人乳头瘤病毒与NSCLC相关性探讨

发布时间：2018-11-07 11:52

【摘要】：目的探讨人乳头瘤病毒(HPV)感染与非小细胞肺癌(NSCLC)发病相关性;分析HPV感染与NSCLC临床病理特征和多种基因突变之间的关系。方法收集NSCLC 264例原发灶和65例转移灶的石蜡包埋组织标本。选择264例原发灶邻近的上皮组织(癌旁对照组)和12例肺良性组织分别作为对照。采用免疫组化En Vision二步法检测HPV L1蛋白。选择109例NSCLC标本采用实时荧光定量PCR(RTPCR)法检测HPV16/18 L1基因序列;90例肺腺癌组织同时行EGFR、ALK、KRAS、BRAF基因状态RT-PCR法检测。结果NSCLC原发灶与转移灶HPV L1蛋白检测阳性率相近。NSCLC原发灶HPV L1蛋白阳性率显著高于癌旁对照组和肺良性对照组。不同组织类型原发灶中HPV L1蛋白检测阳性率存在明显差别,肺腺癌HPV L1蛋白检测阳性率显著高于肺鳞癌。109例NSCLC标本HPV16/18 L1基因序列11例阳性。HPV L1蛋白阳性肺腺癌患者KRAS基因突变率显著高于阴性,而EGFR、ALK、BRAF基因状态与HPV L1蛋白阳性无明显相关。结论 HPV感染与NSCLC发生可能有密切关系,尤其以肺腺癌关系更为密切;KRAS突变可能是HPV相关肺腺癌发病的驱动基因类型,为开展肺癌精准治疗指明方向。
[Abstract]:Objective to investigate the relationship between human papillomavirus (HPV) (HPV) infection and non-small cell lung cancer (NSCLC) (NSCLC), and to analyze the relationship between HPV infection and NSCLC clinicopathological features and multiple gene mutations. Methods the paraffin embedded tissue specimens of 264 cases of NSCLC and 65 cases of metastatic lesions were collected. Two hundred and sixty-four cases of adjacent epithelial tissue (paracancerous control group) and 12 cases of benign lung tissue were selected as control group. HPV L1 protein was detected by immunohistochemical En Vision method. The sequence of HPV16/18 L1 gene was detected by real-time fluorescence quantitative PCR (RTPCR) in 109 NSCLC samples, and the EGFR,ALK,KRAS,BRAF gene status RT-PCR method was used in 90 cases of lung adenocarcinoma. Results the positive rate of HPV L1 protein in primary NSCLC was similar to that in metastatic focus. The positive rate of HPV L1 protein in primary NSCLC was significantly higher than that in paracancerous control group and benign lung control group. The positive rate of HPV L1 protein was significantly different in different tissue types. The positive rate of HPV L1 protein in lung adenocarcinoma was significantly higher than that in lung squamous cell carcinoma. The mutation rate of KRAS gene in 109 NSCLC specimens was higher than that in lung squamous cell carcinoma. The mutation rate of KRAS gene was significantly higher in patients with HPV L1 protein positive lung adenocarcinoma than that in lung squamous cell carcinoma. There was no significant correlation between BRAF gene status and HPV L1 protein positive. Conclusion HPV infection may be closely related to the occurrence of NSCLC, especially lung adenocarcinoma, and KRAS mutation may be the driving gene type of HPV associated lung adenocarcinoma, which indicates the direction of accurate treatment for lung cancer.
【作者单位】：安徽医科大学附属省立医院呼吸内科;阜阳市第二人民医院结核科;安徽医科大学附属省立医院病理科;
【基金】：安徽省卫生厅医学科研基金(编号:13zc001) 安徽省科技厅攻关计划项目(编号:1301042216)
【分类号】：R734.2

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