Association of MicroRNA-31-5p with Clinical Efficacy of Anti-EGFR Therapy in Patients with Metastatic Colorectal Cancer
Association of MicroRNA-31-5p with Clinical Efficacy of Anti-EGFR Therapy in Patients with Metastatic Colorectal Cancer
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DOI：
10.1245/s10434-014-4264-7
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发表时间：
2015-08-01
影响因子：
3.7
通讯作者：
Shinomura, Yasuhisa
中科院分区：
文献类型：
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作者：
Igarashi, Hisayoshi;Kurihara, Hiroyoshi;Shinomura, Yasuhisa
表皮生长因子受体(EGFR)下游的基因突变被认为是导致结直肠癌(CRC)对抗EGFR治疗产生抵抗的原因。我们最近报道，microRNA-31(miR-31)-5p可能调节BRAF的激活，并在结直肠癌EGFR下游的信号通路中发挥作用。因此，我们假设miR-31-5p可以作为抗EGFR治疗的一个有用的生物标志物。我们评估了102例接受抗EGFR治疗的野生型大肠癌患者的miR-31-5p的表达和EGFR下游通路的基因突变[KRAS(密码子61或146)、NRAS(密码子12、13或61)和BRAF(V600E)]。无进展生存期(PFS)和总生存期(OS)。KRAS(密码子61或146)、NRAS和BRAF突变分别为6.9%、6.9%和5.9%。与至少有一个突变的CRC(n=20)相比，携带全部野生型基因(KRAS、NRAS和BRAF)的CRC的PFS显著改善(P=0.0003)，但OS无显著改善。11例患者中有11例miR-31-5p高表达，并与较短的PFS显著相关(P=0.003)。在携带所有野生型基因的大肠癌中，miR-31-5p的高表达与较短的PFS相关(P=0.027)。在接受抗EGFR治疗的结直肠癌患者中，miR-31-5p的高表达与较短的PFS相关。此外，在携带所有野生型基因的CRC中，高miR-31-5p与较短的PFS相关，这表明它可能是抗EGFR治疗的有用和额外的预后生物标志物。
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.