ATG5和PDIA3在宫颈癌组织中的表达及其临床意义  

Expression of ATG5 and PDIA3 in cervical cancer tissues and their clinical significance

作　　者：李秀芳 黄利英 韩毅[2] 刘婷婷[2] 高君琳 田甜[2] LI Xiufang;HUANG Liying;HAN Yi;LIU Tingting;GAO Junlin;TIAN Tian(Department of Obstetrics and Gynecology,Qingdao University Medical Science College,Qingdao 266071,Shandong,China;Department of Gynecology,Affiliated Hospital of Qingdao University,Qingdao 266071,Shandong,China)

机构地区：[1]青岛大学医学部妇产科,山东青岛266071 [2]青岛大学附属医院妇科,山东青岛266000

出　　处：《中国肿瘤生物治疗杂志》2024年第10期1008-1016,共9页Chinese Journal of Cancer Biotherapy

摘　　要：目的:探究免疫原性细胞死亡相关基因——自噬相关基因5(ATG5)和蛋白质二硫键异构酶A3(PDIA3)在宫颈癌组织中的表达及其与患者临床病理特征和预后的相关性、相关信号通路及药物敏感性。方法:收集自2016年1月至2023年12月间青岛大学附属医院60例宫颈癌癌组织标本作为实验组,26例因子宫肌瘤、子宫腺肌症切除的正常宫颈组织标本作为对照组,并收集相应的临床资料。采用免疫组化法检测宫颈癌组织和正常宫颈组织中ATG5、PDIA3蛋白的表达差异,分析其表达与各项临床病理参数之间的关系。基于基因表达水平值的交互式分析平台(GEPIA)在线分析宫颈癌组织中ATG5、PDIA3的表达水平对患者预后的影响,使用基因本体论(GO)、京都基因与基因组百科全书(KEGG)、基因集富集分析(GSEA)探究ATG5和PDIA3基因可能涉及的生物学功能及信号通路,用p RRophetic包分析宫颈癌患者癌组织中ATG5、PDIA3高低表达与患者对化疗药物的敏感性。结果:ATG5、PDIA3在宫颈癌组织中的表达率均显著高于正常宫颈组织(83.3%vs 11.5%,χ^(2)=39.538,P=0.001;75.0%vs 46.2%,χ^(2)=6.753,P=0.009),ATG5的表达水平在肿瘤直径、FIGO分期、淋巴结转移方面的差异显著(均P<0.01);PDIA3的表达水平在肿瘤直径、分化程度、FIGO分期和淋巴结转移方面的差异显著(P<0.05或P<0.01)。ATG5和PDIA3的表达水平呈正相关(r=0.679,P<0.001)。GEPIA在线分析网站预后分析显示,ATG5和PDIA3高表达宫颈癌患者的预后差(均P<0.05)。ATG5和PDIA3主要富集的功能及信号通路包括细胞增殖与分化、抗原加工与提呈、P53结合、Wnt信号通路、MAPK信号通路及mTOR信号通路。结论:ATG5和PDIA3在宫颈癌组织中呈高表达,两者高表达与患者不良预后有关,ATG5和PDIA3参与细胞增殖与分化、抗原加工提呈及多种信号通路,有望成为宫颈癌治疗的潜在靶点。Objective:To investigate the expression of immunogenic cell death-related genes,autophagy associated gene 5(ATG5)and protein disulfide isomerase A3(PDIA3),in cervical cancer tissues,and to explore their correlation with clinicopathological features and prognosis of cervical cancer patients,as well as the related signaling pathways and drug sensitivity.Methods:A total of 60 cervical cancer tissue specimens from the patients treated at Affiliated Hospital of Qingdao University during January 2016 and December 2023 were collected as the experimental group.Additionally,26 normal cervical specimens collected from patients with hysteromyoma and adenomyosis served as the control group.The data of two groups of patients were also collected.The differential protein expression of ATG5 and PDIA3 in cervical cancer tissues and normal cervical tissues was detected by immunohistochemistry,and their relationship with patients'clinicopathological parameters was also analyzed.The influence of ATG5 and PDIA3 expression in cervical cancer tissues on patient prognosis was analyzed using interactive analysis platform(GEPIA).Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG),and Gene Set Enrichment Analysis(GSEA)were utilized to explore their functional roles and signaling pathways associated with ATG5 and PDIA3 genes.The sensitivity of cervical cancer patients to chemotherapeutic drugs was analyzed using the pRRophetic package based on the high and low expression of ATG5 and PDIA3 in cancer tissues.Results:The positive expression rates of ATG5 and PDIA3 in cervical cancer tissues were significantly higher than those in normal cervical tissues(83.3%vs 11.5%,χ^(2)=39.538,P=0.001;75.0%vs 46.2%,χ^(2)=6.753,P=0.009).The expression levels of ATG5 differed notably across patients with different tumor diameter,FIGO stage and lymph node metastasis(all P<0.01),while the expression levels of PDIA3 differed greatly across patients with different tumor diameter,differentiation degree,FIGO stage and lymph node metastasis(P<0.05 or P

关 键 词：宫颈癌 免疫原性细胞死亡 自噬相关基因5 蛋白质二硫键异构酶A3 预后 

分 类 号：R737.33[医药卫生—肿瘤] R730.51[医药卫生—临床医学]