Dysregulation of microRNA Expression After Treatment with Anti-EGFR Antibodies
A team of researchers from Plzeň decided to verify whether treatment with anti-EGFR antibodies changes the expression of selected microRNAs in patients with metastatic colorectal carcinoma (mCRC). They have just published their findings in the autumn issue of the journal Cancer Genomics Proteomics.
microRNA
microRNAs (miRs) are small non-coding RNA molecules 18–25 nucleotides long that play an important role in regulating gene expression. miRs are involved in regulating key processes (proliferation, differentiation, apoptosis, angiogenesis, and cell interactions) related to the development of cancerous diseases. The use of miRs as diagnostic and prognostic biomarkers is being intensely studied.
Evaluated Patient Group
The study included 46 patients who had histologically confirmed metastatic colorectal carcinoma and were simultaneously treated with anti-EGFR monoclonal antibodies (panitumumab or cetuximab) in combination with chemotherapy (FOLFOX or FOLFIRI). None of the patients had previously been treated with anti-EGFR monoclonal antibodies.
Clinical data for the study were obtained from the hospital information system for the years 2010–2019.
The median age of the patients at the start of treatment was 63.6 years (range 37.3–82.5), with men comprising the majority (73.9%). 65.2% of the patients had a primary tumor located in the colon, 58.7% had synchronous metastases, and 78.3% were treated with anti-EGFR antibodies as first-line therapy. 54.3% of the patients were treated with panitumumab and 45.7% with cetuximab. The median progression-free survival (PFS) for the entire cohort was 8.9 months (95% confidence interval [CI] 7.0–12.26) and the median overall survival (OS) was 26.4 months (95% CI 20.1–39.2).
Results
Expression of miRs in Tumor and Surrounding Tissues
A significant difference in the expression of miRs in tumor tissue compared to surrounding tissue was observed for miR-125b, let-7c, and miR-17. Reduced expression was observed in tumor tissue for miR-125b (64.3% of patients; p = 0.0226) and let-7c (69.8% of patients; p = 0.0040). Increased expression was observed for miR-17 (84.6% of patients; p < 0.0001). No significant difference in expression was observed for the other miRs evaluated.
Expression of miRs in relation to response to anti-EGFR antibody treatment
The objective response rate (ORR) was significantly associated with the upregulation of miR-125b (p = 0.0005). The disease control rate (DCR) was significantly associated with the upregulation of miR-125b (p = 0.0383) and let-7c (p = 0.0255) and the downregulation of miR-17 (p = 0.0464). Expression of miR-125b correlated with PFS (p = 0.055) and OS (p = 0.006).
Conclusion
Upregulation of miR-125b is associated with higher ORR and DCR and longer survival. Upregulation of let-7c and downregulation of miR-17 are associated with higher DCR in patients with mCRC treated with anti-EGFR antibodies.
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Source: Fiala O., Šorejs O., Hošek P. et al. Association of miR-125b, miR-17 and let-7c dysregulations with response to anti-epidermal growth factor receptor monoclonal antibodies in patients with metastatic colorectal cancer. Cancer Genomics-Proteomics 2020; 17 (5): 605−613, doi: 10.21873/cgp.20217.
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