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[煤尘肺及p16(ink4a)基因异常甲基化对小肺腺癌发生发展的影响。]

[The influence of anthracosis and p16(ink4a) gene abberant methylation to the oncogenesis and progression of small pulmonary adenocarcinoma.].

作者信息

Wang Daye, Wang Jue, Li Yong

机构信息

Clinicopathologic Center, Capital Medical University, Beijing 100069, China.

出版信息

Zhongguo Fei Ai Za Zhi. 2008 Aug 20;11(4):542-6. doi: 10.3779/j.issn.1009-3419.2008.04.006.

DOI:10.3779/j.issn.1009-3419.2008.04.006
PMID:20735966
Abstract

BACKGROUND

Anthracosis is black dust matter deposition in the pulmonary parenchyma, which can cause bronchial deformity and destruction. Previously reported, anthracosis is closely correlated to the oncogenesis and progression of small pulmonary adenocarcinoma and p16(ink4a) gene aberrant methylation was closely associated with lung carcinogenesis. In this study, we want to characterize the influence of anthracosis and p16(ink4a) gene aberrant methylation on small adenocarcinoma.

METHODS

DNA was bisulfite modified and then Methylation Specific PCR was used to detect p16(ink4a) gene aberrant methylation, and black dust matter was extracted from lung tissues, the absolute absorbance (A) detected by densitometry was defined as anthracotic index (AI). The histopathologic diagnosis was according to Noguchi's classification for small pulmonary adenocarcinoma.

RESULTS

For heavy smokers, the mean AI was significantly higher than that of nonsmokers (P =0.005) and the frequency of p16(ink4a) gene aberrant methylation was also significantly higher than that of nonsmokers (P =0.023). The frequency of p16(ink4a) gene aberrant methylation of early stage small adenocarcinoma was lower than that of advanced and poor differentiated small adenocarcinoma, otherwise p16(ink4a) protein expression of early stage small adenocarcinoma was significantly higher than that of poor differentiated small adenocarcinoma (P =0.032).

CONCLUSIONS

AI and p16(ink4a) gene aberrant methylation detection could be used as a combined potential biomarker of small adenocarcinoma.

摘要

背景

肺尘埃沉着病是黑色尘埃物质在肺实质中的沉积,可导致支气管畸形和破坏。先前报道,肺尘埃沉着病与小肺腺癌的发生和进展密切相关,且p16(ink4a)基因异常甲基化与肺癌发生密切相关。在本研究中,我们旨在探讨肺尘埃沉着病和p16(ink4a)基因异常甲基化对小腺癌的影响。

方法

对DNA进行亚硫酸氢盐修饰,然后采用甲基化特异性PCR检测p16(ink4a)基因异常甲基化,并从肺组织中提取黑色尘埃物质,通过密度测定法检测的绝对吸光度(A)定义为肺尘埃沉着病指数(AI)。组织病理学诊断根据Noguchi对小肺腺癌的分类。

结果

对于重度吸烟者,平均AI显著高于非吸烟者(P =0.005),p16(ink4a)基因异常甲基化频率也显著高于非吸烟者(P =0.023)。早期小腺癌p16(ink4a)基因异常甲基化频率低于晚期和低分化小腺癌,而早期小腺癌p16(ink4a)蛋白表达显著高于低分化小腺癌(P =0.032)。

结论

AI和p16(ink4a)基因异常甲基化检测可作为小腺癌联合潜在生物标志物。

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