首页|铜死亡相关基因甲基化对宫颈癌预后的影响

铜死亡相关基因甲基化对宫颈癌预后的影响

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目的 探讨宫颈癌组织铜死亡相关基因的甲基化水平差异及对临床预后的影响.方法 从公共数据库中获取310份宫颈组织标本的甲基化数据,通过UALCAN数据库对12个铜死亡相关基因进行甲基化水平差异分析,研究其在宫颈癌不同分期和分级中的差异,从中筛选差异有统计学意义的基因,并通过EWAS datahub数据库进行预后分析.最后,对筛选出的基因进行基因富集分析、通路分析、免疫浸润分析,并使用cBioportal数据库分析该基因在宫颈癌中的突变率和肿瘤突变负荷(TMB).对甲基化水平和免疫细胞浸润差异采用两独立样本秩和检验;采用KM生存曲线和Log-rank双侧检验对总生存期进行比较分析;在TMB分析中使用Wilcoxon Test进行统计学分析;在GSEA和通路分析中使用皮尔逊相关分析.结果 患者宫颈癌组织中的细胞周期依赖激酶抑制基因2A(CDKN2A基因)甲基化β值为0.075,高于正常人组织中的甲基化β值0.049(P=0.008),患者宫颈癌组织中的二氢脂酰胺S-乙酰基转移酶(DLAT基因)甲基化β值为0.102,高于正常人组织中的甲基化β值0.080(P=0.002),患者宫颈癌组织中的脂酰转移酶1(LIPT1基因)甲基化β值为0.060,低于正常人组织中的甲基化β值0.092(P=0.009).CDKN2A基因甲基化水平≥0.199的患者的总生存期为14.75年,低于甲基化水平＜0.199患者(17.56年)(P=0.034).基因富集分析结果提示主要涉及Ⅰ型干扰素的反应、DNA复制等生物过程;CDKN2A基因表达与肿瘤微环境中中性粒细胞和树突状细胞的数量呈正相关(P＜0.05),与巨噬细胞的数量呈负相关(P＜0.05).CDKN2A基因变异组的TMB高于未变异组(P=0.019).结论CDKN2A基因甲基化是宫颈癌预后的潜在生物标志物.
The effect of cuproptosis related gene methylation on the prognosis of cervical cancer
To investigate the differences in methylation levels of cuproptosis related genes in cervical cancer and their effects on clinical prognosis.Methods The methylation data of 310 cervical tissue specimens were acquired from public databases.The UALCAN database was used to analyze the methylation level differences of 12 cuproptosis-related genes and study their level in different stages or grades of cervical cancer.Genes with statistically significant differences were selected for prognosis analysis using the EWAS datahub.Finally,gene-enrichment analysis,pathway analysis,immune infiltration analysis,the mutation rate and tumor mutation burden(TMB)of the genes in cervical cancer were analyzed using the cBioportal database.Two independent samples rank-sum test was used for differences in methylation levels and immune cell infiltration;comparative analyses of overall survival were performed using KM survival curves and Log-rank two-sided tests.TMB analyses were performed using the Wilcoxon Test for statistical analyses;Pearson correlation analysis was used for assessment in GSEA and pathway analyses.Results The methylation β value of Cyclin Dependent Kinase Inhibitor 2A(CDKN2A gene)in the cervical cancer tissues of patients was 0.075 which was significantly higher than the methylation β value of 0.049 in normal human tissues(P=0.008).Dihydrolipoamide S-Acetyltransferase(DLAT gene)methylation with a β value of 0.102 was significantly higher than normal human tissue methylation with a β value of 0.08(P=0.002),and the methylation level β value of Lipoyltransferase 1(LIPT1 gene)in cervical cancer tissues was 0.06,which was significantly lower than normal human tissue methylation value of 0.092(P=0.009).Patients with CDKN2A gene methylation levels≥0.199 had an overall survival of 14.75 years,which was lower than that of patients with methylation levels＜0.199(17.56 years)(P=0.034).The results of gene enrichment analysis indicated that it mainly involves biological processes such as the response to type Ⅰ interferon and DNA replication.The expression of CDKN2A gene is positively correlated with the number of neutrophils and dendritic cells in the tumor microenvironment(P＜0.05),and negatively correlated with the number ofmacrophages(P＜0.05).TMB was higher in the group of variants of the CDKN2A gene than in the group of non-variants(P=0.019).Conclusion CDKN2A methylation is a potential biomarker for predicting the prognosis of cervical cancer.

Uterine cervical neoplasmsBiomarkerMethylationPrognosisCuproptosis related gene

丁与、彭嘉琪、陈锦辉、周志伟、吴倩、李萍、刘禹利、谭评、胡燕、谢小兵、温鼎声

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广东药科大学附属第一医院,临床药学重点专科,广州 510080

湖南中医药大学第一附属医院医学检验与病理中心,长沙 410007

宫颈肿瘤 生物标志物 甲基化 预后 铜死亡相关基因

广东省大学生创新创业训练计划广东省大学生创新创业训练计划广东省大学生创新创业训练计划广东省医院药师青年托举研究基金(晴粤药学基金)2022年度广东药科大学临床药学院国家自然科学基金培育基金国家临床重点专科建设项目(临床药学)

S202110573021202210573048202210573008X2023QNTJ36SCP2022-06

2024

10.3760/cma.j.cn114452-20231114-00278

中华检验医学杂志
中华医学会

中华检验医学杂志

CSTPCD北大核心
影响因子：1.402
ISSN：1009-9158
年,卷(期)：2024.47(4)
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