基于GSCA数据库分析ctDNA在乳腺癌患者中的应用价值

Analysis on Application Value of ctDNA in Breast Cancer Patients Based on GSCA Database

目的探讨循环肿瘤DNA(ctDNA)在乳腺癌患者中的应用价值。方法选取2018年1月至2020年1月陆军军医大学大坪医院确诊的31例浸润性乳腺癌患者为研究对象,提取患者术前血液样本、肿瘤组织样本、术后6个月血液样本的ctDNA样本,选取前20个高频突变基因制备基因集。利用GSCA数据库分析基因集蛋白表达水平与乳腺癌患者生存期的关系,比较不同分子分型的基因表达差异,分析基因集表达与免疫细胞浸润和药物敏感性的关系。结果31例患者共检测了87份样本,最常见的突变基因是赖氨酸甲基转移酶2C(KMT2C)(20.69%)、磷脂酰肌醇-3-激酶催化亚单位α(PIK3CA)(18.39%)和肿瘤蛋白53(18.39%);20个基因高低表达结果显示,PIK3CA、核受体结合SET域蛋白1、KMT2C、赖氨酸乙酰转移酶6A(KAT6A)、胰岛素受体底物2(IRS2)与患者无进展生存期相关(P<0.05),KAT6A和IRS2与患者总生存期相关(P<0.05);血小板衍生生长因子受体、间变性淋巴瘤激酶、RecQ样解旋酶4、含F-框WD重复域蛋白7与免疫细胞呈显著正相关;基因集错义突变数目最多,变体类型主要为单核苷酸变异;酪氨酸激酶受体2、IRS2和脂肪非典型钙黏蛋白-1的药物敏感性最显著。结论ctDNA在乳腺癌组织和血液样本中检测结果高度一致,特定变异基因可用于监测复发和解决耐药,ctDNA对评估乳腺癌预后和寻找靶向药物具有一定价值。

Objective To explore the application value of circulating tumor DNA(ctDNA)in breast cancer patients.Methods A total of 31 patients with invasive carcinoma of the breast diagnosed in Daping Hospital of Army Military Medical University from Jan.2018 to Jan.2020 were included.Their ctDNA samples were collected from preoperative blood samples,tumor tissue samples and blood samples 6 months after surgery,and the top 20 high-frequency mutant genes were selected to prepare a gene set.The gene set cancer analysis(GSCA)database was used to analyze the relationship between gene set protein expression level and breast cancer survival,compare gene expression differences of different molecular types,and analyze the correlation of gene set expression with immune cell infiltration and drug sensitivity.Results A total of 87 samples of the 31 patients were tested.The most common mutant genes were lysine methyltransferase 2C(KMT2C)(20.69%),phosphatidylinositol 3-kinase catalyticαpolypeptide(PIK3CA)(18.39%)and tumor protein p53(18.39%);the high and low expression results of 20 genes showed that PIK3CA,nuclear receptor binding SET domain protein 1,KMT2C,lysine acetyltransferase 6A(KAT6A)and insulin receptor substrate 2(IRS2)were related to the patient′s progression free survival(P<0.05),KAT6A and IRS2 were related to the patient′s over survival(P<0.05);platelet-derived growth factor receptor,anaplastic lymphoma kinase,RecQ-like helicase 4,F-box and WD-repeat-domain-containing 7 were significantly positively correlated with immune cells;the number of missense mutations in the gene set was the most,and the variant type was mainly single-nucleotide variation;tyrosine kinase receptor 2,IRS2 and FAT atypical cadherin 1 were the genes with the most significant drug susceptibility.Conclusion The detection results of ctDNA in breast cancer tissues and blood samples are highly consistent.Specific variant genes can be used to monitor the recurrence and resolve the drug resistance,and ctDNA has certain value in assessing the prognosis of breast cancer and the search for targeted drugs.