1、11现代检验医学杂志第 38 卷第 1 期2023 年 1 月J Mod Lab Med,Vol.38,No.1,Jan.2023宫颈癌组织 FBN1 基因甲基化状态与临床病理特征及 预后的相关性研究杨学丽a，安欣a，姜琳娜a，吴倩岚a，江现丽a，魏娉a，薛洁b（邯郸市第一医院 a.病理科；b.妇科，河北邯郸 056002）摘要：目的探究宫颈癌（cervical cancer，CC）组织原纤维蛋白-1（fibrillin-1，FBN1）基因甲基化状态与患者临床病理特征及预后的关系。方法选取 2014 年 6 月 2017 年 4 月邯郸市第一医院诊治的 98 例 CC 患者为研究对象，收集经手
2、术切除的 CC 组织、癌旁组织。甲基化特异性 PCR 法测定 CC 组织、癌旁组织 FBN1 基因甲基化状态；蛋白印迹法检测 CC 组织、癌旁组织 FBN1 蛋白表达水平；对 CC 患者进行为期 5 年的随访，记录患者生存情况；比较 CC 组织和癌旁组织 FBN1 基因甲基化发生率以及 FBN1 基因非甲基化组和 FBN1 基因甲基化组 CC 组织 FBN1 蛋白表达水平；分析 CC 组织 FBN1 基因甲基化状态与患者临床病理特征的关系、FBN1 基因甲基化状态与患者预后的关系以及 CC 患者预后的影响因素。结果CC 组织 FBN1 基因甲基化发生率（60.20%）高于癌旁组织（12.24%
3、），差异有统计学意义（2=48.785，P0.05）；FBN1 基因甲基化组 FBN1 蛋白表达水平（0.610.12）低于 FBN1 基因非甲基化组（1.590.32），差异有统计学意义（t=21.401，P0.05）。CC组织FBN1基因甲基化状态与患者TNM分期、高危型人乳头瘤病毒DNA（high risk-human papillomavirus DNA，HR-HPV DNA）、淋巴结转移相关（2=7.578，8.140，7.814，均 P0.05）；FBN1 基因甲基化组 CC 患者 5 年累积生存率为 38.98%，低于 FBN1 基因非甲基化组（76.92%），差异有统计学意义（
4、2=13.464，P0.05）。HR-HPV DNA阳性OR（95%CI）:2.534（1.5774.072），有淋巴结转移OR（95%CI）:2.426（1.5463.808），TNM 分期 期 OR（95%CI）:2.702（1.6334.471）和 FBN1 基因甲基化 OR（95%CI）:2.394（1.5313.743）是影响 CC 患者预后的独立危险因素（P0.05）。结论CC 患者癌组织中 FBN1 基因甲基化水平较高，其与 TNM 分期、HR-HPV DNA 和淋巴结转移等临床病理特征及预后相关，为临床诊治 CC 和评估 CC 患者预后提供新方向。关键词：宫颈癌；原纤维蛋白-1
5、；基因甲基化；临床病理特征中图分类号：R737.33；R730.43文献标识码：A文章编号:1671-7414（2023）01-011-05doi:10.3969/j.issn.1671-7414.2023.01.003Correlation between Methylation Status of FBN1 Gene in Cervical Cancer Tissue and Clinicopathological Features and PrognosisYANG Xue-lia,AN Xina,JIANG Lin-naa,WU Qian-lana,JIANG Xian-lia,WEI
6、 Pinga,XUE Jieb(a.Department of Pathology；b.Department of Gynecology,the First Hospital of Handan,Hebei Handan 056002,China)Abstract:ObjectiveTo explore the relationship between the methylation status of fibrillin-1(FBN1)gene and the clinicopathological characteristics and prognosis of cervical canc
7、er(CC)tissue.MethodsFrom June 2014 to April 2017,98 CC patients diagnosed and treated in the First Hospital of Handan were regarded as the research objects,and the surgically resected CC tissue and paracancerous tissue were collected.Methylation-specific PCR method was applied to determine the methy
8、lation status of FBN1 gene in CC tissue and paracancerous tissue.Western blot was applied to detection of FBN1 protein expression levels in CC tissue and paracancerous tissue.CC patients were followed up for 5 years and their survival conditions were recorded,the methylation rate of FBN1 gene in CC
9、tissue and paracancerous tissue and the expression level of FBN1 protein in CC tissue of FBN1 gene non-methylation group and FBN1 gene methylation group were compared.The relationship between the methylation status of FBN1 gene in CC tissues and the clinicopathological characteristics of patients,th
10、e relationship between the methylation status of FBN1 gene and the prognosis of patients and the factors affecting the prognosis of CC patients were analyzed.ResultsThe incidence of FBN1 gene methylation in CC tissues(60.20%)was higher than that in paracancerous tissues(12.24%),and the difference wa
11、s statistically significant(2=48.785,P0.05).The expression level of FBN1 protein in FBN1 gene methylation group(0.610.12)was lower than that in FBN1 gene non-methylation group(1.590.32),and the difference was statistically significant(t=21.401,P0.05).The methylation status of FBN1 gene in CC tissues
12、 was correlated with 基金项目：河北省医学科学研究课题计划项目（20200188）。作者简介：杨学丽（1979-），女，硕士，副主任医师，研究方向：妇科肿瘤病理，E-mail：。12现代检验医学杂志第 38 卷第 1 期2023 年 1 月J Mod Lab Med,Vol.38,No.1,Jan.2023TNM staging,high risk-human papillomavirus DNA(HR-HPV DNA),and lymph node metastasis(2=7.578,8.140,7.814,all P0.05).The 5-year cumulativ
13、e survival rate of CC patients in the FBN1 gene methylation group(38.98%)was lower than that in the FBN1 gene non-methylation group(76.92%),the difference was statistically significant(2=13.464,P0.05).HR-HPV DNA positive OR(95%CI):2.534(1.5774.072),lymph node metastasis OR(95%CI):2.426(1.5463.808),T
14、NM stage OR(95%CI):2.702(1.6334.471)and FBN1 gene methylation OR(95%CI):2.394(1.5313.743)were independent risk factors affecting the prognosis of CC patients(P0.05).ConclusionThe level of FBN1 gene methylation in cancer tissues of CC patients was relatively high,which was related to clinicopathologi
15、cal characteristics such as TNM staging,HR-HPV DNA and lymph node metastasis,and prognosis,and it provides a new direction for clinical diagnosis and treatment of CC and evaluation of the prognosis of CC patients.Keywords:cervical cancer；fibrillin-1；gene methylation；clinicopathological features宫颈癌（c
16、ervical cancer，CC）是一种发生率较高的妇科肿瘤，其早期多无明显症状，随着疾病发展，会出现阴道排液、流血症状，且病死率较高1-2。因此，寻找与 CC 病理变化相关，且可评估 CC 患者预后的指标，对制定个体化治疗方案有积极意义。既往报道显示，CC 发生发展与机体免疫功能异常、染色体畸变、人乳头瘤病毒（human papillomavirus，HPV）感染、DNA 异常甲基化等有关3-4。研究发现，原纤维蛋白-1（fibrillin-1，FBN1）在卵巢癌中表达下调，其可能在卵巢癌病理发展中起作用5；且张建华等6研究发现食管癌组织 FBN1 基因甲基化发生率较高，FBN1 基因甲基化与食管癌病变过程密切相关。但 FBN1 基因甲基化在 CC 患者中的发生情况，及其与 CC 患者预后、临床病理特征的关系尚不明确。因此，本文通过甲基化特异性 PCR（methylation-specific PCR，MSP）法测定 CC 患者癌组织 FBN1 基因甲基化情况，旨在分析其与 CC 患者预后、临床病理特征的关系。1材料与方法1.1研究对象选取 2014 年 6 月 2017 年 4
