切换至 "中华医学电子期刊资源库"

中华妇幼临床医学杂志(电子版) ›› 2016, Vol. 12 ›› Issue (06) : 660 -666. doi: 10.3877/cma.j.issn.1673-5250.2016.06.008

所属专题: 文献

论著

高迁移率族蛋白-1及Hepsin在宫颈癌组织中的表达与临床意义
程慧1, 张蓓1, 成杰1,(), 李妍雨1, 滕鹏1   
  1. 1. 221009江苏,徐州市中心医院妇产科
  • 收稿日期:2016-06-14 修回日期:2016-09-08 出版日期:2016-12-01
  • 通信作者: 成杰

Expression and clinical significance of high mobility group box-1 and Hepsin in cervical carcinoma tissues

Hui Cheng1, Bei Zhang1, Jie Cheng1,(), Yanyu Li1, Peng Teng1   

  1. 1. Department of Obstetrics and Gynecology, Xuzhou Central Hospital, Xuzhou 221009, Jiangsu Province, China
  • Received:2016-06-14 Revised:2016-09-08 Published:2016-12-01
  • Corresponding author: Jie Cheng
  • About author:
    Corresponding author: Cheng Jie, Email:
引用本文:

程慧, 张蓓, 成杰, 李妍雨, 滕鹏. 高迁移率族蛋白-1及Hepsin在宫颈癌组织中的表达与临床意义[J/OL]. 中华妇幼临床医学杂志(电子版), 2016, 12(06): 660-666.

Hui Cheng, Bei Zhang, Jie Cheng, Yanyu Li, Peng Teng. Expression and clinical significance of high mobility group box-1 and Hepsin in cervical carcinoma tissues[J/OL]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2016, 12(06): 660-666.

目的

探讨高迁移率族蛋白(HMGB)-1和Hepsin在宫颈癌中的表达与临床意义。

方法

选择2008年5月至2010年6月,在徐州市中心医院住院治疗的70例宫颈癌患者为研究对象。将所有患者手术切除的宫颈癌组织及癌旁2 cm处组织,分别纳入宫颈癌组及癌旁组,均为70例;并选取同期因宫颈良性病变于本院手术获取的20例良性病变宫颈组织,纳入对照组。采用免疫组织化学链霉菌抗生物素蛋白-过氧化物酶链结(SP)法检测上述3组组织中HMGB-1及Hepsin蛋白表达情况,并统计学分析其表达差异,不同临床因素下HMGB-1及Hepsin蛋白在宫颈癌组织中阳性表达率差异及此2种蛋白在宫颈癌组织中表达的相关性;并对2种蛋白不同阳性表达强度宫颈癌患者进行生存分析。本研究所有研究对象均签署知情同意书,并取得本院伦理道德委员会批准。

结果

①宫颈癌组HMGB-1及Hepsin蛋白阳性表达率,均分别较癌旁组或对照组高,而癌旁组此2种蛋白阳性表达率,均较对照组高,且差异均有统计学意义(P<0.05)。②免疫组织化学SP染色结果显示,良性病变宫颈组织中HMGB-1及Hepsin蛋白表达呈阴性,而宫颈癌癌旁组织中此2种蛋白呈淡黄色或黄色阳性(++)表达,宫颈癌组织中,则此2种蛋白呈棕褐色强阳性表达(+++),并且主要位于细胞质。③宫颈癌组的70例宫颈癌组织中,肿瘤浸润深度为T3+T4者及有淋巴结转移者的HMGB-1蛋白阳性表达率,较T1+T2者及无淋巴结转移者高,且差异均有统计学意义(P<0.05);而肿瘤分化程度为低分化者、肿瘤浸润深度为T3+T4者、有淋巴结转移者,以及肿瘤、淋巴结转移、远隔器官转移(TNM)分期为Ⅲ+Ⅳ期者的Hepsin蛋白阳性表达率,均较肿瘤分化程度为高/中分化者、肿瘤浸润深度为T1+T2者、无淋巴结转移者及肿瘤TNM分期为Ⅰ+Ⅱ期者高,且差异均有统计学意义(P<0.05)。④HMGB-1蛋白与Hepsin蛋白在宫颈癌组织中的表达呈正相关关系(r=15.27,P=0.01)。⑤影响宫颈癌患者5年生存结局的独立危险因素包括HMGB-1蛋白(+++)表达(HR=11.637,95%CI:4.351~38.213,P<0.05)及Hepsin蛋白(+++)表达(HR=10.142,95%CI:4.285~33.275,P<0.05)。

结论

HMGB-1及Hepsin蛋白的增强表达与宫颈癌侵袭性增强有关,其表达水平可作为评估宫颈癌患者预后的指标。

Objective

To explore expression and clinical significance of high mobility group box (HMGB)-1 and Hepsin in cervical carcinoma.

Methods

A total of 70 cases of cervical carcinoma patients from May 2008 to June 2010 in Xuzhou Central Hospital were selected as study subjects. Seventy cases of surgical ablated cervical carcinoma tissues and 70 cases of para-cancer tissues of 2 cm near to cancer, were included in cervical carcinoma group and para-cancer group; and 20 cases of benign lesion cervical tissues which were obtained from cervical tumor enucleation or adnexectomy because of benign cervical lesions in the same period in same hospital were selected as the control groups. The expression of HMGB-1 and Hepsin proteins in these 3 groups were detected by immunohistochemistry streptavidin-perosidase (SP) method.The differences of expression levels of HMGB-1 protein and Hepsin protein in 3 groups and the differences of positive expression rates of HMGB-1 and Hepsin proteins in cervical carcinoma tissue in different clinical factors were compared statistically.Analyzed the correlation between HMGB-1 protein and Hepsin protein expression level in cervical carcinoma tissue.And the survival analysis of cervical carcinoma patients with different expression intensities of 2 kinds of proteins were conducted. The study protocol was approved by the Ethical Review Board of Investigation in Human Being of Xuzhou Central Hospital.Informed consent was obtained from each participant.

Results

①The positive expression rates of HMGB-1 and Hepsin proteins in cervical carcinoma group were higher than those of para-cancer group and control group, respectively, also the positive expression rates of HMGB-1 and Hepsin proteins in para-cancer group were higher than those of control group, and the differences were statistically significant(P<0.05). ②Immunohistochemical SP staining results showed that the HMGB-1 and Hepsin proteins were negative expression in benign lesion cervical tissues, pale yellow or yellow particles of positive expression(+ + ) in cancer adjacent tissues, brown particles of positive expression(+ + + ) in cervical carcinoma tissues and mainly located in the cytoplasm.③In 70 cases cervical carcinoma tissues, the positive expression rates of HMGB-1 protein of patients with tumor invasion depth of T3+ T4 and lymph node metastasis were higher than that of patients with tumor invasion depth of T1+ T2 and without lymph node metastasis, and the differences were statistically significant(P<0.05); the positive expression rates of Hepsin protein of patients with low differentiation tumors, tumor invasion depth of T3+ T4, lymph node metastasis, and tumor, node, metastasis(TNM) stages of Ⅲ+ Ⅳ were higher than that of patients with high or middle differentiation tumors, tumor invasion depth of T1+ T2, without lymph node metastasis and tumor TNM stages of Ⅰ+ Ⅱ, and the differences were statistically significant(P<0.05). ④There was a positive correlation between HMGB-1 protein and Hepsin protein expression level in cervical carcinoma tissue (r=15.27, P=0.01). ⑤The risk factors of 5-year survival outcomes in cervical carcinoma patients including HMGB-1 protein (+ + + ) expression(HR=11.637, 95%CI: 4.351-38.213, P<0.05) and Hepsin protein (+ + + ) expression(HR=10.142, 95%CI: 4.285-33.275, P<0.05).

Conclusions

The over expression level of HMGB-1 and Hepsin proteins were related to the increased invasion of cervical carcinoma.The expression level of these 2 kinds of protein might act as indicators for the prognostic evaluation of cervical carcinoma patients.

表1 HMGB-1及Hepsin蛋白在宫颈癌组织、癌旁组织及良性病变宫颈组织中阳性表达率比较[例数(%)]
图1 HMGB-1及Hepsin蛋白在不同组织中的表达(图1A~1C:分别为HMGB-1蛋白在良性病变宫颈组织、宫颈癌旁组织及宫颈癌组织中的表达;图1D~1F:分别为Hepsin蛋白在良性病变宫颈组织、宫颈癌旁组织及宫颈癌组织中的表达)(SP染色,高倍)
表2 不同临床因素下HMGB-1及Hepsin蛋白在宫颈癌组织中阳性表达率比较[例数(%)]
表3 宫颈癌组HMGB-1及Hepsin蛋白不同阳性表达强度患者的生存情况分析
[1]
包颖,刘明,朱金福,等.液基细胞学和高危型HPV DNA检测在宫颈癌筛查中的相关性[J].中国实用医药,2012,7(18):60-61.
[2]
Tanimoto H,Yan Y,Clarke J,et al.Hepsin,a cell surface serine protease identified in hepatoma cells,is overexpressed in ovarian cancer[J].Cancer Res,1997,57(14):2884-2887.
[3]
吴英娟.宫颈癌组织中HMGB-1、PCNA的表达变化及临床意义[J].山东医药,2015,55(23):21-23.
[4]
李俊华,钟山,郭晖,等.肾脏缺血再灌注损伤过程中天然免疫分子高迁移率族蛋白B1释放变化[J].中华实验外科杂志,2010,27(12):1809-1811.
[5]
刘辉,姚咏明,丁丽华,等.活化T细胞核因子-2可介导高迁移率族蛋白B1促进白细胞介素-2转录表达[J].中华实验外科杂志,2010,27(10):1425-1428.
[6]
苏卫民,毕明宏.HMGB1/MMP9在非小细胞肺癌中的表达及临床意义[J].临床肺科杂志,2012,17(8):1463-1465.
[7]
张世栋,徐美林.HMGB1和NF-κB p65在非小细胞肺癌组织中的表达及意义[J].山东医药,2011,51(8):17-19.
[8]
程宝泉,李延青,李文捷,等.胰腺癌HMGB1表达及其与血行转移的关系研究[J].中华胰腺病杂志,2008,8(5):308-311.
[9]
贺小燕,王海琳,陈晓红,等.HMGB1在卵巢癌中的表达及临床意义[J].现代生物医学进展,2011,11(4):695-697.
[10]
Bandiera A, Bonifacio D, Manfioletti G, et al.Expression of HMGI(Y) proteins in squamous intraepithelial and invasive lesions of the uterine cervix[J].Cancer Res,1998,58(3):426-431.
[11]
付欣,杜晓琴,郝权.宫颈鳞癌组织高迁移率族蛋白HMGB1表达及其临床意义的研究[J].中华肿瘤防治杂志,2008,15(5):357-359.
[12]
Sheng X,Du X,Zhang X,et al.Clinical value of serum HMGB1 levels in early detection of recurrent squamous cell carcinoma of uterine cervix: comparison with serum SCCA,CYFRA21-1,and CEA levels[J]. Croat Med J,2009,50(5):455-464.
[13]
Mitola S, Belleri M, Urbinati C, et al.Cutting edge:extracellular high mobility group box-1 protein is a proangiogenic cytokine[J].J Immunol,2006,176(1):12-15.
[14]
徐姗,姚咏明,董宁,等.高迁移率族蛋白B1诱导的树突状细胞对T淋巴细胞增殖及功能性极化的影响[J].中华实验外科杂志,2008,25(1):42-44.
[15]
Yin M,Xu Y,Lou G,et al.LAPTM4B overexpression is a novel predictor of epithelial ovarian carcinoma metastasis[J].Int J Cancer,2011,129(3):629-635.
[16]
Goulet B,Chan G,Chambers AF,et al.An emerging role for the nuclear localization of maspin in the suppression of tumor progression and metastasis[J].Biochem Cell Biol,2012,90(1):22-38.
[17]
Alvarez SA, Darcy KM, Hutson A,et al. The regulation of MASPIN expression in epithelial ovarian cancer: association with p53 status, and MASPIN promoter methylation: a gynecologic oncology group study[J].Gynecol Oncol,2011,123(2): 314-319.
[18]
StephanC,YousefGM,ScorilasA,et al.Hepsin is highly over expressed in and a new candidate for a prognostic indicator in prostate cancer[J].J Urol, 2004,171(1):187-191.
[19]
Matsuo T, Nakamura K, Takamoto N, et al.Expression of the serine protease Hepsin and clinical outcome of human endometrial cancer[J].Anticancer Res,2008, 28(1A):159-164.
[20]
赵灵,蔡红兵,江大琼.高迁移率族蛋白B1和基质金属蛋白酶-9在宫颈鳞癌中的表达及其临床意义[J]. 武汉大学学报:医学版,2010,31(3):343-346.
[21]
Lipari MT, Li W, Moran P, et al.Furin-cleaved proprotein convertase subtilisin/kexin type 9 (PCSK9) is active and modulates low density lipoprotein receptor and serum cholesterol levels[J].J Biol Chem,2012,287(52):43482-43491.
[22]
Lucas JM,True L,Hawley S,et al.The androgen-regulated type Ⅱ serine protease TMPRSS2 is differentially expressed and mislocalized in prostate adenocarcinoma[J].J Pathol,2008,215(2):118-125.
[23]
Wilson S, Greer B, Hooper J,et al.The membrane-anchored serine protease, TMPRSS2, activates PAR-2 in prostate cancer cells[J].Biochem J,2005,388(Pt 3):967-972.
[24]
何鲜辉,齐玲,李馨蕊. HMGA1蛋白在宫颈癌及癌前病变中的表达与临床意义[J].中国妇幼保健,2013,28(17):2838-2839.
[25]
夏百荣,印明柱,葛婷婷,等.Hepsin在卵巢上皮癌组织中的表达及其与预后的关系[J].中国妇产科临床杂志,2013,14(2):143-147.
[1] 石皆春, 范子玉, 邢燕. 不同筛查方法预警宫颈原位腺癌的效能[J/OL]. 中华妇幼临床医学杂志(电子版), 2024, 20(05): 575-581.
[2] 张少华, 林爱齐, 张玉, 董晓云, 刘红英. HLAIL基因多态性及其与复发性自然流产的相关性[J/OL]. 中华妇幼临床医学杂志(电子版), 2024, 20(03): 251-259.
[3] 高伟聪, 李丽, 张中华, 朱向辉, 刘素巧. 宫颈癌患者糖调节受损对改良根治术后2年内复发的影响作用[J/OL]. 中华妇幼临床医学杂志(电子版), 2024, 20(02): 231-237.
[4] 李玉萍, 马会, 禹航. 腹腔镜下子宫动脉阻断术联合子宫肌瘤切除术治疗子宫肌瘤临床疗效[J/OL]. 中华妇幼临床医学杂志(电子版), 2024, 20(02): 238-244.
[5] 蒋冉, 邹彩艳, 桑谊荃. 宫颈上皮内瘤变Ⅲ患者血清性激素水平及其与高危型人乳头瘤病毒感染的关系[J/OL]. 中华妇幼临床医学杂志(电子版), 2023, 19(06): 683-688.
[6] 魏丽坤, 张旭红, 罗营, 薛凤霞, 王颖梅, 宋学茹, 田丽娜, 张艳芳, 王艳霞, 田文艳. 卵巢子宫内膜异位囊肿发生恶变并发盆腔脓肿1例并文献复习[J/OL]. 中华妇幼临床医学杂志(电子版), 2023, 19(06): 696-702.
[7] 武渊, 朱必清, 何丹, 王海蓉, 李倩. 采取调强放疗联合后装治疗宫颈癌患者的预后模型及危险分层系统构建[J/OL]. 中华妇幼临床医学杂志(电子版), 2023, 19(06): 734-744.
[8] 代雯荣, 赵丽娟, 李智慧. 细胞外囊泡对胚胎着床影响的研究进展[J/OL]. 中华妇幼临床医学杂志(电子版), 2023, 19(05): 616-620.
[9] 王璐, 樊杨. 子宫内膜癌相关生物标志物研究现状[J/OL]. 中华妇幼临床医学杂志(电子版), 2023, 19(05): 511-516.
[10] 张生军, 赵阿静, 李守博, 郝祥宏, 刘敏丽. 高糖通过HGF/c-met通路促进结直肠癌侵袭和迁移的实验研究[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(01): 21-24.
[11] 刘柏隆. 女性压力性尿失禁阶梯治疗之手术治疗方案选择[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2025, 19(01): 126-126.
[12] 刘柏隆, 周祥福. 女性尿失禁吊带手术并发症处理的经验分享[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2025, 19(01): 127-127.
[13] 李晓阳, 刘柏隆, 周祥福. 大数据及人工智能对女性盆底功能障碍性疾病的诊断及风险预测[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2023, 17(06): 549-552.
[14] 高红琴, 陈晨, 陆瑞科, 王小雨, 张敏, 李少华, 郝梨岚, 黄新程, 关凌耀, 张韵红. 外阴阴道假丝酵母菌病对女性阴道-宫颈菌群的影响研究[J/OL]. 中华临床医师杂志(电子版), 2023, 17(06): 720-725.
[15] 黎璞, 生秀杰. 妊娠合并子宫颈癌的管理[J/OL]. 中华产科急救电子杂志, 2024, 13(04): 202-208.
阅读次数
全文


摘要