[1]杨学丽a,安 欣a,姜琳娜a,等.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[J].现代检验医学杂志,2023,38(01):11-15.[doi:10.3969/j.issn.1671-7414.2023.01.003]
 YANG Xue-lia,AN Xina,JIANG Lin-naa,et al.Correlation between Methylation Status of FBN1 Gene in Cervical Cancer Tissue and Clinicopathological Features and Prognosis[J].Journal of Modern Laboratory Medicine,2023,38(01):11-15.[doi:10.3969/j.issn.1671-7414.2023.01.003]
点击复制

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()
分享到:

《现代检验医学杂志》[ISSN:/CN:]

卷:
第38卷
期数:
2023年01期
页码:
11-15
栏目:
论著
出版日期:
2023-01-15

文章信息/Info

Title:
Correlation between Methylation Status of FBN1 Gene in Cervical Cancer Tissue and Clinicopathological Features and Prognosis
文章编号:
1671-7414(2023)01-011-05
作者:
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)
Author(s):
YANG Xue-lia AN Xina JIANG Lin-naa WU Qian-lana JIANG Xian-lia WEI Pinga XUE Jieb
(a.Department of Pathology;b.Department of Gynecology, the First Hospital of Handan, Hebei Handan 056002, China)
关键词:
宫颈癌原纤维蛋白-1基因甲基化临床病理特征
分类号:
R737.33;R730.43
DOI:
10.3969/j.issn.1671-7414.2023.01.003
文献标志码:
A
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%),差异有统计学意义(χ2=48.785,P<0.05);FBN1 基因甲基化组FBN1 蛋白表达水平(0.61±0.12)低于FBN1 基因非甲基化组(1.59±0.32),差异有统计学意义(t=21.401,P<0.05)。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(highrisk-human papillomavirus DNA,HR-HPV DNA)、淋巴结转移相关(χ2=7.578,8.140,7.814,均P<0.05);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(χ2=13.464,P<0.05)。HR-HPV DNA 阳性[OR(95%CI): 2.534(1.577~4.072)],有淋巴结转移[OR(95%CI): 2.426(1.546~3.808)],TNM 分期Ⅲ ~ Ⅳ期[OR(95%CI): 2.702(1.633~4.471)] 和FBN1 基因甲基化[OR(95%CI): 2.394(1.531~3.743)]是影响CC 患者预后的独立危险因素(P<0.05)。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。
Abstract:
Objective To explore the relationship between the methylation status of fibrillin-1 (FBN1) gene and the clinicopathological characteristics and prognosis of cervical cancer (CC) tissue. Methods From 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 methylation 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 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, the relationship between the methylation status of FBN1 gene and the prognosis of patients and the factors affecting the prognosis of CC patients were analyzed. Results The incidence of FBN1 gene methylation in CC tissues (60.20%) was higher than that in paracancerous tissues (12.24%) , and the difference was statistically significant (χ2=48.785, P<0.05). The expression level of FBN1 protein in FBN1 gene methylation group (0.61±0.12) was lower than that in FBN1 gene non-methylation group(1.59±0.32), and the difference was statistically significant(t=21.401, P<0.05). The methylation status of FBN1 gene in CC tissues was correlated with TNM staging, high risk-human papillomavirus DNA (HR-HPV DNA), and lymph node metastasis (χ2=7.578, 8.140, 7.814, all P<0.05). The 5-year cumulative 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 (χ2=13.464, P<0.05).HR-HPV DNA positive [OR(95%CI): 2.534(1.577~4.072)], lymph node metastasis [OR(95%CI): 2.426(1.546~3.808)],TNM stageⅢ ~ Ⅳ [OR(95%CI): 2.702(1.633~4.471)] and FBN1 gene methylation [OR(95%CI): 2.394(1.531~3.743)] were independent risk factors affecting the prognosis of CC patients (P<0.05). Conclusion The level of FBN1 gene methylation in cancer tissues of CC patients was relatively high, which was related to clinicopathological 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.

参考文献/References:

[1] WANG Lina, HUANG Kejin, WANG Le, et al.Overexpression of Ubiquilin4 is associated with poor prognosis in patients with cervical cancer [J]. World J Clin Cases, 2022, 10(9):2783-2791.
[2] MOTA S D S, OTA?O S S, MURTA E F C, et al.Blood count and fasting blood glucose level in the assessment of prognosis and survival in advanced cervical cancer [J]. Rev Assoc Med Bras (1992), 2022,68(2):234-238.
[3] 方芳, 吴玲, 魏善闯, 等. 宫颈癌患者血清LCN2 水平表达与HPV 病毒载量及临床分期的相关研究[J].现代检验医学杂志, 2022, 37(2):80-84, 99.
FANG fang, WU Ling, WEI Shanchuang, et al.Correlation of expression of serum LCN2 level with HPV load and clinical stage in patients with cervical cancer [J]. Journal of Modern Laboratory Medicine,2022, 37(2):80-84, 99.
[4] LI Chunxiao, KE Jinxiu, LIU Jiangyi, et al. DNA methylation data-based molecular subtype classification related to the prognosis of patients with cervical cancer[J]. J Cell Biochem, 2020, 121(3):2713-2724.
[5] KERSLAKE R , HALL M , VAGNARELLI P , et al. A pancancer overview of FBN1, asprosin and its cognate receptor OR4M1 with detailed expression profiling in ovarian cancer[J]. Oncology Letters, 2021, 22(3):650.
[6] 张建华, 郭琪, 周章剑, 等. FBN1,FBN2 基因甲基化与食管癌的相关性研究[J]. 现代肿瘤医学, 2018, 26(4) : 523-526.
ZHANG Jianhua, GUO Qi, ZHOU Zhangjian, et al.Study on the correlation between FBN1/FBN2 gene methylation and esophageal carcinoma [J]. Journal of Modern Oncology, 2018, 26(4):523-526.
[7] 中华人民共和国国家卫生和计划生育委员会. 宫颈癌及癌前病变规范化诊疗指南(试行)[J]. 中国医学前沿杂志(电子版), 2013, 5(8):37-46.
National Health and Family Planning Commission of the People’s Republic of China. Guidelines for standardized diagnosis and treatment of cervical cancer and precancerous lesions (Trial)[J]. Chinese Journal of the Frontiers of Medical Science(Electronic Version) ,2013, 5(8):37-46.
[8] 高红敏, 杨红英, 刘鑫. 血清中microRNA-106b 对宫颈癌患者的早期诊断及预后预测价值[J]. 现代检验医学杂志,2020,35(6):85-86,182.
GAO Hongmin, YANG Hongying, LIU Xin. Value analysis of serum microRNA-106b in early diagnosis of cervical cancer [J]. Journal of Modern Laboratory Medicine, 2020,35(6):85-86, 182.
[9] ZHANG Chunyu , LIAO Yuandong , LIU Pan , et al.FABP5 promotes lymph node metastasis in cervical cancer by reprogramming fatty acid metabolism[J].Theranostics, 2020, 10(15):6561-6580.
[10] ZHOU Y , SHEN L , WANG Y Z , et al. The potential of ciRS-7 for predicting onset and prognosis of cervical cancer[J]. Neoplasma, 2019, 67(2):312-322.
[11] SHI Mai, TSUI S K, WU Hao , et al. Pan-cancer analysis of differential DNA methylation patterns[J].BMC Medical Genomics, 2020, 13(Suppl 10):154.
[12] CHEN Hongxia, LI Hongying , WANG Lei , et al.A 5-gene DNA methylation signature is a promising prognostic biomarker for early-stage cervical cancer[J].Journal of Obstetrics and Gynaecology, 2022,42(2):327-332.
[13] KONG Linghua, WANG Linhai, WANG Ziyun, et al. DNA methylation for cervical cancer screening:A training set in China[J].Clin Epigenetics, 2020,12(1):91.
[14] MUTHU M L, REINHARDT D P. Fibrillin-1 and fibrillin-1-derived asprosin in adipose tissue function and metabolic disorders[J].J Cell Commun Signal,2020, 14(2):159-173.
[15] CHE Xiaoxia, JIAN Fangfang, WANG Ying, et al.FBXO2 promotes proliferation of endometrial cancer by ubiquitin-mediated degradation of FBN1 in the regulation of the cell cycle and the autophagy pathway[J]. Front Cell Dev Biol, 2020, 8:843.
[16] WANG Zhi, TU Lei, CHEN Minfeng, et al. Identification of a tumor microenvironment-related seven-gene signature for predicting prognosis in bladder cancer[J].BMC Cancer, 2021, 21(1):692.
[17] 尹建浩, 张昊, 孟磊, 等. 粪便SPG20, FBN1 及VIM 基因启动子甲基化联合检测在结直肠癌诊断中的意义[J]. 陕西医学杂志, 2017, 46(4): 414-416.
YIN Jianhao, ZHANG Hao, MENG Lei, et al.Detection of hypermethylated SPG20, FBN1 and VIM in stool samples of patients with colorectal cancer [J].Shaanxi Medical Journal, 2017, 46(4): 414-416.
[18] ZHANG Chunhe , FU Shaowei , WANG Luyue , et al.The value and clinical significance of ZNF582 gene methylation in the diagnosis of cervical cancer [J].Onco Targets Ther, 2021, 14:403-411.
[19] LIU Haifeng, MENG Xia, WANG Jingyi. Real time quantitative methylation detection of PAX1 gene in cervical cancer screening[J]. Int J Gynecol Cancer,2020, 30(10):1488-1492.
[20] 陈艳, 牛三强, 胡卫平, 等. 宫颈癌ING4 基因启动子区甲基化状态及其临床意义[J]. 安徽医科大学学报,2020,55(10):1620-1624.
CHEN Yan, NIU Sanqiang, HU Weiping, et al.Methylation status of ING4 gene promoter region in cervical cancer and its clinical significance [J]. Acta Universitatis Medicinalis Anhui, 2020, 55(10):1620-1624.
[21] KOROKNAI V, SZ?SZ I, HERNANDEZ-VARGAS H,et al. DNA hypermethylation is associated with invasive phenotype of malignant melanoma[J]. Exp Dermatol,2020, 29(1):39-50.

相似文献/References:

[1]田英,王双勇,赵雅,等.宫颈癌组织细胞中Numb基因表达及相关性研究[J].现代检验医学杂志,2015,30(06):42.[doi:10.3969/j.issn.1671-7414.2015.06.012]
 TIAN Ying,WANG Shuang-yong,ZHAO Ya,et al.Study on Correlation and Expression of Numb Gene in Cervical Cancer[J].Journal of Modern Laboratory Medicine,2015,30(01):42.[doi:10.3969/j.issn.1671-7414.2015.06.012]
[2]顾益凤,朱自力,史跃燕,等.血浆硫氧还蛋白还原酶水平检测对宫颈癌早期诊断的价值研究[J].现代检验医学杂志,2019,34(02):40.[doi:10.3969/j.issn.1671-7414.2019.02.011]
 GU Yi-feng,ZHU Zi-li,SHI Yue-yan,et al.Study on the Value of Plasma Thioredoxin Reductase Levelin the Early Diagnosis of Cervical Cancer[J].Journal of Modern Laboratory Medicine,2019,34(01):40.[doi:10.3969/j.issn.1671-7414.2019.02.011]
[3]陈 慎,杜明君,宋雅琴.宫颈组织HPV DNA与血清Chemerin,Leptin水平联合检测对宫颈癌早期诊断的价值分析[J].现代检验医学杂志,2019,34(03):42.[doi:10.3969/j.issn.1671-7414.2019.03.010]
 CHEN Shen,DU Ming-jun,SONG Ya-qin.Value of Combined Detection of HPV DNA and Serum Levelsof Chemerin and Leptin in Early Diagnosis of Cervical Cancer[J].Journal of Modern Laboratory Medicine,2019,34(01):42.[doi:10.3969/j.issn.1671-7414.2019.03.010]
[4]周 静,李 智,周 玉,等.宫颈癌组织中 Ep-CAM和 Ki67的表达及临床意义[J].现代检验医学杂志,2019,34(06):24.[doi:10.3969 / j.issn.1671-7414.2019.06.006]
 ZHOU Jing,LI Zhi,ZHOU Yu,et al.Expression and Clinicd Value of Ep-CAM and Ki67 in the Cervial Carcinoma Tissue[J].Journal of Modern Laboratory Medicine,2019,34(01):24.[doi:10.3969 / j.issn.1671-7414.2019.06.006]
[5]徐晓锋a,王 纯b,卢国丰a,等.宫颈癌患者 Kruppel 样因子 6,p21 蛋白表达水平与病理特征及化疗敏感性的相关性分析[J].现代检验医学杂志,2020,35(06):12.[doi:doi:10.3969/j.issn.1671-7414.2020.06.004]
 XU Xiao-feng a,WANG Chun b,LU Guo-feng a,et al.Correlation Analysis of KLF6 and p21 Protein Expression Levels andPathological Features and Chemotherapy Sensitivity in Patientswith Cervical Cancer[J].Journal of Modern Laboratory Medicine,2020,35(01):12.[doi:doi:10.3969/j.issn.1671-7414.2020.06.004]
[6]高红敏,杨红英,刘 鑫.血清中 microRNA-106b 对宫颈癌患者的早期诊断及预后预测价值[J].现代检验医学杂志,2020,35(06):85.[doi:doi:10.3969/j.issn.1671-7414.2020.06.020]
 GAO Hong-min,YANG Hong-ying,LIU Xin.Value Analysis of Serum microRNA-106b in Early Diagnosis ofCervical Cancer[J].Journal of Modern Laboratory Medicine,2020,35(01):85.[doi:doi:10.3969/j.issn.1671-7414.2020.06.020]
[7]赵白信,于慧娟,焦方杰,等.经阴道彩色多普勒超声联合血清 miR-130a,miR-425-5p 水平检测对宫颈癌的诊断效能分析[J].现代检验医学杂志,2021,36(03):43.[doi:10.3969/j.issn.1671-7414.2021.03.010]
 ZHAO Bai-xin,YU Hui-juan,JIAO Fang-jie,et al.Analysis of Diagnostic Efficacy of Transvaginal Color Doppler UltrasoundCombined with Serum miR-130a and miR-425-5p Levels in Cervical Cancer[J].Journal of Modern Laboratory Medicine,2021,36(01):43.[doi:10.3969/j.issn.1671-7414.2021.03.010]
[8]张治洋,李功娟.10株宫颈癌细胞系中MALAT1的表达及其对顺铂敏感性的影响[J].现代检验医学杂志,2021,36(05):110.[doi:10.3969/j.issn.1671-7414.2021.05.024]
 ZHANG Zhi-yang,LI Gong-juan.Expression of MALAT1 in 10 Cervical Cancer Cell Lines and Its Effect onCisplatin Sensitivity[J].Journal of Modern Laboratory Medicine,2021,36(01):110.[doi:10.3969/j.issn.1671-7414.2021.05.024]
[9]郝艳芳,刘亚荣,黄玲玲,等.miRNA-195靶向调控 CCND2和 MYB抑制宫颈癌细胞增殖、迁移的机制研究[J].现代检验医学杂志,2022,37(01):130.[doi:10.3969/j.issn.1671-7414.2022.01.026]
 HAO Yan-fang,LIU Ya-rong,HUANG Ling-ling,et al.Study on the Mechanism of miRNA-195 Targeting CCND2 and MYB to Inhibit the Proliferation and Migration of Cervical Cancer Cells[J].Journal of Modern Laboratory Medicine,2022,37(01):130.[doi:10.3969/j.issn.1671-7414.2022.01.026]
[10]方 芳,吴 玲,魏善闯,等.宫颈癌患者血清LCN2水平表达与HPV病毒载量及临床分期的相关研究[J].现代检验医学杂志,2022,37(02):80.[doi:10.3969/j.issn.1671-7414.2022.02.017]
 FANG Fang,WU Ling,WEI Shan-chuang,et al.Correlation of Expression of Serum LCN2 Level with HPV Load and Clinical Stage in Patients with Cervical Cancer[J].Journal of Modern Laboratory Medicine,2022,37(01):80.[doi:10.3969/j.issn.1671-7414.2022.02.017]

备注/Memo

备注/Memo:
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:yangxueli328@163.com。
更新日期/Last Update: 2023-01-15