徐志红;邓莹;
XU Zhihong;DENG Ying;Department of Reproductive Genetics,People's Hospital of Deyang City;National Center for Birth Defect Monitoring,West China Second University Hospital,Sichuan University;

• 1:德阳市人民医院生殖遗传科
• 2:四川大学华西第二医院中国出生缺陷监测中心

摘要(Abstract)：

目的:探讨子宫颈鳞状细胞癌患者分泌型卷曲相关蛋白(SFRP)基因甲基化与临床病理特征及人乳头瘤病毒(HPV)感染的关系。方法:选取87例子宫颈鳞状细胞癌患者术中切除的癌组织及配对癌旁正常组织,采用甲基化特异性聚合酶链式反应(MSP)法检测组织中SFRP基因甲基化率,采用实时荧光定量聚合酶链反应(q-PCR)检测子宫颈鳞状细胞癌患者HPV感染情况,采用Spearman相关分析子宫颈鳞状细胞癌患者SFRP基因甲基化水平与其临床病理特征及HPV感染的相关性。结果:子宫颈鳞状细胞癌组织中SFRP基因甲基化率高于癌旁正常组织,差异有统计学意义(P <0.05);不同年龄、肿瘤直径、淋巴结转移、浸润深度的子宫颈鳞状细胞癌患者癌组织SFRP基因甲基化率比较,差异无统计学意义(P> 0.05);不同WHO病理分级、FIGO分期的子宫颈鳞状细胞癌患者癌组织SFRP基因甲基化率比较,差异具有统计学意义(P <0.05); HPV感染阳性子宫颈鳞状细胞癌患者癌组织SFRP基因甲基化率显著高于HPV感染阴性子宫颈鳞状细胞癌患者,差异有统计学意义(P <0.05); SFRP基因甲基化率与子宫颈鳞状细胞癌患者年龄、肿瘤直径、淋巴结转移、浸润深度无相关性(P>0.05),与子宫颈鳞状细胞癌患者的WHO病理分级、FIGO分期、HPV感染呈正相关(r=0.445、0.305、0.260,P <0.05)。结论:SFRP基因甲基化率与子宫颈鳞状细胞癌患者的WHO病理分级、FIGO分期、HPV感染呈正相关,有望成为子宫颈鳞状细胞癌诊断的生物标志物。
Objective: To investigate the relationship between methylation of secreted frizzled-related protein( SFRP) gene and clinicopathological features and human papillomavirus( HPV) infection in patients with cervical squamous cell carcinoma. Methods: 87 patients with cervical squamous cell carcinoma were enrolled; cancer tissues and adjacent normal tissues were collected. The methylation rate of SFRP gene was detected by methylation specific polymerase chain reaction( MSP); Real time fluorescence quantitative polymerase chain reaction( q-PCR) was used to detect HPV infection in patients with cervical squamous cell carcinoma; Spearman correlation was used to analyze the correlation between the methylation rate of SFRP gene and the clinicopathological characteristics and HPV infection. Results: The methylation rate of SFRP gene in cancer tissues was significantly higher than that in adjacent normal tissues( P < 0. 05). The methylation rate of SFRP gene had no significant difference among patients with different age,tumor diameter,lymph node metastasis and invasion depth( P > 0. 05),while had significant difference among patients with different WHO grades and FIGO stages( P < 0. 05). The methylation rate of SFRP gene in HPV positive patients was higher than that of HPV negative patients( P < 0. 05). The methylation rate of SFRP gene was not correlated with age,tumor diameter,lymph node metastasis and invasion depth( P > 0. 05),while was positively correlated with WHO grades,FIGO stages and HPV infection( r = 0. 445,0. 305,0. 260,P < 0. 05).Conclusion: The methylation rate of SFRP gene has positive correlation with the WHO pathological grade,FIGO stage and HPV infection in patients with cervical squamous cell carcinoma,which is expected to be a biomarker for clinical diagnosis.

关键词(KeyWords)： 癌,鳞状细胞;子宫颈鳞状细胞癌;分泌型卷曲相关蛋白;基因甲基化;临床病理特征;人乳头瘤病毒
carcinoma,squamous cell;cervical squamous cell carcinoma;secretory curl associated protein(SFRP);gene methylation;clinicopathological features;human papillomavirus(HPV)

Abstract:

Keywords:

基金项目(Foundation): 四川省卫生厅科研课题(130439)

作者(Authors): 徐志红;邓莹;
XU Zhihong;DENG Ying;Department of Reproductive Genetics,People's Hospital of Deyang City;National Center for Birth Defect Monitoring,West China Second University Hospital,Sichuan University;

DOI: 10.19367/j.cnki.2096-8388.2020.10.017

参考文献(References)：

• [1]王稳，伏世杰，张师前．2017 ESMO《子宫颈癌临床实践指南:诊断、治疗和随访》解读[J]．医学综述，2018,12(10):2345-2348.
• [2]KALLIOPI P,GEORGIA K,VASILIKI L,et al. Novel structural approaches concerning HPV proteins:Insight into targeted therapies for cervical cancer(Review)[J].Oncology Reports,2018,10(7):2130-2135.
• [3]THOMPSON B,BARRINGTON W E,BRIANT K J,et al. Educating latinas about cervical cancer and HPV:a pilot randomized study[J]. Cancer Causes&Control,2019,11(5):2310-2315.
• [4]HEINOSALO T,GABRIEL M,KALLIO L,et al. Secreted frizzled-related protein 2(SFRP2)expression promotes lesion proliferation via canonical WNT signaling and indicates lesion borders in extraovarian endometriosis[J].Hum Reprod,2018,33(5):817-831.
• [5]LIU J,ZHU H,WANG H,et al. Methylation of secreted frizzled-related protein 1(SFRP1)promoter downregulates Wnt/β-catenin activity in keloids[J]. Journal of Molecular Histology,2018,49(2):1-9.
• [6]MO S,SU Z,HENG B,et al. SFRP1 promoter methylation and renal carcinoma risk:a systematic review and meta-analysis[J]. Journal of Nippon Medical School,2018,85(2):78-86.
• [7]FICHT A L,ILANA L A,PHELPS B R. Eliminating cervical cancer:promising developments in primary prevention[J]. Cancer,2019,20(8):2356-2359.
• [8]LI M,DU X,LU M,et al. Prevalence characteristics of single and multiple HPV infections in women with cervical cancer and precancerous lesions in Beijing,China[J].Journal of Medical Virology,2019,91(3):473-475.
• [9]戴永刚，张乃馨，穆家康．HPV亚型与子子宫颈癌前病变及癌变的关系研究[J]．中国肿瘤临床与康复，2018,2(6):8756-8757.
• [10]CORCORAN B,CLARKE A,BARRETT T. Rapid response to HPV vaccination crisis in Ireland[J]. The Lancet,2018,391(5):2103-2105.
• [11]HERVL,CCILE S,MORO M R,et al. HPV vaccination rate in french adolescent girls:an example of vaccine distrust[J]. Archives of Disease in Childhood,2017,103(8):313887-313890.
• [12]JESPER W,ANNI A,PER G. In-tube DNA methylation profiling by fluorescence melting curve analysis[J].Clinical Chemistry,2018,2(7):788-791.
• [13]钟焱，徐慧，彭凤兰．DNA甲基化在基因表达调控中的意义及研究进展[J]．中国医药导报，2019,4(14):33-36.
• [14]沙英娇，何赏，王成彬．非小细胞肺癌DNA甲基化研究进展[J]．中华检验医学杂志，2017,40(6):475-477.
• [15]VERLAAT W,SNIJDERS P J F,NOVIANTI P W,et al. Genome-wide DNA methylation profiling reveals methylation markers associated with 3q gain for detection of cervical precancer and cancer[J]. Clinical Cancer Research An Official Journal of the American Association for Cancer Research,2017,23(14):2641-2645.
• [16]BAARSMA H A, KNIGSHOFF M．‘WNT-er is coming’:WNT signalling in chronic lung diseases[J].Thorax,2017,72(8):209753-209755.
• [17]郭玉霞，马利国，陈递林，等．Wnt信号通路成分相关因子在卵巢癌中的表达以及临床预后价值[J]．山西医药杂志，2018,47(13):1245-1247.
• [18]刘学刚，刘艳彩，吴春平，等．CD151对结肠癌中Wnt信号通路变化的影响[J]．中国医药导报，2018,15(16):8765-8767.
• [19]REN J,JIAN F,JIANG H,et al. Decreased expression of SFRP2 promotes development of the pituitary corticotroph adenoma by upregulating Wnt signaling[J]. International Journal of Oncology, 2018, 52(6):1934-1940.
• [20]WU F,LI J,GUO N,et al. MiRNA-27a promotes the proliferation and invasion of human gastric cancer MGC803 cells by targeting SFRP1 via Wnt/β-catenin signaling pathway[J]. American Journal of Cancer Research,2017,7(3):405-416.
• [21]GUO T,GUO L,FAN Y,et al. Aqueous humor levels of TGFβ2 and SFRP1 in different types of glaucoma[J].BMC Ophthalmology,2019,19(1):5679-5681.
• [22]ZHANG X,RONG X,CHEN Y,et al. Methylation-mediated loss of SFRP2 enhances invasiveness of non-small cell lung cancer cells[J]. Human&Experimental Toxicology,2018,37(2):155-157.
• [23]DUAN H,YAN Z,CHEN W,et al. TET1 inhibits EMT of ovarian cancer cells through activating Wnt/β-catenin signaling inhibitors DKK1 and SFRP2[J]. Gynecologic Oncology,2017,147(2):2301-2305.
• [24]CHENG Y Y,MOK E,TAN S,et al. SFRP tumour suppressor genes are potential plasma-based epigenetic biomarkers for malignant pleural mesothelioma[J]. Disease Markers,2017,7(15):1-10.
• [25]MARSIT C J,MCCLEAN M D,FURNISS C S,et al.Epigenetic inactivation of the SFRP genes is associated with drinking,smoking and HPV in head and neck squamous cell carcinoma[J]. International Journal of Cancer,2016,119(8):1761-1766.

文章评论(Comment)：