[1]杜靖,李晨,王晓静,等.白细胞介素-2和信号转导和转录激活因子5在宫颈病变患者血清、宫颈组织和细胞中的表达及意义[J].新乡医学院学报,2022,39(10):934-941.[doi:10.7683/xxyxyxb.2022.10.007]
 DU Jing,LI Chen,WANG Xiaojing,et al.Expression and significance of interleukin-2 and signal transducer and activator of transcription 5 in serum,cervical tissues and cells of patients with cervical lesions[J].Journal of Xinxiang Medical University,2022,39(10):934-941.[doi:10.7683/xxyxyxb.2022.10.007]
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白细胞介素-2和信号转导和转录激活因子5在宫颈病变患者血清、宫颈组织和细胞中的表达及意义
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《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
39
期数:
2022年10
页码:
934-941
栏目:
临床研究
出版日期:
2022-10-05

文章信息/Info

Title:
Expression and significance of interleukin-2 and signal transducer and activator of transcription 5 in serum,cervical tissues and cells of patients with cervical lesions
作者:
杜靖1李晨2王晓静2李婉悦2樊凯2沙静3
(1.新疆医科大学基础医学院生理学教研室/新疆地方病分子生物学重点实验室,新疆 乌鲁木齐 830011;2.新疆医科大学基础医学院,新疆 乌鲁木齐 830011;3.新疆生产建设兵团医院,新疆 乌鲁木齐 830000)
Author(s):
DU Jing1LI Chen2WANG Xiaojing2LI Wanyue2FAN Kai2SHA Jing3
(1.Department of Physiology,College of Basic Medicine,Xinjiang Medical University,Xinjiang Key Laboratory of Molecular Biology of Endemic Diseases,Urumqi 830011,Xinjiang Uygur Autonomous Region,China;2.Basic Medical College of Xinjiang Medical University,Urumqi 830011,Xinjiang Uygur Autonomous Region,China;3.Hospital of Xinjiang Production and Construction Corps,Urumqi 830000,Xinjiang Uygur Autonomous Region,China)
关键词:
人乳头瘤病毒宫颈病变白细胞介素-2白细胞介素-2受体信号转导和转录激活因子5
Keywords:
human papilloma viruscervical lesionsinterleukin-2interleukin-2 receptorsignal transducer and activator of transcription 5
分类号:
R737.33
DOI:
10.7683/xxyxyxb.2022.10.007
文献标志码:
A
摘要:
目的 探讨白细胞介素-2(IL-2)、IL-2受体(IL-2R)和信号转导和转录激活因子5(STAT5)在宫颈病变患者血清、宫颈组织和细胞中的表达变化及其与宫颈病变严重程度的关系。方法 选择2020年6月至2021年6月新疆生产建设兵团医院门诊或住院治疗的25例宫颈鳞状细胞癌患者(宫颈鳞状细胞癌组)、40例慢性宫颈炎患者(慢性宫颈炎组)和50例体检健康女性(健康对照组)为研究对象,应用荧光定量聚合酶链反应(PCR)法检测3组受试者人乳头瘤病毒(HPV)16/18感染情况,酶联免疫吸附试验法检测3组受试者血清和宫颈脱落细胞中IL-2水平,实时荧光定量PCR法检测3组受试者宫颈脱落细胞中IL-2、IL-2R、STAT5a和STAT5b mRNA水平。另外,收集新疆医科大学第一附属医院和新疆生产建设兵团医院病理科石蜡包埋的慢性宫颈炎组织35例和宫颈鳞状细胞癌组织87例(高分化30例,中分化42例,低分化15例),免疫组织化学法检测慢性宫颈炎和宫颈鳞状细胞癌组织中IL-2、IL-2R、STAT5和磷酸化STAT5(p-STAT5)蛋白的表达。结果 慢性宫颈炎组和宫颈鳞状细胞癌组患者HPV16/18阳性率高于健康对照组(χ2=6.762、13.868,P<0.05);宫颈鳞状细胞癌组患者HPV16/18阳性率显著高于慢性宫颈炎组(χ2=7.870,P<0.05)。慢性宫颈炎组和宫颈鳞状细胞癌组HPV16/18阳性患者血清和宫颈脱落细胞中IL-2水平低于健康对照组,宫颈鳞状细胞癌组HPV16/18阳性患者血清和宫颈脱落细胞中IL-2水平低于慢性宫颈炎组(P<0.05);慢性宫颈炎组和宫颈鳞状细胞癌组HPV16/18阴性患者血清和宫颈脱落细胞中IL-2水平低于健康对照组,宫颈鳞状细胞癌组HPV16/18阴性患者血清和宫颈脱落细胞中IL-2水平低于慢性宫颈炎组(P<0.05);3组HPV16/18阳性受试者血清和宫颈脱落细胞中IL-2水平低于HPV16/18阴性受试者(P<0.05)。HPV16/18阳性受试者宫颈脱落细胞中与血清中IL-2水平呈正相关(r=0.665,P<0.05)。慢性宫颈炎组和宫颈鳞状细胞癌组患者宫颈脱落细胞中IL-2、IL-2R、STAT5a和STAT5b mRNA相对表达量低于健康对照组,宫颈鳞状细胞癌组患者宫颈脱落细胞中IL-2、IL-2R、STAT5a和STAT5b mRNA相对表达量低于慢性宫颈炎组(P<0.05)。宫颈鳞状细胞癌宫颈组织中IL-2、IL-2R阳性表达率显著低于慢性宫颈炎组织,STAT5和p-STAT5阳性表达率显著高于慢性宫颈炎组织(P<0.05)。高分化型宫颈鳞状细胞癌宫颈组织中IL-2、IL-2R阳性表达率显著高于中分化型和低分化型,STAT5和p-STAT5阳性表达率低于中分化型和低分化型(P<0.05);中分化型宫颈鳞状细胞癌宫颈组织中IL-2、IL-2R阳性表达率显著高于低分化型,STAT5和p-STAT5阳性表达率低于低分化型(P<0.05)。结论 HPV16/18阳性者血清和宫颈脱落细胞中IL-2水平低于HPV16/18阴性者,且随宫颈病变程度加重而降低;宫颈病变组织和细胞中IL-2和IL-2R表达随宫颈病变分化程度加重而降低,IL-2可能通过JAK/STAT通路激活STAT家族蛋白STAT5a、STAT5b参与宫颈癌的发生、发展;宫颈脱落细胞和血清IL-2联合检测可预测宫颈病变的进展。
Abstract:
Objective To investigate the expression of interleukin-2 (IL-2),IL-2 receptor (IL-2R) and signal transducer and activator of transcription 5(STAT5) in serum,cervical lesion tissues and cells of patients with cervical lesions and their relationship with the severity of cervical lesions.Methods Twenty-five patients with cervical squamous cell carcinoma (cervical squamous cell carcinoma group),40 patients with chronic cervicitis (chronic cervicitis group) and 50 healthy women (healthy control group) in hospitalization or outpatient program of Hospital of Xinjiang Production and Construction Corps from June 2020 to June 2021 were selected as the research objects;the human papillomavirus (HPV) 16/18 infection of subjects in the three groups was detected by fluorescence quantitative polymerase chain reaction (PCR),the IL-2 level in serum and cervical exfoliated cells of subjects in the three groups was detected by enzyme-linked immunosorbent assay,the levels of IL-2,IL-2R,STAT5A and STAT5b mRNA in cervical exfoliated cells of subjects in the three groups were detected by real-time fluorescence quantitative PCR.A total of 35 cases of chronic cervicitis tissues and 87 cases of cervical squamous cell carcinoma tissues (30 cases of well differentiated,42 cases of moderately differentiated and 15 cases of poorly differentiated) were collected from the First Affiliated Hospital of Xinjiang Medical University and Hospital of Xinjiang Production and Construction Corps,and the expressions of IL-2,IL-2R,STAT5 and phosphorylated STAT5(p-STAT5) in chronic cervicitis tissue and cervical squamous cell carcinoma tissue were detected by immunohistochemistry.Results The positive rate of HPV16/18 in patients in the chronic cervicitis group and cervical squamous cell carcinoma group was significantly higher than that in the healthy control group (χ2=6.762,13.868;P<0.05);the positive rate of HPV16/18 in patients in the cervical squamous cell carcinoma group was significantly higher than that in the chronic cervicitis group(χ2= 7.870,P<0.05).The level of IL-2 in serum and cervical exfoliated cells of HPV16/18 positive patients in the chronic cervicitis group and cervical squamous cell carcinoma group was significantly lower than that in the healthy control group,the level of IL-2 in the serum and cervical exfoliated cells of HPV16/18 positive patients in the cervical squamous cell carcinoma group was significantly lower than that in the chronic cervicitis group (P<0.05);the level of IL-2 in serum and cervical excrete cells of HPV16/18 negative patients in the chronic cervicitis group and cervical squamous cell carcinoma group was significantly lower than that in the healthy control group,the level of IL-2 in serum and cervical exfoliated cells of HPV16/18 negative patients in the cervical squamous cell carcinoma group was significantly lower than that in the chronic cervicitis group (P<0.05);the level of IL-2 in serum and cervical exfoliated cells of HPV16/18 positive subjects was significantly lower than that of HPV16/18 positive subjects in the three groups (P<0.05);there was a positive correlation between cervical exfoliated cells and serum IL-2 level in HPV16/18 positive subjects (r=0.665,P<0.05).The relative expressions of IL-2,IL-2R,STAT5a and STAT5b mRNA in cervical exfoliated cells of patients in the chronic cervicitis group and cervical squamous cell carcinoma group were significantly lower than those in the healthy control group,the relative expressions of IL-2,IL-2R,STAT5a and STAT5b mRNA in cervical exfoliated cells of patients in the cervical squamous cell carcinoma group were significantly lower than those in the chronic cervicitis group(P<0.05).The positive expression rates of IL-2 and IL-2R in cervical squamous cell carcinoma tissues were significantly lower than those in the chronic cervicitis tissues,and the positive expression rates of STAT5 and p-STAT5 were significantly higher than those in the chronic cervicitis tissues (P<0.05).The positive expression rates of IL-2 and IL-2R in well-differentiated cervical squamous cell carcinoma were significantly higher than those in moderately differentiated and poorly differentiated cervical squamous cell carcinoma,while the positive expression rates of STAT5 and p-STAT5 were significantly lower than those in moderately differentiated and poorly differentiated cervical squamous cell carcinoma (P<0.05);the positive expression rates of IL-2 and IL-2R in moderately differentiated cervical squamous cell carcinoma were significantly higher than those in poorly differentiated cervical squamous cell carcinoma,and the positive expression rates of STAT5 and p-STAT5 were significantly lower than those in poorly differentiated cervical squamous cell carcinoma (P<0.05).Conclusion The levels of IL-2 in serum and cervical exfoliated cells of HPV16/18 positive patients are lower than that of HPV16/18 positive patients,and those decrease with the severity of cervical lesions;and the expressions of IL-2 and IL-2R in tissues and cells of cervical lesions decrease with the aggravation of differentiation of cervical lesions.IL-2 may participate in the occurrence and development of cervical cancer by activating the STAT5A and STAT5b through JAK/STAT pathway;the combined detection of IL-2 in cervical exfoliated cells and serum can predict the progression of cervical lesions.

参考文献/References:

[1]  BRAY F,FERLAY J,SOERJOMATARAMI,et al.Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].CA Cancer J Clin,2018,68(6):394-424.
[2] GUO M,XU J,DU J.Trends in cervical cancer mortality in China from 1989 to 2018:an age-period-cohort study and Joinpoint analysis[J].BMC Public Health,2021,21(1):1329.
[3] LU X,JIANG L,ZHANG L,et al.Immune signature-based subtypes of cervical squamous cell carcinoma tightly associated with human papillomavirus type 16 expression,molecular features,and clinical outcome[J].Neoplasia,2019,21(6):591-601.
[4] ZHOU C F,MA J,HUANG L,et al.Cervical squamous cell carcinoma-secreted exosomal miR-221-3p promotes lymphangiogenesis and lymphatic metastasis by targeting VASH1[J].Oncogene,2019,38(8):1256-1268.
[5] SHA J,DU J,YANG J,et al.Changes of serum levels of tumor necrosis factor(TNF-α)and soluble interleukin-2 receptor(SIL-2R)in patients with cervical cancer and their clinical significance[J].Am J Transl Res,2021,13(6):6599-6604.
[6] MORGAN" E L,MACDONALD A.JAK2 inhibition impairs proliferation and sensitises cervical cancer cells to cisplatin-induced cell death[J].Cancers (Basel),2019,11(12):1934.
[7] VINK M A,BOGAARDS J A,VANKEMENADE F J,et al.Clinical progression of high-grade cervical intraepithelial neoplasia:estimating the time to preclinical cervical cancer from doubly censored national registry data[J].Am J Epidemiol,2013,178(7):1161-1169.
[8] FILLON M.Immune checkpoint inhibitors may be safe for patients with preexisting autoimmune disease[J].CA Cancer J Clin,2020,70(1):3-4.
[9] YE S,SUN X,KANG B,et al.The kinetic profile and clinical implication of SCC-Ag in squamous cervical cancer patients undergoing radical hysterectomy using the Simoa assay:a prospective observational study[J].BMC Cancer,2020,20(1):138.
[10] 周兰,冯兰兰.阴道镜联合TCT检查用于宫颈癌机会性筛查价值研究[J].中国继续医学教育,2021,13(32):147-151.
ZHOU L,FENG L L.Clinicalvalue study of colposcopy plus TCT in oppo rtunistic screening for cervical cancer[J].China Continuing Med Educ,2021,13(32):147-151.
[11] VOLKOVA L V,PASHOV A I,OMELCHUK N N.Cervical carcinoma:oncobiology and biomarkers[J].Int J Mol Sci,2021,22(22):12571.
[12] SHARMA A,RAJAPPA M,SATYAM A,et al.Cytokines (TH1 and TH2) in patients with advanced cervical cancer undergoing neoadjuvant chemoradiation:correlation with treatment response[J].Int J Gynecol Cancer,2009,19(7):1269-1275.
[13] 沈丽,薛平莉,朱燕娜.HPV 感染及其基因型与宫颈病变患者病灶微环境 Th1/Th2平衡及疾病进展的关系[J].中华医院感染学杂志,2022,32(16):2510-2514.
SHEN L,XUEP L,ZHU Y N.Relations hip between HPV infection and its genotypes and Th1/Th2 balance and disease progression in lesionmicro-environment of patients with cervical lesions[J].Chin J Nosocomiol,2022,32(16):2510-2514.
[14] 韩钦,郭红燕,耿力.宫颈癌机会性筛查人群中高危型 HPV 感染状况及其与宫颈病变关系的研究[J].实用妇产科杂志,2018,34(3):194-197.
HAN Q,GUO H Y,GENG L.Relationship between high-risk HPV infection and cervical lsesions in cervical cancer opportunistic screening[J].J Pract Obstetr Gynecol,2018,34(3):194-197.
[15] PAPPA K I,LYGIROU V,KONTOSTATHI G,et al.Proteomic analysis of normal and cancer cervical cell lines reveals deregulation of cytoskeleton-associated proteins[J].Cancer Genomics Proteomics,2017,14(4):253-266.
[16] 吴帆.IL-2、IL-10、TGF-β1及其受体在宫颈癌及CIN患者宫颈鳞柱交界上皮中的表达[D].武汉:同济大学,2007.
WU F.The expression ofinterleukin-2,interleukin-10,transforming growthfactor-β1 and itsreceptor in squamouscolumnar junction epithelia of patients with cervical cancer or cervical intraepithelial neoplasia[D].Wuhan:Tongji University,2007.
[17] HEMNDEZ-MONTES" J,ROCHA-ZAVALLETA L,MONROY-GARCA A,et al.Peripheral blood lymphocytes from low-grade squamous intraepithelial lesions patients recognize vaccine antigens in the presence of activated dendritic cells,and produced high levels of CD8+ IFNγ+ T cells and low levels of IL-2 when induced to proliferate[J].Infect Agent Cancer,2012,7(1):12.
[18] ZHENG J J,MIAO J R,WU Q,et al.Correlation between HPV-negative cervical lesions and cervical microenvironment[J].Taiwan J Obstet Gynecol,2020,59(6):855-861.
[19] PETRINI C G,BASTOS L B,DUARTE G,et al.Downregulation of IL-2 and IL-23 in cervical biopsies of cervical intraepithelial lesions:across-sectional study[J].Acta Cytol,2020,64(5):442-451.
[20] LI B,ZHANG L,ZHAO J,et al.The value of cytokine levels in triage and risk prediction for women with persistent high-risk human papilloma virus infection of the cervix[J].Infect Agent Cancer,2019,14:16.
[21] ZHENG J J,SONG J H,YU C X,et al.Difference in vaginal microecology,local immunity and HPV infection among childbearing-age women with different degrees of cervical lesions in Inner Mongolia[J].BMC Womens Health,2019,19(1):109.
[22] HONG S,LAIMINS L A.The JAK-STAT transcriptional regulator,STAT-5,activates the ATM DNA damage pathway to induce HPV 31 genome amplification upon epithelial differentiation[J].PLoS Pathog,2013,9(4):e1003295.
[23] 吴思,吴盈盈,于淼,等.宫颈组织中Stat5b表达与宫颈病变的关系[J].中国医科大学学报,2019,48(2):144-148.
WU S,WU Y Y,YU M,et al.Relationship between Stat5b expression in cervical tissues and lesions[J].J China Med Univ,2019,48(2):144-148.
[24] CAL V,MIGLIAVACCA M,BAZAN V,et al.STAT proteins:from normal control of cellular events to tumorigenesis[J].J Cell Physiol,2003,197(2):157-168.
[25] AARONSON D S,HORVATH C M.A road map for those who don′t know JAK-STAT[J].Science,2002,296(5573):1653-1655.
[26] VAN BOXEL-DEZAIRE A H,RANI M R,STARK G R.Complex modulation of cell type-specific signaling in response to type I interferons[J].Immunity,2006,25(3):361-372.
[27] ZHANG Q,WANG H Y,LIU X,et al.STAT5A is epigenetically silenced by the tyrosine kinase NPM1-ALK and acts as a tumor suppressor by reciprocally inhibiting NPM1-ALK expression[J].Nat Med,2007,13(11):1341-1348.
[28] HWA V.STAT5B deficiency:impacts on human growth and immunity[J].Growth Horm IGF Res,2016,28:16-20.
[29] VALLE-MENDIOLA A,GUTIRREZ-HOYA A,LAGUNAS-CRUZ MDEL C,et al.Pleiotropic effects of IL-2 on cancer:its role in cervical cancer[J].Mediators Inflamm,2016,2016:2849523.
[30] MORGAN E L,MACDONALD A.Manipulation of JAK/STAT signalling by high-risk HPVs:potential therapeutic targets for HPV-associated malignancies[J].Viruses,2020,12(9):977.

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更新日期/Last Update: 2022-10-05