乳腺癌PIK3CA基因突变特征分析  

Characteristic PIK3CA gene mutation in breast cancer

作　　者：赵佳宁 张会蕊 刘月平[1] Zhao Jianing;Zhang Huirui;Liu Yueping(Department of Pathology,the Fourth Hospital of Hebei Medical University,Shijiazhuang 050011,China)

机构地区：[1]河北医科大学第四医院病理科,石家庄050011

出　　处：《中华病理学杂志》2025年第3期243-249,共7页Chinese Journal of Pathology

基　　金：河北省自然科学基金(H2024206504)。

摘　　要：目的探讨乳腺癌中PIK3CA基因突变图谱,为乳腺癌PIK3CA抑制剂的精准治疗提供新的研究依据。方法回顾性分析河北医科大学第四医院2015—2020年乳腺癌患者的肿瘤活检样本,在接受新辅助治疗前采集的样本共涉及144例。通过二代测序技术检测了520个与实体瘤发生、发展及靶向治疗密切相关的基因,重点分析了PIK3CA基因的突变情况。进一步对患者的发病年龄、分子分型及Ki-67等临床病理特征进行分析,并采用Pearson卡方检验和Mann Whitney检验评估PIK3CA基因突变与这些临床病理特征之间的相关性。与此同时,通过Logistic回归模型进行多因素分析,以探讨影响PIK3CA基因突变的潜在因素。最后,使用R语言包进行了Kaplan-Meier生存分析,并构建Cox比例风险回归模型,以评估相关因素对患者生存率的影响。结果在144例乳腺癌样本中,共检测到61例(42.3%,61/144)存在PIK3CA基因突变。具体而言,HER2过表达型乳腺癌中有23例(53.5%,23/43)检出PIK3CA突变,Luminal型乳腺癌中有28例(44.4%,28/63),而三阴性乳腺癌中则有10例(27.8%,10/36)出现该基因突变。在这些突变位点中,3个PIK3CA热点突变占据了突变总数的72.1%,其中H1047R(52.4%)、E545K(16.4%)、E542K(3.3%)为主要突变类型,其余罕见突变占比27.87%。此外,本研究队列中还观察到PIK3CA与其他基因的共突变现象,PIK3CA与TOP2A、FOXA1为共现基因对,而与GATA3、BRCA2为互斥基因对。分析结果显示,PIK3CA基因的突变状态与HER2状态显著相关,与患者的年龄、绝经状态、激素受体状态、Ki-67阳性指数、分子分型、TNM分期及病理完全缓解状态均无显著相关性,并且不同的PIK3CA突变状态与总生存率之间未发现显著关联。结论本研究队列明确了PIK3CA基因在乳腺癌中的总体突变率及各分子亚型的突变频率,并揭示了PIK3CA突变与HER2状态的显著相关性,为乳腺癌PIK3CA抑制剂的精准治疗提供了新的研ObjectiveTo investigate the mutation spectrum of the PIK3CA gene in breast cancer,providing a new basis for the precise treatment of breast cancer with PIK3CA inhibitors.MethodsA retrospective analysis was conducted on 144 breast cancer patients who underwent biopsy before neoadjuvant therapy archived from 2015 to 2020 at the Fourth Hospital of Hebei Medical University.Next-generation sequencing(NGS)was utilized to detect the mutations of 520 genes closely related to the development of solid tumors and targeted therapies.The study compared the differences between reported mutation types and focused on analyzing the mutation status of the PIK3CA gene.The clinical and pathological characteristics,including age of onset,molecular subtypes,and Ki-67,were also analyzed.The correlation between PIK3CA mutations and clinicopathological characteristics was examined using Pearson×s chi-square test and Mann Whitney test.Logistic regression was employed to analyze factors influencing PIK3CA mutations.Kaplan-Meier survival analysis and Cox regression models were constructed using R programming.ResultsAmong the 144 breast cancer samples,61(42.3%,61/144)exhibited PIK3CA gene mutations,of which 23 cases(53.5%,23/43)were HER2-positive breast cancer,28 cases(44.4%,28/63)were luminal breast cancer,and 10 cases(27.8%,10/36)were triple-negative breast cancer.Of the detected mutations,three hotspot mutations(H1047R,E545K,and E542K)accounted for 72.1%of the total PIK3CA mutations,with H1047R(52.4%),E545K(16.4%),and E542K(3.3%)most commonly detected.The remaining rare mutations accounted for 26.3%.Co-mutations involving PIK3CA and other genes were also observed in the cohort,occurring with TOP2A and FOXA1,while being mutually exclusive with GATA3 and BRCA2.PIK3CA mutations were significantly associated with HER2 status and were not significantly correlated with the patient′s age,menopausal status,HR status,Ki-67 index,molecular typing,TNM stage or pCR status.Likewise,no significant correlation was found between different PIK3CA mutat

关 键 词：乳腺肿瘤 基因 突变 PIK3CA 

分 类 号：R73[医药卫生—肿瘤]