摘要
目的探索单独针对直肠乙状结肠交界处癌(RSC)的危险因素和生物标志物来预测患者预后并开发新的治疗靶点。方法本研究从肿瘤基因组图谱(TCGA)数据库中收集66例肿瘤和6例正常组织,使用PERL和R软件包综合分析23个m6A调控因子的表达水平、突变情况及与RSC患者预后的关系,通过确定了lncRNAs和m6A的关系,进一步利用Lasso回归构建预后模型。结果与邻近正常组织比较,23个m6A调节因子中有7个在RSC中存在差异表达,并且有5个m6A调节因子与患者预后相关(P<0.05)。共表达分析结果显示,278个lncRNA的表达与m6A密切相关,许多lncRNAs是预测RSC预后的危险因素(P<0.05)。m6A-lncRNAs在肿瘤组织中表达异常(P<0.05),可用于预测RSC预后的模型,不受其他临床特征影响。通过LASSO回归,基于3个m6A-lncRNAs分子MCM3AP-AS1、AF117829.1和HCG15建立RSC的预后模型,生存曲线证明了该模型在预测患者生存率方面具有较高的准确性(P<0.05),该模型可以应用于不同临床分层亚组的预后判断。结论m6A甲基化修饰异常及m6A相关lncRNAs与RSC的发生密切相关,相应的预后模型可以为RSC患者的预后评估和个性化治疗策略提供依据。
Objective The rectosigmoid junction is the most common site of colon cancer.This study aims to explore the risk factors and biomarkers of rectosigmoid junction cancer(RSC)to predict the prognosis of patients and develop new therapeutic targets.Methods A total of 66 tumors and 6 normal tissues were collected from the the cancer genome atlas(TCGA)database.The expression level and mutation of 23 m6A regulatory factors and their relationship with the prognosis of RSC patients were comprehensively analyzed using PERL and R software packages.By determining the relationship between lncRNAs and m6A,the prognosis model was further constructed using Lasso regression.Results Compared with adjacent normal tissues,7 of 23 m6A regulatory factors were differentially expressed in RSC,and 5 m6A regulatory factors were correlated with patient’s prognosis(P<0.05).Co-expression analysis showed that the expression of 278 lncRNAs was closely related to m6A,and many lncRNAs were risk factors for predicting RSC prognosis(P<0.05).The abnormal expression of m6A-lncRNAs in tumor tissue(P<0.05)could be used as a model to predict the prognosis of RSC,which was not affected by other clinical features.Through LASSO regression,a prognosis model of RSC was established based on 3 m6A-lncRNAs(MCM3AP-AS1,AF117829.1,and HCG15).The ROC curve proved that the model had high accuracy in predicting the survival rate of patients(P<0.05),and the clinical data of patients confirmed that the model could be used to predict the prognosis of different clinical stratification subgroups.Conclusion The results show that the abnormal methylation modification of m6A and m6A related lncRNAs are closely related to the occurrence of RSC.The corresponding prognosis model can provide a new idea for the prognosis evaluation and personalized treatment strategy of RSC patients.
作者
周威
李倩
李彩茹
曹灵
程智慧
陈晨
洪流
Zhou Wei;Li Qian;Li Cairu;Cao Ling;Cheng Zhihui;Chen Chen;Hong Liu(Department of Digestive Surgery,Digestive Hospital of the First Affiliated Hospital,Air Force Medical University,Xi’an 710032,China)
出处
《中华实验外科杂志》
CAS
北大核心
2023年第3期443-446,共4页
Chinese Journal of Experimental Surgery
基金
国家自然科学基金面上项目(82073210)。
