNAs may play a role in the resistance of colorectal cancer to anti-EGFR monoclonal antibodies.
- The identified miRs represent potential novel biomarkers for predicting or overcoming treatment resistance.
- The presence of miR-139-5p and miR-145-5p in patient serum suggests their potential utility as circulating biomarkers in metastatic CRC.
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