白细胞介素-17A与雌激素受体α和β在上皮性卵巢癌组织中的表达及其临床意义

doi:10.3969/j.issn.1004-616x.2024.01.007

癌变·畸变·突变 ›› 2024, Vol. 36 ›› Issue (1): 42-47.doi: 10.3969/j.issn.1004-616x.2024.01.007

白细胞介素-17A与雌激素受体α和β在上皮性卵巢癌组织中的表达及其临床意义

王科芳¹, 陈瑜², 吴陈雨¹, 刘梅¹, 汪丽杰¹, 田建广¹, 周小会¹, 许岚³

1. 华东疗养院妇科, 江苏无锡 214065;
2. 无锡市妇幼保健院妇科, 江苏无锡 214002;
3. 无锡市人民医院妇科, 江苏无锡 214023

收稿日期:2023-09-02 修回日期:2023-12-21 出版日期:2024-02-19 发布日期:2024-02-19
通讯作者: 周小会
作者简介:王科芳,E-mail:p235345@163.com。
基金资助:
无锡市科技发展资金项目（N20202006）

Clinicopathological roles of IL-17A and estrogen receptors α, β in epithelial ovarian cancer

WANG Kefang¹, CHEN Yu², WU Chenyu¹, LIU Mei¹, WANG Lijie¹, TIAN Jianguang¹, ZHOU Xiaohui¹, XU Lan³

1. Department of Gynecology, Huadong Sanatorium, Wuxi 214065;
2. Department of Gynecology, Wuxi Maternal and Child Health Hospital, Wuxi 214002;
3. Department of Gynecology, Wuxi People's Hospital, Wuxi 214023, Jiangsu, China

Received:2023-09-02 Revised:2023-12-21 Online:2024-02-19 Published:2024-02-19

摘要/Abstract

摘要： 目的：探讨白细胞介素（IL）-17A与雌激素受体α（ERα）、ERβ在上皮性卵巢癌（EOC）组织中的表达水平及其与患者临床病理特征和预后的关系。方法：回顾性分析2018年8月—2022年8月间在无锡市妇幼保健院诊治的102例EOC患者的临床和病理资料，采用实时荧光定量PCR（qPCR）检测癌组织及相应病旁组织中IL-17A、ERα、ERβ mRNA的表达情况，计算ERα/β比值。分析IL-17A mRNA、ERα/β与患者临床病理特征的关系，并采用Kaplan-Meier法和Cox回归法分析IL-17A mRNA、ERα/β对EOC患者预后总生存期（OS）的影响。结果：与癌旁组织比较，癌组织中IL-17A、ERα m RNA表达水平及ERα/β水平均升高（P<0.05），而ERβ mRNA表达水平降低（P<0.05）。分别以IL-17A mRNA、ERα/β的平均值0.52、3.85为分界值进行高、低表达分组，结果显示IL-17A高表达及ERα/β高比值与FIGO分期、淋巴结转移、腹水量有关（P<0.05）。随访时间12~60个月，中位随访时间36个月，随访期间共38例（37.25%）患者死亡。Kaplan-Meier分析显示，IL-17A mRNA高表达者累积生存率低于其低表达者（P<0.05）；ERα/β高比值者累积生存率亦低于ERα/β低比值者（P<0.05）。多因素Cox分析显示，FIGO III+IV期、术后残灶>2 cm、IL-17A m RNA高表达、ERα/β高比值是EOC患者总体生存期的独立危险因素（P<0.05）。结论：EOC组织中IL-17A、ERα及ERα/β mRNA上调，而ERβ m RNA水平下调，且IL-17A高表达及ERα/β高比值的EOC患者预后相对较差。

关键词: 上皮性卵巢癌, 白细胞介素-17A, 雌激素受体α, 雌激素受体β, 临床病理特征, 预后

Abstract: OBJECTIVE: To investigate expression levels of interleukin(IL)-17A and estrogen receptor α(ERα) and ERβ in epithelial ovarian cancer(EOC) tissues and their relationship with clinicopathological features and prognosis. METHODS: Clinical and pathological data of 102 EOC patients admitted to Wuxi Maternal and Child Health Hospital during August 2018-August 2022 were retrospectively analyzed. IL-17A, ERα, and ERβ mRNA expressions in cancer tissues and paracellular tissues were detected by real-time fluorescence quantitative PCR(qPCR), and the ERα/β ratio was calculated. The relationships between IL-17A m RNA, ERα/β and clinicopathological features were analyzed. Effects of IL-17A m RNA, ERα/β on the prognostic overall survival of EOC were analyzed by the Kaplan-Meier method and Cox regression analysis.RESULTS: Expressions of IL-17A, ERα and ERα/β were higher in the cancer than the paracancer tissues, while the expression of ERβ was decreased(P<0.05). The high and low expression groups of IL-17A and ERα/βwere divided by the mean values of 0.52 and 3.85, respectively, and the results showed that high IL-17A expression and high ERα/β ratio were associated with FIGO stage, lymph node metastasis, and the amount of ascites(P<0.05). The follow-up period ranged from 12 to 60 months, with a median follow-up period of 36 months, and a total of 38 cases(37.25%) died during the follow-up period. Kaplan Meier analysis showed that the cumulative survival rate of those with high IL-17A mRNA expression was lower than that of those with low expression(P<0.05), and the cumulative survival rate of those with high ERα/β ratio was lower than that of those with low ERα/β ratio(P<0.05). Multifactorial Cox analysis showed that FIGO stage III + IV, postoperative residual foci >2 cm, high expression of IL-17A mRNA, and high ERα/β ratio were independent risk factors for overall survival in patients with EOC(P<0.05). CONCLUSION: IL-17A, ERα and ERα/βwere up-regulated while the ERβ mRNA level was down-regulated in EOC, and the prognosis of EOC patients with high IL-17A expression and high ERα/β ratio was poor.

Key words: epithelial ovarian cancer, interleukin-17A, estrogen receptor α, estrogen receptor β, clinicopathological features, prognosis

中图分类号:

R737.31

王科芳, 陈瑜, 吴陈雨, 刘梅, 汪丽杰, 田建广, 周小会, 许岚. 白细胞介素-17A与雌激素受体α和β在上皮性卵巢癌组织中的表达及其临床意义[J]. 癌变·畸变·突变, 2024, 36(1): 42-47.

WANG Kefang, CHEN Yu, WU Chenyu, LIU Mei, WANG Lijie, TIAN Jianguang, ZHOU Xiaohui, XU Lan. Clinicopathological roles of IL-17A and estrogen receptors α, β in epithelial ovarian cancer[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2024, 36(1): 42-47.

参考文献

[1] ARMSTRONG D K, ALVAREZ R D, BAKKUM-GAMEZ J N,et al. Ovarian cancer, version 2.2020, NCCN clinical practice guidelines in oncology[J]. J Natl Compr Canc Netw, 2021, 19(2):191-226.
[2] 黄海涛,陈姝玉,耿旭,等. 2005—2016年中国女性卵巢癌发病及死亡趋势研究[J].中国全科医学, 2022, 25(8):990-994.
[3] XU X L, HUANG Z Y, YU K, et al. Estrogen biosynthesis and signal transduction in ovarian disease[J]. Front Endocrinol:Lausanne, 2022, 13:827032.
[4] NEGI A, KESARI K K, VOISIN-CHIRET A S. Estrogen receptor-α targeting:PROTACs, SNIPERs, peptide-PROTACs,antibody conjugated PROTACs and SNIPERs[J]. Pharmaceutics,2022, 14(11):2523.
[5] LIU M M, ZHANG Y N, XU Q Q, et al. Apigenin inhibits the histamine-induced proliferation of ovarian cancer cells by downregulating ERα/ERβ expression[J]. Front Oncol, 2021,11:682917.
[6] CHENG R, XUE X O, LIU X L. Expression of IL17A in endometrial carcinoma and effects of IL17A on biological behaviour in Ishikawa cells[J]. J Int Med Res, 2020, 48(9):300060520950563.
[7] 朱熠,张国楠.卵巢癌、输卵管癌和腹膜癌FIGO2013分期和临床意义的解读[J].肿瘤预防与治疗, 2015, 28(5):291-294.
[8] SCHOUTROP E, MOYANO-GALCERAN L, LHEUREUX S,et al. Molecular, cellular and systemic aspects of epithelial ovarian cancer and its tumor microenvironment[J]. Semin Cancer Biol, 2022, 86(Pt 3):207-223.
[9] BANERJEE A, CAI S R, XIE G Z, et al. A novel estrogen receptor β agonist diminishes ovarian cancer stem cells via suppressing the epithelial-to-mesenchymal transition[J].Cancers, 2022, 14(9):2311.
[10] WU H M, ZENG L H, OU J X, et al. Estrogen acts through estrogen receptor-β to promote mannan-induced psoriasis-like skin inflammation[J]. Front Immunol, 2022, 13:818173.
[11] YU C Y, NIU X L, DU Y R, et al. Correction to:IL-17A promotes fatty acid uptake through the IL-17A/IL-17RA/p-STAT3/FABP4 axis to fuel ovarian cancer growth in an adipocyte-rich microenvironment[J]. Cancer Immunol Immunother, 2023, 72(8):2875-2877.
[12] GUO N, ZHANG J W. Interleukin-17 promotes the development of ovarian cancer through upregulation of MTA1expression[J]. Am J Cancer Res, 2022, 12(12):5646-5656.
[13] 刘长慧,金百灵.宫颈癌合并阴道炎患者病原菌感染情况及Th17细胞和血清细胞因子的变化[J].中国病原生物学杂志,2021, 16(7):837-840.
[14] POPOVIĆ M, DEDIĆ PLAVETIĆ N, VRBANEC D, et al.Interleukin 17 in early invasive breast cancer[J]. Front Oncol,2023, 13:1171254.
[15] KANG S P, WU Q L, YANG B Y, et al. Estrogen enhanced the expression of IL-17 by tissue-resident memory γδT cells from uterus via interferon regulatory factor 4[J]. FASEB J, 2022, 36(2):e22166.
[16] SHUAI C, YANG X M, PAN H M, et al. Estrogen receptor downregulates expression of PD-1/PD-L1 and infiltration of CD8+T cells by inhibiting IL-17 signaling transduction in breast cancer[J]. Front Oncol, 2020, 10:582863.
[17] ALI E T, MASRI M A M, SIDDIG E E, et al.Immunohistochemical expression of interleukin-17 and hormonal receptors in benign and malignant breast lesions[J]. BMC Res Notes, 2020, 13(1):300.
[18] SPAŁKOWSKA M, DYDUCH G, BRONIATOWSKA E, et al.Molecular proof of a clinical concept:expression of estrogen alpha-, beta-receptors and G protein-coupled estrogen receptor 1(GPER)in histologically assessed common nevi,dysplastic nevi and melanomas[J]. Medicina, 2021, 57(11):1228.
[19] MA Y F, CHEN C, LI D Q, et al. Targeting of interleukin(IL)-17A inhibits PDL1 expression in tumor cells and induces anticancer immunity in an estrogen receptor-negative murine model of breast cancer[J]. Oncotarget, 2017, 8(5):7614-7624.
[20] TSAI Y F, HUANG C C, LIN Y S, et al. Interleukin 17A promotes cell migration, enhances anoikis resistance, and creates a microenvironment suitable for triple negative breast cancer tumor metastasis[J]. Cancer Immunol Immunother,2021, 70(8):2339-2351.
[21] LI S, NA R S, LI X H, et al. Targeting interleukin-17 enhances tumor response to immune checkpoint inhibitors in colorectal cancer[J]. Biochim Biophys Acta Rev Cancer, 2022, 1877(4):188758.
[22] TAKANO E A, YOUNES M M, MEEHAN K, et al. Estrogen receptor beta expression in triple negative breast cancers is not associated with recurrence or survival[J]. BMC Cancer, 2023, 23(1):459.
[23] CASTELLANOS M R, FANOUS E, THAKER R, et al.Expression patterns and clinical significance of estrogen receptor in non-small cell lung cancer[J]. Pathol Res Pract,2023, 241:154298.
[24] KUMAR V, CHAUHAN S S. Daidzein induces intrinsic pathway of apoptosis along with ER α/β ratio alteration and ROS production[J]. Asian Pac J Cancer Prev, 2021, 22(2):603-610.
[25] CHAKRABORTY B, BYEMERWA J, KREBS T, et al.Estrogen receptor signaling in the immune system[J]. Endocr Rev, 2023, 44(1):117-141.

白细胞介素-17A与雌激素受体α和β在上皮性卵巢癌组织中的表达及其临床意义

Clinicopathological roles of IL-17A and estrogen receptors α, β in epithelial ovarian cancer

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	薛松, 胡加海, 董祥宁. PGAM5在胰腺癌中的表达及其与临床病理指标的关系[J]. 癌变·畸变·突变, 2024, 36(1): 29-34.
[2]	朱文标, 丘波, 谢寿城, 肖焕钦, 刘高敏. 跨膜蛋白79在肝细胞癌中的表达及临床意义[J]. 癌变·畸变·突变, 2023, 35(6): 426-430.
[3]	许金花, 李静静, 吴国峰, 任亚俊, 王雪, 张骞云. 非小细胞肺癌患者血清miR-146a与TNF-α、Treg的相关性及其对预后判断的价值[J]. 癌变·畸变·突变, 2023, 35(6): 462-466.
[4]	杨上英, 黄明翔, 许德新, 刘加夫, 陈新富. DNAJB4与非小细胞肺癌免疫细胞浸润和患者预后的相关性分析[J]. 癌变·畸变·突变, 2023, 35(6): 467-472.
[5]	高榴, 禹莉. 线粒体转录因子A在肿瘤发生发展中作用的研究进展[J]. 癌变·畸变·突变, 2023, 35(6): 485-488.
[6]	呙文静, 邓慧, 宋萍, 张孟贤. 转化生长因子β诱导蛋白在胶质瘤中的表达及生物学功能[J]. 癌变·畸变·突变, 2023, 35(5): 341-348.
[7]	韦来凤, 洪超群, 陈柳伊, 许镒洧, 伍方财. 实验室炎症相关指标的列线图对预测舌鳞状细胞癌患者手术预后的价值[J]. 癌变·畸变·突变, 2023, 35(5): 366-373.
[8]	杨程晴, 崔永辉, 郑紫恒. 结肠癌患者血清中miR-653-5p的表达及其临床意义[J]. 癌变·畸变·突变, 2023, 35(4): 261-265.
[9]	覃熙媛, 朱莹, 李伟滔, 郑晓玲, 梁远秋. 上皮性卵巢癌组织中FoxM1的表达及其临床意义[J]. 癌变·畸变·突变, 2023, 35(4): 273-278.
[10]	刘瑞雪, 张力为. 腺苷酸活化蛋白激酶在哈萨克族食管鳞癌组织中的表达及意义[J]. 癌变·畸变·突变, 2023, 35(4): 285-291.
[11]	刘颖, 王蕊, 郭晓, 董律吏, 张艳, 赵银环, 杜芸. 肺腺癌胸腔积液DNA倍体异常与EGFR突变的关系及其对患者预后的影响[J]. 癌变·畸变·突变, 2023, 35(3): 178-182,186.
[12]	王平, 王华勇, 王浩, 雷大军. 骨肉瘤患者血清外泌体中miR-193a和miR-21-5p表达水平及其临床意义[J]. 癌变·畸变·突变, 2023, 35(3): 197-201.
[13]	黄利丹, 吴月明, 王亚帝, 谭琦. EGFR突变型肺腺癌组织中VEGF-A蛋白的表达及其临床意义[J]. 癌变·畸变·突变, 2023, 35(2): 116-120.
[14]	谭健华, 赖姚圳, 唐丽华, 周莉. 2种不同疗法对晚期上皮性卵巢癌的疗效及患者预后影响因素分析[J]. 癌变·畸变·突变, 2023, 35(2): 131-138.
[15]	胡学义, 沈丰, 武伦, 苏才武, 魏涧. SPON2在甲状腺乳头状癌中的表达及其临床意义[J]. 癌变·畸变·突变, 2023, 35(1): 9-14.