Department of Surgery, Tung' Taichung MetroHarbor Hospital, Taichung, Taiwan, Republic of China; Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan, Republic of China.
Cancer. 2013 Sep 15;119(18):3367-76. doi: 10.1002/cncr.28220. Epub 2013 Jun 24.
Lung cancers in women, in nonsmokers, and in patients with adenocarcinoma from Asia have more prevalent mutations in the epidermal growth factor receptor (EGFR) gene than their counterparts. However, the etiology of EGFR mutations in this population remains unclear. The authors hypothesized that the human papillomavirus (HPV) type 16/18 (HPV16/18) E6 oncoprotein may contribute to EGFR mutations in Taiwanese patients with lung cancer.
One hundred fifty-one tumors from patients with lung cancer were enrolled to determine HPV16/18 E6 and EGFR mutations using immunohistochemistry and direct sequencing, respectively. Levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) in lung tumors and cells were evaluated using immunohistochemistry and liquid chromatography-mass spectrometry/mass spectrometry. An supF mutagenesis assay was used to determine H2 O2 -induced mutation rates of lung cancer cells with or without E6 expression.
Patients with E6-positive tumors had a greater frequency of EGFR mutations than those with E6-negative tumors (41% vs 20%; P = .006). Levels of 8-oxo-dG were correlated with EGFR mutations (36% vs 16%; P = .012). Two stable clones of E6-overexpressing H157 and CL-3 cells were established for the supF mutagenesis assay. The data indicated that the cells with high E6 overexpression had higher H2 O2 -induced SupF gene mutation rates compared with the cells that expressed lower levels of E6 and compared with vector control cells.
HPV16/18 E6 may contribute in part to EGFR mutations in lung cancer, at least in the Taiwanese population.
女性、不吸烟人群以及来自亚洲的腺癌患者的肺癌中，表皮生长因子受体（EGFR）基因突变比其对应人群更为常见。然而，该人群中 EGFR 突变的病因仍不清楚。作者假设人乳头瘤病毒（HPV）16/18 型（HPV16/18）E6 癌蛋白可能导致台湾肺癌患者的 EGFR 突变。
使用免疫组织化学和直接测序法分别检测 151 例肺癌患者肿瘤中的 HPV16/18 E6 和 EGFR 突变。使用免疫组织化学和液相色谱-质谱/质谱法评估肺癌组织和细胞中的 8-氧-7,8-二氢-2'-脱氧鸟苷（8-氧-dG）水平。使用 supF 诱变试验测定有无 E6 表达的肺癌细胞中 H2 O2 诱导的突变率。
E6 阳性肿瘤患者的 EGFR 突变频率高于 E6 阴性肿瘤患者（41% vs. 20%；P = 0.006）。8-氧-dG 水平与 EGFR 突变相关（36% vs. 16%；P = 0.012）。为 supF 诱变试验建立了两个稳定的 E6 过表达 H157 和 CL-3 细胞克隆。数据表明，与表达较低水平 E6 的细胞和载体对照细胞相比，高 E6 过表达的细胞具有更高的 H2 O2 诱导 SupF 基因突变率。
HPV16/18 E6 可能部分导致肺癌中的 EGFR 突变，至少在台湾人群中如此。
