Characterization of AKT Somatic Mutations in Chinese Breast Cancer Patients.
Characterization of AKT Somatic Mutations in Chinese Breast Cancer Patients.
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DOI：
10.2147/cmar.s299624
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发表时间：
2021
影响因子：
3.3
通讯作者：
Liao N
中科院分区：
文献类型：
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作者：
Wen L;Zhang G;Ren C;Li X;Mok H;Jia M;Wang Y;Chen B;Li K;Cao L;Li C;Xiao W;Lai J;Lin J;Wei G;Li Y;Zhang Y;Chen X;Liao N
本研究旨在探讨AKT基因在中国乳腺癌患者中的突变状况。该研究纳入了2017年6月1日至2018年9月27日在广东省人民医院住院的411例乳腺癌患者。进行乳房切除术或保乳手术，并对组织样本进行下一代测序（NGS）以确定AKT基因突变状态。同时免疫组化染色分析人表皮生长因子受体2 （Her2）、孕激素受体（PR）、雌激素受体（ER）的表达。使用癌症基因组图谱（TCGA）数据库进行比较研究。GDPH组患者年龄较大（P < 0.001），绝经后发生率较高（P < 0.001），肿瘤大小较大（P < 0.001），浸润性导管癌组织学类型较高（P < 0.001），转移率较高（P < 0.001）， ER （P = 0.015）和HER2表达较高（P < 0.001）， HR/HER2亚型比例高于TCGA组（P < 0.001）。与TCGA组相比，GDPH组总体AKT和AKT3突变率较低（P < 0.001），但AKT1突变率较高（P < 0.0001）。值得注意的是，NGS研究分别发现错义突变和拷贝数扩增是GDPH和TCGA队列中最常见的AKT变异类型。其中，在GDPH组中主要检测到AKT1中的E17K突变，而在TCGA组中不存在。此外，在GDPH队列中，AKT变异与许多临床病理变量相关，包括年龄超过50岁、HER2-、HR+/HER2-和PR+。GDPH组患者的AKT和AKT3突变率低于TCGA组，AKT1突变率高于TCGA组，同时存在以AKT1中E17K突变为主的错义突变。在GDPH队列中，AKT突变与患者的临床病理特征存在相关性。
This study aimed to investigate AKT gene mutation status in Chinese breast cancer patients. The study included 411 breast cancer patients hospitalized in Guangdong Provincial People’s Hospital (GDPH) from June 1, 2017 to September 27, 2018. Mastectomy or breast conserving surgery was performed, and tissue samples were subjected to next-generation sequencing (NGS) to determine AKT gene mutation status. Meanwhile, the expression of human epidermal growth factor receptor 2 (Her2), progesterone receptor (PR), and estrogen receptor (ER) was analyzed by immunohistochemistry staining. The Cancer Genome Atlas (TCGA) database was used for comparative studies. Patients in the GDPH cohort had an older age (P < 0.001), higher postmenopausal rate (P < 0.001), larger tumor size (P < 0.001), higher histologic type of infiltrating duct cancer (P < 0.001), higher metastatic rate (P < 0.001), higher expression of ER (P = 0.015) and HER2 (P < 0.001), and higher percentage of the HR/HER2 subtype (P < 0.001) than those in the TCGA cohort. The GDPH cohort displayed lower rates of overall AKT and AKT3 mutation (P < 0.001), but a higher AKT1 mutation rate (P < 0.0001) compared with the TCGA cohort. Notably, the NGS studies identified missense mutation and copy number amplification as the most common AKT variation type in the GDPH and TCGA cohorts, respectively. Specifically, E17K mutation in AKT1 was predominantly detected in GDPH cohort, while being absent in TCGA cohort. Moreover, in the GDPH cohort, AKT variation was correlated with a number of clinicopathological variables, including age over 50, HER2-, HR+/HER2-, and PR+. Patients in the GDPH cohort had lower rates of AKT and AKT3 mutation and higher AKT1 mutation rate than those in the TCGA cohort, while harboring missense mutations detected predominantly as E17K mutation in AKT1. In GDPH cohort, there were correlations between AKT mutation and the clinicopathological characteristics of patients.