宫颈腺癌中ProEXC和PRMT5的表达及其临床意义

Expression of ProEXC and PRMT5 in cervical adenocarcinoma and their clinical significance

观察ProEXC蛋白和PRMT5蛋白在宫颈腺癌及癌旁组织中的表达,探讨ProEXC和PRMT5的表达与宫颈腺癌辅助诊断及临床病理参数间的关系。收集苏州大学附属第二医院2015—2020年确诊的宫颈腺癌标本88例,采用免疫组化的方法分别检测宫颈腺癌及癌旁组织中ProEXC和PRMT5的表达并进行分析。利用肿瘤基因组图谱数据库(TCGA)分析ProEXC和PRMT5与宫颈腺癌患者的预后相关性及其相关的基因通路。选取基因表达数据库(GEO)中GSE39293数据集,对宫颈腺癌细胞株(HELA)经抗病毒药物处理前后ProEXC和PRMT5的表达量进行了对比分析。在宫颈腺癌组织中,ProEXC蛋白表达率(95.5%比4.6%,P<0.001)和PRMT5蛋白表达率(81.8%比26.1%,P<0.001)均高于癌旁组织,且其表达均与肿瘤的T分期、有无淋巴结转移及有无人乳头瘤病毒(HPV)感染相关(P<0.05)。TCGA数据库分析显示,PRMT5和ProEXC中MCM2高表达患者的总体生存率较低表达患者低(均P<0.05)。在GSE39293数据集中,经西多福韦处理后细胞中MCM2的表达减少(9.34比9.68,P<0.001),PRMT5表达量下降,但差异无统计学意义(8.16比8.26,P=0.087),TOP2A表达无明显改变(8.54比8.42,P=0.056)。耐药组中PRMT5(8.42比8.16,P=0.002)和MCM2(9.51比9.34,P=0.029)表达增加,而TOP2A表达下降(8.06比8.54,P<0.001)。GSEA分析提示ProEXC高表达主要影响细胞周期通路,而PRMT5高表达主要影响RNA剪接体通路。本研究发现,ProEXC蛋白和PRMT5蛋白在宫颈腺癌组织中呈高表达且高表达组预后更差,与宫颈腺癌临床病理特征有一定相关性,可能与其影响细胞周期和RNA合成通路有关,提示其可能在宫颈腺癌的进展中发挥重要作用。

This study observed the expression of ProEXC protein and PRMT5 protein in cervical adenocarcinoma and adjacent tissues,exploring the relationship between the expression of ProEXC and PRMT5 and the auxiliary diagnosis of cervical adenocarcinoma,as well as the clinical pathological parameters.A total of 88 specimens diagnosed with cervical adenocarcinoma from the Second Affiliated Hospital of Soochow University between 2015 and 2020 were collected.Immunohistochemistry was employed to detect the expression of ProEXC and PRMT5 in cervical adenocarcinoma and adjacent tissues,and statistical analysis was conducted.The Cancer Genome Atlas(TCGA)database was utilized to analyze the correlation between the prognosis of cervical adenocarcinoma patients and the expression of ProEXC and PRMT5,as well as their related gene pathways.The GSE39293 dataset from the Gene Expression Omnibus(GEO)was selected to compare the expression levels of ProEXC and PRMT5 in cervical adenocarcinoma cell lines(HELA)before and after antiviral drug treatment.In cervical adenocarcinoma tissues,the expression of ProEXC protein(95.5%vs 4.6%,P<0.001)and PRMT5 protein(81.8%vs 26.1%,P<0.001)was significantly higher than in surrounding adjacent tissues.Their expression was correlated with the tumor′s T stage,lymph node metastasis,and human papillomavirus(HPV)infection(P<0.05).TCGA database analysis showed that patients with high expression of MCM2 in PRMT5 and ProEXC had a lower overall survival rate(P<0.05),while the expression of TOP2A was not significantly correlated with survival.In the GSE39293 dataset,the expression of MCM2(9.34 vs 9.68,P<0.001)and PRMT5(8.16 vs 8.26,P=0.087)in cells decreased after treatment with cidofovir,while TOP2A(8.54 vs 8.42,P=0.056)expression did not change significantly.In the drug-resistant group,the expression of PRMT5(8.42 vs 8.16,P=0.002)and MCM2(9.51 vs 9.34,P=0.029)increased,while TOP2A(8.06 vs 8.54,P<0.001)expression decreased.Gene set enrichment analysis(GSEA)suggested that high expression of ProEXC mainly affected the cell cycle pathway,while high expression of PRMT5 mainly affected the RNA splicing pathway.This study found that ProEXC protein and PRMT5 protein were highly expressed in cervical adenocarcinoma tissues,and the high-expression group had a poorer prognosis,showing a certain correlation with the clinical and pathological characteristics of cervical adenocarcinoma.This may be related to their influence on the cell cycle and RNA synthesis pathways,suggesting their potential significant roles in the progression of cervical adenocarcinoma.