摘要
目的通过生物信息学的方法,构建并验证预测雌激素受体阳性乳腺癌他莫昔芬治疗预后的长链非编码RNA(lncRNA)模型。方法利用基因表达综合(GEO)数据库提取雌激素受体阳性乳腺癌芯片测序数据,并从中下载他莫昔芬耐药及敏感细胞系的lncRNA表达数据集,通过单因素和多因素Cox回归分析构建预后模型。根据模型计算风险比(HR),分析高危组、低危组的临床病理参数与预后的关系,并用验证集样本对训练集的结果进行验证。结果在GEO数据库和癌症基因组图谱(TCGA)数据库对他莫昔芬敏感与他莫昔芬耐药乳腺癌患者的差异lncRNA进行比对筛选,最终获得116个差异lncRNA。对差异lncRNA进行单因素Cox回归分析,计算每个lncRNA与乳腺癌患者总生存率的HR及P值,最终得到8个相关的lncRNA(P<0.05)。通过多因素Cox回归分析最终建立由6个lncRNA组成的预后模型。按照训练集中HR的中位数将训练集及验证集中的患者分为高危组、低危组,Log-rank检验结果发现,高危组与低危组在训练集和验证集中的生存率差异均有统计学意义(P=7×10^(-7)、0.008)。结论乳腺癌他莫昔芬耐药相关预后模型6个lncRNA对雌激素受体阳性乳腺癌患者预后具有一定价值,可为逆转他莫昔芬耐药、治疗癌症的研究提供依据。
Objective To construct and verify a long non-coding RNA(lncRNA)model for predicting the prognosis of estrogen receptor positive breast cancer treated with tamoxifen by bioinformatics method.Methods Gene Expression Omnibus(GEO)database was used to extract the chip sequencing data of estrogen receptor positive breast cancer,from which lncRNA expression data sets of tamoxifen-resistant and sensitive cell lines were downloaded.The prognostic models were constructed by univariate and multivariate Cox regression analysis.Hazard ratio(HR)was calculated according to the model,and the relationship between clinicopathological parameters and prognosis was analyzed in high-risk group and low-risk group.The relevant data sets in the cancer genome atlas database were randomly divided into training set and validation set,and the results of training set samples were verified by validation set.Results Differential lncRNAs of tamoxifen-sensitive and tamoxifen-resistant breast cancer patients were compared and screened in GEO database and the cancer genome atlas(TCGA)database,and finally 116 lncRNAs were obtained.Subsequently,univariate Cox regression analysis was performed to calculate the HR and P values of each lncRNA and the overall survival rate of breast cancer patients,and finally 8 significantly related lncRNAs were obtained(P<0.05).Multivariate Cox regression analysis was used to establish a prognostic model consisting of 6 lncRNAs.According to the median HR in the training set,patients in the training set and validation set were divided into high-risk group and low-risk group.Log-rank test results showed that there were statistically significant differences in the survival rates of high-risk group and the low-risk group in the training set and validation set(P=7×10^(-7),0.008).Conclusion The 6 lncRNAs have certain prognostic value in patients with estrogen receptor positive breast cancer,which might provide a basis for the research of reversing tamoxifen resistance and treating cancer.
作者
郑洁
开震天
夏超然
罗鹏
刘晖
王建东
王凤
胡俊艳
ZHENG Jie;KAI Zhentian;XIA Chaoran;LUO Peng;LIU Hui;WANG Jiandong;WANG Feng;HU Junyan(Department of Breast Surgery,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Shanghai Topgen Biomedical Technology Co.,Ltd,Shanghai 201321,China)
出处
《检验医学与临床》
CAS
2022年第23期3227-3230,共4页
Laboratory Medicine and Clinic
关键词
乳腺癌
雌激素受体
他莫昔芬耐药
预后模型
breast cancer
estrogen receptor
tamoxifen-resistant
prognostic model
