中国临床医学2018，Vol.25Issue(2)：210-216,7.DOI:10.12025/j.issn.1008-6358.2018.20180016
早期乳腺癌患者循环肿瘤细胞TP53、磷脂酰肌醇-3激酶基因突变分析及其与患者临床病理特征的相关性
Analysis of TP53 and PI3K gene mutations in circulating tumor cells in patients with early breast cancer and their correlation with clinical pathological features
摘要
Abstract
Objective:To investigate the count of circulating tumor cells(CTC)as well as the mutation of TP53 and PI3K gene in patients with early breast cancer, and to analyze the relationship between the gene mutation and clinicopathological features.Methods:A total of 30 patients diagnosed with breast cancer and benign breast masses were collected during January to February 2015.CellSearch method was used to detect CTCs in blood.The mutations of TP53 (p.R248Q,p.R273H,p.R175H)and PI3K(p.E545K,p.H1047R)in patients' blood,CTC,and urine were detected by droplet digital PCR techniques(ddPCR).Meanwhile,the clinical data of all patients were collected including age of onset, tumor size,histological grade,molecular typing,axillary lymph node status,and Ki-67.The relationship between the mutations and clinicopathological features was analyzed.Results:A total of 82(18.9%)were found positive mutations in 435 samples from 29 patients with blood,CTC,and urine samples.The mutation rate of each gene was different,the highest was TP53(p.R175H)with 29 samples(6.7%),the lowest was PI3K(p.E545K)having only 1 sample(0.2%).The mutation rates of five genes were statistically different(χ2 = 50.133,P< 0.001).There were significant differences in the mutation rates among five genes of CTC,blood,and urine(likelihood ratio = 14.204,P= 0.007;χ2 = 25.172,P< 0.001;χ2 =16.681,P=0.002).The highest mutation rate was TP53(p.R175H)in the three types of specimens.There was a correlation between TP53 gene mutation and the clinicopathological features of some patients with breast cancer.The molecular type of breast cancer and the degree of Ki-67 were correlated with the mutation of TP53(p.R248Q)in CTC specimen(Fisher's Exact Test = 10.839,P=0.003;P=0.028).The axillary lymph node metastasis was related to the mutation of TP 53(p.R175H) gene in CTC specimens(P=0.058).Conclusions:The molecular classification of breast cancer and the degree of tumor marker Ki-67 are associated with TP53(p.R248Q)mutation in CTC specimens from patients with early breast cancer.Axillary lymph node metastasis may also be associated with TP53(p.R175H)mutation in CTC specimens.It is suggested that the mutation of TP53 gene in CTC specimens may be a potential indicator for the selection of treatment regimen and prognosis of early breast cancer.关键词
乳腺肿瘤/肿瘤细胞,循环/DNA突变分析/TP53/磷脂酰肌醇-3激酶/尿液检查Key words
breast neoplasms/neoplastic cells/circulating/DNA mutational analysis/TP53/PI3K/uronoscopy分类
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林健,贾淞淋,方敏,吴雅妮,刘超乾,苏东玮,于跃,李恒宇,盛湲..早期乳腺癌患者循环肿瘤细胞TP53、磷脂酰肌醇-3激酶基因突变分析及其与患者临床病理特征的相关性[J].中国临床医学,2018,25(2):210-216,7.基金项目
国家自然科学基金青年项目(81502546),第二军医大学精准医学转化应用研究专项(2017JZ37,2017JZ07).Supported by Youth Project of National Natural Science Foundation of China(81502546)and the Special Research Program of Precision Medicine Transformation and Application by Second Military Medical University(2017JZ37,2017JZ07). （81502546）
