Epidermal growth factor receptor (EGFR) gene promoter methylation and cetuximab treatment in colorectal cancer patients.
Epidermal growth factor receptor (EGFR) gene promoter methylation and cetuximab treatment in colorectal cancer patients.
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DOI：
10.1038/bjc.2011.161
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发表时间：
2011-05-24
影响因子：
8.8
通讯作者：
Cascinu, S.
中科院分区：
文献类型：
--
作者：
Scartozzi, M.;Bearzi, I.;Mandolesi, A.;Giampieri, R.;Faloppi, L.;Galizia, E.;Loupakis, F.;Zaniboni, A.;Zorzi, F.;Biscotti, T.;Labianca, R.;Falcone, A.;Cascinu, S.
表皮生长因子受体（EGFR）启动子甲基化可能是肿瘤细胞中EGFR表达缺失的原因。本研究的主要目的是验证接受伊立替康和西妥昔单抗化疗的转移性结直肠癌患者中EGFR基因启动子甲基化与临床结局之间的可能相关性。对伊立替康-西妥昔单抗治疗患者的结直肠样本进行EGFR启动子甲基化和EGFR免疫组化分析。分析了52例患者。30例患者（58%）显示EGFR启动子高甲基化。在EGFR启动子甲基化和EGFR启动子非甲基化的患者中，我们分别观察到3例（10%）和13例（59%）患者的部分缓解（P=0.03），EGFR启动子甲基化和EGFR启动子非甲基化肿瘤患者中分别有19例（63%）和2例（9%）患者的疾病进展（P=0.0001）。EGFR启动子甲基化肿瘤患者的中位无进展生存期为2.4个月，EGFR启动子非甲基化肿瘤患者的中位无进展生存期为7.4个月（P<0.0001;图1）。EGFR启动子甲基化肿瘤患者的中位总生存期为6.1个月，EGFR启动子非甲基化肿瘤患者的中位总生存期为17.8个月（P<0.0001;图2）。结论：EGFR启动子甲基化，在更大的数据集确认后，可能代表了进一步研究EGFR作为结直肠癌治疗靶点的有价值的资产。
Epidermal growth factor receptor (EGFR) promoter methylation may be responsible for the loss of EGFR expression in neoplastic cells. The primary aim of our study was to verify a possible correlation between EGFR gene promoter methylation and clinical outcome in metastatic colorectal cancer patients receiving chemotherapy with irinotecan and cetuximab. Colorectal samples from patients treated with irinotecan–cetuximab were analysed for EGFR promoter methylation and EGFR immunohistochemistry. Fifty-two patients were analysed. Thirty patients (58%) showed EGFR promoter hypermethylation. In EGFR promoter methylated and EGFR promoter unmethylated patients, we observed a partial response in 3 (10%) and 13 (59%) patients, respectively (P=0.03), progressive disease was obtained in 19 (63%) and 2 (9%) patients, respectively, with EGFR promoter methylated and EGFR promoter unmethylated tumours (P=0.0001). Median progression-free survival was 2.4 months in patients showing EGFR promoter methylated tumours and 7.4 months for those who had EGFR promoter unmethylated tumours (P<0.0001; Figure 1). Median overall survival was 6.1 months in patients showing EGFR promoter methylated tumours and 17.8 months for those who had EGFR promoter unmethylated tumours (P<0.0001; Figure 2). CONCLUSION: EGFR promoter hypermethylation, after confirmation in larger data set, may represent a valuable asset in further studies investigating EGFR as a therapeutic target in colorectal cancer.
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DOI：
10.1073/pnas.93.18.9821
发表时间：
1996-09-03
影响因子：
11.1
作者：
Herman, JG;Graff, JR;Baylin, SB
通讯作者：
Baylin, SB
影响因子：
3.8
作者：
Scartozzi M;Bearzi I;Mandolesi A;Pierantoni C;Loupakis F;Zaniboni A;Negri F;Quadri A;Zorzi F;Galizia E;Berardi R;Biscotti T;Labianca R;Masi G;Falcone A;Cascinu S
通讯作者：
Cascinu S
影响因子：
51.1
作者：
Moroni, M;Veronese, S;Bardelli, A
通讯作者：
Bardelli, A
影响因子：
158.5
作者：
Jonker, Derek J.;O'Callaghan, Chris J.;Moore, Malcolm J.
通讯作者：
Moore, Malcolm J.
影响因子：
8
作者：
Karpf, AR;Jones, DA
通讯作者：
Jones, DA