脂肪甘油三酯脂肪酶在头颈部鳞状细胞癌中的表达及相关分子机制  

Expression and related molecular mechanism of adipose triglyceride lipase in squamous cell carcinoma of head and neck

作　　者：肖雪[1] 言柯柯 李丽媚 赵军 张哲[1] 周晓莹 XIAO Xue;YAN Ke-ke;LI Li-mei;ZHAO Jun;ZHANG Zhe;ZHOU Xiao-ying(Department of Otolaryngology-Head and Neck Surgery,First Affiliated Hospital of Guangxi Medical University,Nanning 530021,Guangxi,China;Department of Radiotherapy,First Affiliated Hospital of Guangxi Medical University,Nanning 530021,Guangxi,China;Department of Pediatric Stomatology,Guangxi Medical University College of Stomatology,Nanning 530021,Guangxi,China;Life Science Institute,Guangxi Medical University,Nanning 530021,Guangxi,China)

机构地区：[1]广西医科大学第一附属医院耳鼻咽喉头颈外科,广西南宁市530021 [2]广西医科大学第一附属医院放疗科,广西南宁市530021 [3]广西医科大学口腔医学院-附属口腔医院儿童口腔科,广西南宁市530021 [4]广西医科大学生命科学研究院,广西南宁市530021

出　　处：《广西医学》2022年第14期1636-1642,1689,共8页Guangxi Medical Journal

基　　金：国家自然科学基金(82060511)。

摘　　要：目的 分析脂肪甘油三酯脂肪酶(ATGL)在头颈部鳞状细胞癌(头颈鳞癌)中的表达及相关分子机制。方法 通过UALCAN数据库分析ATGL在头颈鳞癌中的转录和蛋白表达水平,并以人乳头状瘤病毒(HPV)感染状态为分层因素分析ATGL的转录水平;基于GEO数据库的ATGL微阵列数据集进行Meta分析验证ATGL在头颈鳞癌中的转录水平。分别通过UALCAN数据库、Kaplan-Meier Plotter分析ATGL表达与头颈鳞癌分级、患者预后的关系。通过MethSurv分析ATGL CpG岛在头颈鳞癌中的甲基化状态及与患者预后的相关性。通过基因富集分析软件分析ATGL参与调控的信号通路。通过TIMER分析ATGL与头颈鳞癌中免疫细胞浸润的相关性,以及在不同HPV感染状态下与免疫细胞标志物的相关性。结果 在头颈鳞癌组织中,ATGL转录水平和蛋白表达水平均下调(均P<0.05);低分化头颈鳞癌组织中ATGL的蛋白表达较中分化头颈鳞癌组织更低,ATGL低表达的头颈鳞癌患者的生存率更低(均P<0.05)。ATGL CpG岛3个位点的甲基化与患者的预后相关,其中cg04519421、cg09051513位点发生高甲基化的头颈鳞癌患者生存率更低(均P<0.05)。头颈鳞癌中ATGL主要涉及转录因子E2F、DNA损伤检查点G2M、原癌基因MYC、上皮-间质转化、转化生长因子β、Hedgehog、磷脂酰肌醇3-激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白、糖酵解等信号传导通路。ATGL表达水平与B淋巴细胞、CD4~+T淋巴细胞、CD8~+T淋巴细胞、巨噬细胞、中性粒细胞及树突状细胞等免疫细胞浸润水平呈正相关(均P<0.05)。与HPV阴性的头颈鳞癌组织相比,ATGL在HPV阳性的头颈鳞癌组织中相对高表达(P<0.05),且与CD8~+T淋巴细胞、T淋巴细胞(总)、B淋巴细胞、树突状细胞浸润水平的相关性更高。结论 ATGL在头颈鳞癌中呈低表达,是候选的预后评估相关分子标志物。头颈鳞癌细胞可能通过表观遗传机制沉默ATGL的表达,从而促进�Objective To analyze the expression and related molecular mechanism of adipose triglyceride lipase(ATGL) in squamous cell carcinoma of head and neck. Methods The transcription and protein expression levels of ATGL in squamous cell carcinoma of head and neck was analyzed by UALCAN database, and the ATGL transcription level was analyzed by taking human papilloma virus(HPV) infection status as stratification factor. The Meta analysis was used to verify the ATGL transcription level in squamous cell carcinoma of head and neck based on the ATGL micro-array data set of GEO database. The relation of ATGL expression with classification of squamous cell carcinoma of head and neck, and patients′ prognosis was analyzed by the UALCAN database and Kaplan-Meier Plotter, respectively. The correlation of ATGL CpG island methylation status in squamous cell carcinoma of head and neck with patients′ prognosis was analyzed by the MethSurv. The signaling pathway of ATGL involved in regulation was analyzed by the Gene Set Enrichment Analysis software. The correlation of ATGL with infiltration of immune cells in squamous cell carcinoma of head and neck and immune cell markers under different HPV infection were analyzed by the TIMER. Results The transcription level and protein expression level of ATGL was down-regulated in squamous cell carcinoma of head and neck(all P<0.05). The protein expression of ATGL in poorly differentiated squamous cell carcinoma of head and neck tissues was lower than that in moderately differentiated squamous cell carcinoma of head and neck tissues, and the survival rate of patients with low ATGL expression was lower(all P<0.05). The methylation of the three loci of ATGL CpG island correlated with the patients′ prognosis, among which the patients with squamous cell carcinoma of head and neck presenting high methylation at cg04519421 and cg09051513 loci had lower survival rate(all P<0.05). ATGL in squamous cell carcinoma of head and neck mainly involved in transcription factor E2 F, DNA damage checkpoint G

关 键 词：头颈部鳞状细胞癌 脂肪甘油三酯脂肪酶 甲基化 免疫微环境 预后 人乳头状瘤病毒感染 

分 类 号：R739.91[医药卫生—肿瘤]