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PI3K/AKT信号通路中的基因变异与接受放射治疗的肺癌患者严重放射性肺炎相关。

Genetic variants in PI3K/AKT pathway are associated with severe radiation pneumonitis in lung cancer patients treated with radiation therapy.

作者信息

Tang Yang, Liu Bo, Li Jing, Wu Huanlei, Yang Ju, Zhou Xiao, Yi Mingxiao, Li Qianxia, Yu Shiying, Yuan Xianglin

机构信息

Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.

出版信息

Cancer Med. 2016 Jan;5(1):24-32. doi: 10.1002/cam4.564. Epub 2015 Dec 8.

DOI:10.1002/cam4.564
PMID:26645682
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4708901/
Abstract

PI3K/AKT pathway plays important roles in inflammatory and fibrotic diseases while its connection to radiation pneumonitis (RP) is unclear. In this study, we explored the associations of genetic variants in PI3K/AKT pathway with RP in lung cancer patients with radiotherapy. Two hundred and sixty one lung cancer patients with radiotherapy were included in this prospective study (NCT02490319) and genotyped by MassArray and Sanger Sequence methods. By multivariate Cox hazard analysis and multiple testing, GA/GG genotype of AKT2: rs33933140 (HR = 0.272, 95% CI: 0.140-0.530, P = 1.3E-4, Pc = 9.1E-4), and the GT/GG genotype of PI3CA: rs9838117 (HR = 0.132, 95% CI: 0.042-0.416, P = 0.001, Pc = 0.006) were found to be strongly associated with a decreased occurrence of RP ≥ grade 3. And patients with the CT/TT genotype of AKT2: rs11880261 had a notably higher incidence of RP ≥ grade 3 (HR = 2.950, 95% CI: 1.380-6.305, P = 0.005, Pc = 0.025). We concluded that the genetic variants of PI3K/AKT pathway were significantly related to RP of grade ≥ 3 and may thus be predictors of severe RP before radiotherapy, if further validated in larger population.

摘要

PI3K/AKT通路在炎症性疾病和纤维化疾病中发挥着重要作用，但其与放射性肺炎（RP）的关系尚不清楚。在本研究中，我们探讨了PI3K/AKT通路中的基因变异与接受放疗的肺癌患者发生RP之间的关联。本前瞻性研究（NCT02490319）纳入了261例接受放疗的肺癌患者，并采用MassArray和Sanger测序方法进行基因分型。通过多变量Cox风险分析和多重检验，发现AKT2的GA/GG基因型：rs33933140（HR = 0.272，95%CI：0.140 - 0.530，P = 1.3E - 4，Pc = 9.1E - 4），以及PI3CA的GT/GG基因型：rs9838117（HR = 0.132，95%CI：0.042 - 0.416，P = 0.001，Pc = 0.006）与≥3级RP发生率降低密切相关。而AKT2的CT/TT基因型：rs11880261的患者≥3级RP的发生率显著更高（HR = 2.950，95%CI：1.380 - 6.305，P = 0.005，Pc = 0.025）。我们得出结论，如果在更大规模人群中进一步验证，PI3K/AKT通路的基因变异与≥3级RP显著相关，因此可能是放疗前严重RP的预测指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01e2/4708901/b230b6c36612/CAM4-5-024-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01e2/4708901/977a1f27a977/CAM4-5-024-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01e2/4708901/44ba30a39fff/CAM4-5-024-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01e2/4708901/b230b6c36612/CAM4-5-024-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01e2/4708901/977a1f27a977/CAM4-5-024-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01e2/4708901/44ba30a39fff/CAM4-5-024-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01e2/4708901/b230b6c36612/CAM4-5-024-g003.jpg

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