摘要
目的分析牙龈卟啉单胞菌(Porphyromonas gingivalis,Pg)对食管鳞癌(esophageal squamous cell carcinoma,ESCC)选择性自噬接头蛋白p62的表达诱导效应及其与食管癌患者临床病理特征及生存期的相关性。方法采用透射电子显微镜及Western blot法检测Pg对ESCC细胞KYSE150自噬的影响,随后通过共聚焦显微镜检测Pg感染及p62敲降对KYSE150细胞自噬进程的影响,并进一步采用平板克隆、CCK-8及划痕实验检测Pg感染及p62敲降对KYSE150细胞增殖及迁移能力的影响。采用免疫组织化学法检测ESCC组织中Pg感染及p62的表达情况,并分析其与患者临床病理特征的相关性;采用Kaplan-Meier法分析二者对ESCC患者生存期的影响。结果Pg感染初期可通过p62介导KYSE150细胞自噬水平的提高,但随着Pg持续感染进一步诱导p62高表达,则导致ESCC细胞自噬受阻,同时增强ESCC细胞的增殖及迁移能力。ESCC组织中Pg感染与p62表达高于相应癌旁组织,且二者阳性表达呈显著一致性。Pg感染与p62表达阳性的患者多为吸烟、饮酒的男性,其肿瘤分化程度低、有淋巴结转移、临床分期晚,且5年生存期显著缩短。其中Pg感染与p62表达共阳性患者的5年生存期缩短最为显著。结论长期吸烟、饮酒的男性患者感染Pg的风险增高,Pg可通过诱导p62高表达,阻断ESCC细胞自噬,促进其恶性进展。有效清除Pg并抑制其对p62的诱导效应有望成为ESCC新的防治策略。
Objective To explore the expression induction effect of Porphyromonas gingivalis(Pg)on selective autophagy protein p62 in esophageal squamous cell carcinoma(ESCC)and its correlation with the clinicopathological characteristics and survival of the patients.Methods Transmission electron microscopy and Western blot were used to detect the effect of Pg on autophagy of ESCC cell KYSE150.Confocal microscopy was used to detect the effects of Pg infection and p62 knockdown on autophagy of KYSE150 cell.Colony formation assay,CCK-8 and wound healing assay were adopted to detect the effects of Pg infection and p62 knockdown on KYSE150 cell proliferation and migration.Pg infection and p62 expression in ESCC tissues were detected by immunohistochemistry,and their correlation with clinicopathological features of patients was analyzed.Kaplan-Meier method was used to analyze the effects of Pg infection and p62 expression on the survival of ESCC patients.Results In the early stage of Pg infection,the level of autophagy in KYSE150 cells could be increased.However,the continued infection of Pg further induced high expression of p62,which led to inhibition of autophagy in ESCC cells and enhanced the proliferation and migration ability of ESCC cells.Pg infection level and p62 expression in ESCC tissues were higher than that in adjacent tissues,and their consistency was significant.The patients with Pg infection and high expression of p62 were mostly males who had smoking and drinking history,with low differentiation degree,early lymph node metastasis,advanced clinical stage,and shortened 5-year survival.Patients who were co-positive for Pg infection and high p62 expression witnessed the most significant reduction of 5-year survival.Conclusion Male patients who have long-term smoking and drinking history have an increased risk for Pg infection.Pg can inhibit the autophagy of ESCC cells and promote the malignant progression by inducing the high expression of p62.Effective clearance of Pg and inhibition of its induction effect on p62 can provide a scientific basis for the formulation of new ESCC prevention and treatment strategies.
作者
郭艺博
刘怡文
杨海军
代宁涛
孙蔚
米优嘉
张家铭
周福有
原翔
高社干
GuoYibo;Liu Yiwen;Yang Haijun;无(Henan Key Laboratory of Microbiome and Esophageal Cancer Prevention and Treatment,Henan Key Laboratory of Cancer Epigenetics,Cancer Hospital,the First Affiliated Hospital(College of Clinical Medicine)of Henan University of Science and Technology,Luoyang 471003,China;College of Basic Medicine,Henan University of Science and Technology,Luoyang 471003,China;Department of Pathology,Anyang Tumor Hospital,Anyang 455000,China;Department of Thoracic Surgery,Anyang Tumor Hospital,Anyang 455000,China)
出处
《华中科技大学学报（医学版）》
CAS
CSCD
北大核心
2022年第5期592-600,共9页
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
基金
国家自然科学基金资助项目(No.82073029)
河南省科技厅重大项目(No.161100311200)
河南省科技攻关项目(No.212102310670)
河南省医学科技攻关计划联合共建立项项目(No.LHGJ20210585,No.LHGJ20200583,No.LHGJ20200806,No.LHGJ20200811)。
关键词
牙龈卟啉单胞菌
食管鳞癌
P62
预后
Porphyromonas gingivalis
esophageal squamous cell carcinoma
p62
prognosis
