Association of MicroRNA-31-5p with Clinical Efficacy of Anti-EGFR Therapy in Patients with Metastatic Colorectal Cancer
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Gene mutations in the pathway downstream of epidermal growth factor receptor (EGFR) are considered to induce resistance to anti-EGFR therapy in colorectal cancer (CRC). We recently reported that microRNA-31 (miR-31)-5p may regulate BRAF activation and play a role in the signaling pathway downstream of EGFR in CRC. Therefore, we hypothesized that miR-31-5p can be a useful biomarker for anti-EGFR therapy in CRC.
We evaluated miR-31-5p expression and gene mutations [KRAS (codon 61 or 146), NRAS (codon 12, 13, or 61), and BRAF (V600E)] in the EGFR downstream pathway in 102 CRC patients harboring KRAS (codon 12 or 13) wild-type who were treated with anti-EGFR therapeutics. Progression-free survival (PFS) and overall survival (OS) were evaluated.
KRAS (codon 61 or 146), NRAS, and BRAF mutations were detected in 6.9, 6.9, and 5.9 % patients, respectively. Compared with CRCs with at least one mutation (n = 20), significantly better PFS (P = 0.0003) but insignificantly better OS were observed in CRCs harboring all wild-type genes (KRAS, NRAS, and BRAF). High miR-31-5p expression was identified in 11 % (n = 11) patients and was significantly associated with shorter PFS (P = 0.003). In CRCs carrying all wild-type genes, high miR-31-5p was associated with shorter PFS (P = 0.027).
High miR-31-5p expression was associated with shorter PFS in patients with CRC treated with anti-EGFR therapeutics. Moreover, in CRCs carrying all wild-type genes, high miR-31-5p was associated with shorter PFS, suggesting that it may be a useful and additional prognostic biomarker for anti-EGFR therapy.
KeywordsOverall Survival Epidermal Growth Factor Receptor BRAF Mutation Colon Cancer Cell Line Epidermal Growth Factor Receptor Pathway
The authors thank the pathology departments of Sapporo Medical University Hospital and Keiyukai Sapporo Hospital for providing the tissue specimens. The authors also thank Enago (www.enago.jp) for English language review. This work was supported by the Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Scientific Research [Grant Numbers: 23790800 (to K.N.) and 23390200 (to Y.S.)], A-STEP (Adaptable & Seamless, Technology Transfer Program through Target-driven R&D) (to K.N.), Sapporo Jikeikai Tomoiki Foundation (to K.N.), Takeda Science Foundation (to K.N.), and Daiwa Securities Health Foundation (to H.I.).
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