摘要
目的探讨结肠腺癌中DNA甲基化调控SLC35D1表达及与预后的关系。方法从癌症基因组图集(TCGA)数据库下载结肠腺癌的表达和甲基化数据,分析SLC35D1在结肠腺癌组织和正常组织的表达和甲基化情况,同时从基因表达数据库下载结肠腺癌的表达和甲基化数据进行验证。利用Kaplan-Meier方法分析SLC35D1对结肠腺癌患者预后的影响,构建患者列线图模型,对SLC35D1及共表达基因进行功能富集分析,分析SLC35D1表达与肿瘤浸润免疫细胞的关系,验证SLC35D1启动子甲基化转录沉默关系。结果SLC35D1在结肠腺癌组织中表达低于正常组织(P<0.01)。结肠腺癌组织中SLC35D1甲基化程度高于正常组织(P<0.01)。SLC35D1低表达患者的总生存率低于高表达患者(P<0.05)。联合SLC35D1表达、年龄和TNM分期构建的列线图模型能够高效地预测结肠腺癌患者的预后。SLC35D1表达水平改变与肿瘤免疫微环境相关。qRCP结果显示,在结直肠癌细胞SW480中SLC35D1低表达,经过DNA甲基化转移酶抑制剂处理后SLC35D1表达恢复(P<0.05)。结论在结肠腺癌中SLC35D1低表达受其甲基化调控,是患者不良预后标志物,其可能通过MAPK通路和影响肿瘤免疫微环境调控结肠腺癌的进展。
Objective To investigate SLC35D1 expression regulated by DNA methylation and its relationship with prognosis in patients with colon adenocarcinoma.Methods The expression and methylation data of colon adenocarcinoma were downloaded from The Cancer Genome Atlas(TCGA)database to analyze the expression and methylation of SLC35D1 in colon adenocarcinoma tissues and normal tissues,and the expression and methylation data of colon adenocarcinoma were downloaded from the comprehensive gene expression database for verification.The prognostic value of SLC35D1 in colon adenocarcinoma was analyzed by Kaplan-Meier method.The nomogram model of patients was constructed,and functional enrichment analysis of SLC35D1 and co-expressed genes was performed.The relationship between SLC35D1 expression and tumor-infiltrating immune cells was analyzed and the relationship between SLC35D1 promoter methylation and transcriptional silencing was verified.Results The expression of SLC35D1 in colon adenocarcinoma tissues was lower than that in normal tissues(P<0.01).The methylation of SLC35D1 in colon adenocarcinoma tissues was higher than that in normal tissues(P<0.01).The overall survival rate of patients with low SLC35D1 expression was lower than that with high SLC35D1 expression(P<0.05).The nomogram model constructed by the combination of SLC35D1 expression,age,and TNM staging could effectively predict the prognosis of patients with colon adenocarcinoma.The change of SLC35D1 expression level was related to tumor immune microenvironment.Quantitative PCR(qRCP)results showed that SLC35D1 expression was low in colon adenocarcinoma/colorectal cell SW480,and SLC35D1 expression was recovered after treatment with DNA methyltransferase inhibitors(P<0.05).Conclusion The low expression of SLC35D1 in colon adenocarcinoma is regulated by its methylation and is a marker of poor prognosis in patients.It may regulate the progression of colon adenocarcinoma through MAPK pathway and influence of the tumor immune microenvironment.
作者
徐冬梅
张佳佳
宋清玲
贾克然
XU Dongmei;ZHANG Jiajia;SONG Qingling;JIA Keran(Department of Laboratory Medicine,the 980th Hospital of the Joint Logistics Support Force of the PLA,Shijiazhuang 050082,China;Department of Laboratory Pathology,Lintong Rehabilitation Center,the Joint Logistics Support Force of the PLA,Xi'an 710600,China)
出处
《临床误诊误治》
CAS
2024年第18期44-52,共9页
Clinical Misdiagnosis & Mistherapy
基金
国家重点研发计划项目(2022YFF0710300)。
