机构地区:[1]内蒙古科技大学包头医学院中心临床学院,内蒙古包头014000 [2]包头市中心医院妇产科,内蒙古包头014000 [3]内蒙古医科大学包头临床医学院,内蒙古包头0140000
出 处:《癌症进展》2024年第7期762-770,共9页Oncology Progress
摘 要:目的研究N6-甲基腺嘌呤(m6A)相关长链非编码RNA(lncRNA)对卵巢癌预后的预测价值及免疫功能分析。方法通过癌症基因组图谱(TCGA)数据库获取卵巢癌患者转录组数据及临床数据,采用相关性分析筛选出与m6A共表达的lncRNA。通过Cox回归分析、最小绝对收缩和选择算子(LASSO)分析及随机森林模型确定构建预后风险评估模型的m6A相关lncRNA,利用受试者工作特征(ROC)曲线、Kaplan-Meier生存曲线、主成分分析(PCA)、Cox回归分析、列线图验证模型的预后价值及独立性。采用免疫相关性分析探究模型与免疫治疗的关系。采用实时定量聚合酶链反应验证卵巢癌细胞中m6A相关lncRNA的表达。结果共得到4个m6A相关lncRNA(AL138820.1、AC019080.1、AC007637.1、RFX3-AS1),其中,AL138820.1、AC007637.1高表达是卵巢癌患者预后的危险因素(HR﹥1),而RFX3-AS1高表达是卵巢癌患者预后的保护因素(HR﹤1)。卵巢癌患者预后影响因素分析结果显示,风险评分、年龄及肿瘤分期均为卵巢癌患者预后的独立影响因素(P﹤0.05)。构建列线图用于预测卵巢癌患者1、3、5年总生存率,该列线图的校准曲线在实际观测值和预测值之间表现出很高的准确性。实时定量逆转录聚合酶链反应结果显示,与人正常卵巢细胞株IOSE80比较,卵巢癌细胞系SKOV3中AL138820.1、AC019080.1、AC007637.1表达升高,RFX3-AS1表达降低,差异均有统计学意义(P﹤0.05)。结论本研究确定了卵巢癌中4个m6A相关lncRNA并构建了验证稳健的风险模型。该模型具有一定预测预后及免疫功能的价值,为基于m6A的卵巢癌早期诊断及治疗提供新的思路。Objective To investigate the predictive value of prognosis and immune function analysis of N6-methyladenosine(m6A)-related long non-coding RNA(lncRNA)in ovarian cancer.Method The transcriptomic data and clinical data of ovarian cancer patients were obtained through The Cancer Genome Atlas(TCGA)database,and the lncRNA co-expressed with m6A were selected by correlation analysis.Cox regression analysis,least absolute shrinkage and selection operator(LASSO)analysis and random forest model were used to determine the m6A-related lncRNA for constructing prognostic risk assessment model.The prognostic value and independence of the model were verified by receiver operating characteristic(ROC)curve,Kaplan-Meier survival curve,principal component analysis(PCA),Cox regression analysis,and nomogram.Immunocorrelation analysis was used to explore the relationship between the model and immunotherapy.Real-time quantitative polymerase chain reaction was used to verify the expression of m6A-related lncRNA in ovarian cancer cells.Result Four m6A-related lncRNA(AL138820.1,AC019080.1,AC007637.1,RFX3-AS1)were obtained.Among them,high expressions of AL138820.1 and AC007637.1 were risk factors for prognosis of ovarian cancer patients(HR>1).High expression of RFX3-AS1 was protective factor for the prognosis of ovarian cancer patients(HR<1).The results of prognostic factors of ovarian cancer patients showed that risk score,age and tumor stage were independent influencing factors for prognostic of ovarian cancer patients(P<0.05).The nomogram was constructed to predict 1-,3-,and 5-year overall survival for patients with ovarian cancer,the calibration curve showed high accuracy between actual observed and predicted value.Real-time quantitative reverse transcription polymerase chain reaction results showed that compared with human normal ovarian cell line IOSE80,the expressions of AL138820.1,AC019080.1 and AC007637.1 in SKOV3 ovarian cancer cell line were increased,while the expression of RFX3-AS1 was decreased,the differences were statistical
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