解放军医学杂志2018，Vol.43Issue(3)：217-223,7.DOI:10.11855/j.issn.0577-7402.2018.03.07
PI3K/AKT信号通路与HER2阳性乳腺癌患者总生存时间的相关性及验证分析
Analysis and validation of PI3K/AKT signaling pathway associated with overall survival time of patients with HER2-positive breast cancer
摘要
Abstract
Objective To analyze and validate the key molecular targets correlated with the overall survival of patients with HER2-positive breast cancer.Methods First,the survival time and transcriptome data of patients with HER2-positive breast cancer in stage Ⅰ / Ⅱ and Ⅲ/Ⅳ were downloaded from the TCGA database.The significantly differential genes between overall survival ＜2 years and ＞8.5 years in stage Ⅰ / Ⅱ were picked out by edgeR package,and the pathways were enriched by KEGG.Similarly,the differential genes between overall survival ＜2 years and ＞7 years in stage Ⅲ/Ⅳ were analyzed.Furthermore,KEGG pathway analysis was performed using the differential genes overlapped by stage Ⅰ /Ⅱ and Ⅲ/Ⅳ.Second,the relationships between the expression levels of key node genes and other genes in enriched pathway and the overall survival of patients with HER2-positive breast cancer were validated by KMplot database.Last,the correlation between the activity of pathway enriched in KEGG and the resistance to anti-HER2 treatment was validated in HER2-positive breast cancer cell line BT474.Results In patients with stage Ⅰ / Ⅱ HER2-positive breast cancer whose overall survival was ＜2 years,PI3K/AKT was the 9th signaling pathway enriched by up-regulated differential genes.In patients with stage Ⅲ/Ⅳ whose overall survival was ＜2 years,PI3K/AKT was the 2nd signaling pathway enriched by up-regulated differential genes.Furthermore,PI3K/AKT was the first signal pathway enriched by the overlapping upregulated genes of patients in stage Ⅰ / Ⅱ and Ⅲ / Ⅳ whose overall survival was ＜2 years.Patients with high expression of PI3K and AKT (key node genes) or CFAP221 and COL4A6 (other genes) of PI3K/AKT pathway had shorter overall survival than those with low expression.PI3K inhibitors could enhance the growth inhibitory effect of HER2 small molecule inhibitor on HER2-positive breast cancer cell line BT474.Conclusions The overexpression of PI3K/AKT pathway is associated with the shorter overall survival in HER2-positive breast cancer patients,and associated with anti-HER2 resistance in HER2-positive breast cancer cell line.关键词
TCGA数据库/PI3K/AKT信号通路/HER2阳性乳腺癌Key words
TCGA database/PI3K/AKT signal pathway/HER2 positive breast cancer分类
医药卫生引用本文复制引用
李慧,钱海利,詹启敏,李春晓,南鹏,王婷,王劲松,张竞尧,窦娜,马飞,王海娟..PI3K/AKT信号通路与HER2阳性乳腺癌患者总生存时间的相关性及验证分析[J].解放军医学杂志,2018,43(3):217-223,7.基金项目
国家重点基础研究计划(973计划)(2015CB553904) （973计划）
国家自然科学基金(81372158、81372159、81572842、81672459) （81372158、81372159、81572842、81672459）
中国医学科学院医学与健康创新科技工程项目(2016-12M-1-001) （2016-12M-1-001）
分子肿瘤学国家重点实验室开放课题(SKL-KF-2017-16) （SKL-KF-2017-16）
分子肿瘤学国家重点实验室自主创新课题(SKL-2017-16)This work was supported by the National Basic Research Program of China (973 Program)(2015CB553904) （SKL-2017-16）
the National Natural Science Foundation of China (81372158,81372159,81572842,81672459) （81372158,81372159,81572842,81672459）
CAMS Innovation Fund for Medical Sciences (CIFMS)(2016-I2M-1-001) （CIFMS）
the Open Issue of State Key Laboratory of Molecular Oncology (SKL-KF-2017-16) and the Independent Issue of State Key Laboratory of Molecular Oncology (SKL-2017-16) （SKL-KF-2017-16）
