Deng Zhao Min, Liu Lin, Qiu Wen Hai, Zhang Yong Qun, Zhong Hong Yan, Liao Ping, Wu Yun Hong
Hospital of Chengdu Office of People's Government of Tibetan Autonomous Region, Chengdu, China.
West China Second University Hospital, Chengdu, China.
PeerJ. 2017 May 10;5:e3216. doi: 10.7717/peerj.3216. eCollection 2017.
Molecularly targeted therapies improved survival status of some patients with lung adenocarcinoma, which accounts for 40% of all lung cancers, and in-depth study of gene alterations is important for the personalized treatment.
The legacy archive data of clinical information and genomic variations under the project TCGA Lung Adenocarcinoma were downloaded from the GDC Data Portal using R package TCGAbiolinks. The significantly aberrant copy number variants segments were figured out using GAIA. After annotation, the genes involving CNV were used to get enriched pathways. Recurrent amplifications and deletions were identified and visualized by OncoPrint. Genomic alterations in cancer, including CNV and mutations, were represented in Circos.
The significantly aberrant CNV segments were found, and the genes involved were associated with the immune system. In an analysis of 517 mutation annotated files, we highlighted 63 highly recurrent mutated genes which were associated with lung cancer signaling. These genes involved in important pathways related to cancer progression. The intersections between the genes involving in the significantly aberrant CNV and the genes harboring recurrent somatic SNP were extracted. The PI3K protein family acted as critical roles in the lung adenocarcinoma, since the components of the PI3K protein family include PIK3C2B, PIK3CA, PIK3R1 and so forth were presented in the intersections.
We represented a comprehensive annotation of genomic alterations in lung adenocarcinoma and proposed that PI3K signaling proteins were critical for it.
分子靶向治疗改善了部分肺腺癌患者的生存状况，肺腺癌占所有肺癌的40%，深入研究基因改变对个性化治疗很重要。
使用R包TCGAbiolinks从GDC数据门户下载TCGA肺腺癌项目下的临床信息和基因组变异的遗留存档数据。使用GAIA找出显著异常的拷贝数变异片段。注释后，使用涉及CNV的基因来获得富集通路。通过OncoPrint识别并可视化复发性扩增和缺失。癌症中的基因组改变，包括CNV和突变，在Circos中展示。
发现了显著异常的CNV片段，涉及的基因与免疫系统相关。在对517个突变注释文件的分析中，我们突出了63个高度复发性突变基因，这些基因与肺癌信号传导相关。这些基因参与了与癌症进展相关的重要通路。提取了涉及显著异常CNV的基因与携带复发性体细胞SNP的基因之间的交集。PI3K蛋白家族在肺腺癌中起关键作用，因为PI3K蛋白家族的组成部分包括PIK3C2B、PIK3CA、PIK3R1等都出现在交集中。
我们展示了肺腺癌基因组改变的全面注释，并提出PI3K信号蛋白对其至关重要。
