全基因组 DNA 甲基化状态是预测转移性结直肠癌二线抗 EGFR 抗体治疗疗效的标志物：EPIC 试验的转化研究。
Genome-wide DNA methylation status is a predictor of the efficacy of anti-EGFR antibodies in the second-line treatment of metastatic colorectal cancer: Translational research of the EPIC trial.
机构信息
Department of Medical Oncology, Tohoku University Hospital, Miyagi, Japan. 4-1 Seiryo-Machi, Aobaku, Sendai, Miyagi, 980-8575, Japan.
Department of Clinical Oncology, Graduate School of Medicine, Tohoku University, Miyagi, Japan. 4-1 Seiryo-Machi, Aobaku, Sendai, Miyagi, 980-8575, Japan.
出版信息
Int J Colorectal Dis. 2024 Jun 11;39(1):89. doi: 10.1007/s00384-024-04659-y.
PURPOSE
The genome-wide DNA methylation status (GWMS) predicts of therapeutic response to anti-epidermal growth factor receptor (EGFR) antibodies in treating metastatic colorectal cancer. We verified the significance of GWMS as a predictive factor for the efficacy of anti-EGFR antibodies in the second-line treatment of metastatic colorectal cancer.
METHODS
Clinical data were obtained from a prospective trial database, and a genome-wide DNA methylation analysis was performed. GWMS was classified into high-methylated colorectal cancer (HMCC) and low-methylated colorectal cancer (LMCC). The patients were divided into subgroups according to the treatment arm (cetuximab plus irinotecan or irinotecan alone) and GWMS, and the clinical outcomes were compared between the subgroups.
RESULTS
Of the 112 patients, 58 (51.8%) were in the cetuximab plus irinotecan arm, and 54 (48.2%) were in the irinotecan arm; 47 (42.0%) were in the HMCC, and 65 (58.0%) were in the LMCC group regarding GWMS. Compared with the LMCC group, the progression-free survival (PFS) was significantly shortened in the HMCC group in the cetuximab plus irinotecan arm (median 1.4 vs. 4.1 months, p = 0.001, hazard ratio = 2.56), whereas no significant differences were observed in the irinotecan arm. A multivariate analysis showed that GWMS was an independent predictor of PFS and overall survival (OS) in the cetuximab plus irinotecan arm (p = 0.002, p = 0.005, respectively), whereas GWMS did not contribute to either PFS or OS in the irinotecan arm.
CONCLUSIONS
GWMS was a predictive factor for the efficacy of anti-EGFR antibodies in the second-line treatment of metastatic colorectal cancer.
目的
全基因组 DNA 甲基化状态（GWMS）可预测抗表皮生长因子受体（EGFR）抗体在转移性结直肠癌治疗中的疗效。我们验证了 GWMS 作为抗 EGFR 抗体二线治疗转移性结直肠癌疗效预测因子的意义。
方法
从一项前瞻性试验数据库中获取临床数据，并进行全基因组 DNA 甲基化分析。GWMS 分为高甲基化结直肠癌（HMCC）和低甲基化结直肠癌（LMCC）。根据治疗臂（西妥昔单抗联合伊立替康或伊立替康单药）和 GWMS 将患者分为亚组，并比较亚组之间的临床结局。
结果
在 112 例患者中，58 例（51.8%）入组西妥昔单抗联合伊立替康组，54 例（48.2%）入组伊立替康组；47 例（42.0%）GWMS 为 HMCC，65 例（58.0%）为 LMCC 组。与 LMCC 组相比，西妥昔单抗联合伊立替康组 HMCC 组的无进展生存期（PFS）明显缩短（中位 1.4 与 4.1 个月，p=0.001，风险比=2.56），而伊立替康组则无显著差异。多变量分析显示，GWMS 是西妥昔单抗联合伊立替康组 PFS 和总生存期（OS）的独立预测因子（p=0.002，p=0.005），而在伊立替康组，GWMS 对 PFS 或 OS 均无影响。
结论
GWMS 是抗 EGFR 抗体二线治疗转移性结直肠癌疗效的预测因子。
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