[1]仲亚东,孔德桐,马伯敏.甲状腺癌患者组织及手术前后血清中NR3C2 和ZEB1 表达水平及其与预后价值研究[J].现代检验医学杂志,2023,38(04):94-99.[doi:10.3969/j.issn.1671-7414.2023.04.017]
 ZHONG Yadong,KONG Detong,MA Bomin.Study on the Expression Level of NR3C2 and ZEB1 in Thyroid Cancer Tissue and Serum of Patients before and after Surgery and Their Prognostic Value[J].Journal of Modern Laboratory Medicine,2023,38(04):94-99.[doi:10.3969/j.issn.1671-7414.2023.04.017]
点击复制

甲状腺癌患者组织及手术前后血清中NR3C2 和ZEB1 表达水平及其与预后价值研究()
分享到:

《现代检验医学杂志》[ISSN:/CN:]

卷:
第38卷
期数:
2023年04期
页码:
94-99
栏目:
论著
出版日期:
2023-07-15

文章信息/Info

Title:
Study on the Expression Level of NR3C2 and ZEB1 in Thyroid Cancer Tissue and Serum of Patients before and after Surgery and Their Prognostic Value
文章编号:
1671-7414(2023)04-094-06
作者:
仲亚东1孔德桐2马伯敏3
(1. 邹城市人民医院乳甲血管疝外科,山东济宁 273500;2. 泗水县人民医院普外科,山东济宁 273200;3. 鱼台县人民医院肿瘤科,山东济宁 272300)
Author(s):
ZHONG Yadong1KONG Detong2MA Bomin3
(1.Breast Nail Vascular Hernia Surgery,Zoucheng People’s Hospital,Shandong Jining 273500,China; 2.Department of General Surgery, Sishui County People’s Hospital,Shandong Jining 273200, China; 3.Department of Tumor, Yutai County People’s Hospital,Shandong Jining 272300, China)
关键词:
甲状腺癌核受体亚家族3C 组成员2E 盒结合锌指蛋白1
分类号:
R736.1;R730.43
DOI:
10.3969/j.issn.1671-7414.2023.04.017
文献标志码:
A
摘要:
目的 探讨核受体亚家族3C 组成员2(nuclear receptor subfamily 3, group C, member 2,NR3C2)和E 盒结合锌指蛋白1(E-box-binding zinc finger protein 1,ZEB1)在甲状腺癌组织中的表达差异及手术前后血清NR3C2 mRNA 和ZEB1 mRNA 的相对表达水平,分析其与患者预后的关系。方法 选取2018 年3 月~ 2019 年5 月在邹城市人民医院进行手术治疗的85 例甲状腺癌患者的癌组织和癌旁组织(距癌组织>3cm)样本,采用免疫组织化学法(ICC)检测癌组织和癌旁组织中NR3C2 和ZEB1 的表达;分别收集甲状腺癌患者(实验组)手术前、术后1 周、术后1 个月的血清样本,以及同期到该院体检的30 例健康者(对照组)的血清样本,采用实时荧光定量PCR 检测NR3C2 mRNA 和ZEB1mRNA 相对表达水平;分析NR3C2 mRNA 和ZEB1 mRNA 相对表达水平与临床病理特征的关系;术前NR3C2 和ZEB1表达水平与甲状腺癌患者三年生存率的关系用Kaplan-Meier 法分析,采用对数秩检验进行组间生存曲线差异分析;采用多因素COX 回归分析甲状腺癌患者预后影响因素。结果 免疫组织化学法观察显示,癌组织中NR3C2 阳性表达率(36.47%)低于癌旁组织(72.94%),癌组织中ZEB1 阳性表达率(67.06%)高于癌旁组织(30.59%),差异具有统计学意义(χ2=22.814,22.624,均P<0.001);实验组术前血清NR3C2 mRNA 表达水平(0.55±0.14)低于对照组表达水平(0.97±0.22),术前、术后1 周和术后1 个月血清NR3C2 mRNA 表达水平(0.55±0.14,0.69±0.15,0.89±0.19)依次升高,差异具有统计学意义(t=12.038,F=95.217,P<0.001);实验组术前ZEB1 mRNA 表达水平(1.88±0.28)高于对照组表达水平(1.02±0.41),术前、术后1 周、术后1 个月血清ZEB1 mRNA 表达水平(1.88±0.28, 1.43±0.32,1.15±0.29)依次降低,差异具有统计学意义(t=12.716,F=130.564,P<0.001);甲状腺癌患者血清NR3C2 mRNA 表达和ZEB1mRNA 表达水平与TNM 分期、淋巴结转移、分化程度和包膜浸润有关(t=2.449,2.081,3.938,2.212;2.013,2.348,2.029,2.096,均P<0.05);NR3C2 mRNA 高表达组三年生存率(86.00%)显著高于低表达组(40.00%),ZEB1 mRNA 高表达组三年生存率(35.29%)显著低于低表达组(88.24%),差异均有统计学意义(χ2=4.168,5.593,均P<0.05);多因素COX 回归分析显示,TNM 分期、淋巴结转移、包膜浸润、NR3C2 mRNA 和ZEB1 mRNA 均为甲状腺癌患者预后影响因素(P < 0.05)。结论 甲状腺癌组织和血清中NR3C2 表达下调,ZEB1 表达上调,NR3C2 和ZEB1 表达水平影响患者预后生存率,对甲状腺癌患者预后评估具有重要意义。
Abstract:
Objective To investigate the expression of nuclear receptor subfamily 3, group C, member 2 (NR3C2) and E-boxbinding zinc finger protein 1 (ZEB1) in thyroid cancer tissues, compare the relative expression of NR3C2 mRNA and ZEB1 mRNA in serum before and after surgery, and analyze their relationship with patient prognosis. Methods From March 2018 to May 2019, samples of cancer tissue and paracancerous tissue (>3cm from the cancer tissue) of 85 patients with thyroid cancer who underwent surgery in Zoucheng People’s Hospital were collected. Immunohistochemistry(ICC)was used to detect the expression of NR3C2 and ZEB1 in cancer tissue and paracancerous tissue. Serum samples were collected from thyroid cancer patients (experimental group) before surgery, 1 week after surgery, and 1 month after surgery, and serum samples from 30 healthy people (control group) who went to the hospital for physical examination were also collected, real-time PCR was applied to detect the relative expression of NR3C2 mRNA and ZEB1 mRNA. The clinicopathological characteristics of patients with thyroid cancer were collected, and the relationship between the relative expression levels of NR3C2 mRNA and ZEB1 mRNA and the clinicopathological characteristics was analyzed. Kaplan-Meier method was applied to analyze the relationship between preoperative NR3C2 and ZEB1 expression levels and 3-year survival in patients with thyroid cancer, log-rank test was used to analyze the difference of survival curves between groups, and multivariate COX regression was used to analyze prognostic factors in thyroid cancer patients. Results ICC observation showed that the positive expression rate of NR3C2 in cancer tissue (36.47%) was lower than that in adjacent tissue (72.94%), and the positive expression rate of ZEB1 in cancer tissue (67.06%) was higher than that in adjacent tissue (30.59%),and the differences were statistically significant (χ2=22.814, 22.624, all P<0.001). The preoperative serum NR3C2 mRNA in the experimental group (0.55±0.14) was lower than that in the control group (0.97±0.22), the relative expression levels of serum NR3C2 mRNA increased in sequence before surgery, 1 week after surgery, and 1 month after surgery (0.55±0.14, 0.69±0.15, 0.89±0.19) ,and the differences were statistically significant (t=12.038, F=95.217, P<0.001). The expression level of ZEB1 mRNA in the experimental group before operation (1.88±0.28) was higher than that in the control group(1.02±0.41), and the relative expression level of serum ZEB1 mRNA decreased in sequence before operation, 1 week after operation, and 1 month after operation (1.88±0.28, 1.43±0.32, 1.15±0.29) ,and the differences was statistically significant (t=12.716,F=130.564, P<0.001). The relative expression of serum NR3C2 mRNA and ZEB1 RNA in patients with thyroid cancer was related to TNM stage, lymph node metastasis, degree of differentiation, and capsule invasion (t=2.449, 2.081, 3.938, 2.212; 2.013, 2.348, 2.029, 2.096, all P<0.05). The 3-year survival rate of NR3C2 mRNA high expression group (86.00%) was obviously higher than that of low expression group (40.00%), and the 3-year survival rate of ZEB1 mRNA high expression group (35.29%) was obviously lower than that of low expression group (88.24%), the differences were statistically significant (χ2=4.168, 5.593, all P<0.05). Multivariate COX regression analysis showed that TNM stage, lymph node metastasis, capsular invasion, NR3C2 mRNA, and ZEB1 mRNA were all prognostic factors in patients with thyroid cancer (P<0.05). Conclusion The expression of NR3C2 in thyroid cancer tissue and serum was down-regulated, and the expression of ZEB1 was up-regulated,the expression levels of NR3C2 and ZEB1 affect the prognosis and survival rate of patients, and are of great significance for the prognosis evaluation of patients with thyroid cancer.

参考文献/References:

[1] 赵芳芳, 郭红, 陈嘉. LncRNA TUG1 在甲状腺癌组织中的表达及其对细胞增殖和迁移的影响[J]. 现代检验医学杂志, 2020, 35(6): 42-47. ZHAO Fangfang, GUO Hong, CHEN Jia. Expression of LncRNA TUG1 in thyroid carcinoma tissues and its effect on cell proliferation and migration[J]. Journal of Modern Laboratory Medicine, 2020, 35(6): 42-47.
[2] 李玉平, 王伦善. 血清TSH,TPOAb 和TGAb 水平在良恶性甲状腺结节中的鉴别诊断价值[J]. 现代检验医学杂志, 2019, 34(5): 93-97. LI Yuping, WANG Lunshan. Diagnostic value of thyroid autoantibodies and tsh in thyroid nodules[J]. Journal of Modern Laboratory Medicine, 2019, 34(5):93-97.
[3] 赵白信, 于慧娟, 焦方杰, 等. 彩色多普勒超声联合血清glactin-3,HMGB-1 和TSGF 水平检测在甲状腺腺瘤诊断中的临床意义[J]. 现代检验医学杂志,2021, 36(4): 87-92. ZHAO Baixin, YU Huijuan, JIAO Fangjie, et al. Clinical significance of color doppler ultrasound combined with serum glactin-3, HMGB-1 and TSGF levels in the diagnosis of thyroid adenoma[J]. Journal of Modern Laboratory Medicine, 2021, 36(4): 87-92.
[4] FAN Yaohua, LI Yan, ZHU Yuzhang, et al. MiR-301b-3p regulates breast cancer cell proliferation, migration, and invasion by targeting NR3C2[J].Journal of Oncology, 2021, 2021: 8810517.
[5] ZHAO Zhijian, ZHANG Mengping, DUAN Xiaolu, et al. Low NR3C2 levels correlate with aggressive features and poor prognosis in non-distant metastatic clear-cell renal cell carcinoma[J]. Journal of Cellular Physiology, 2018, 233(10): 6825-6838.
[6] ZHANG Zhengliang, CHE Xiangming, YANG Ni, et al. MiR-135b-5p promotes migration, invasion and EMT of pancreatic cancer cells by targeting NR3C2[J]. Biomedicine & Pharmacotherapy, 2017, 96: 1341-1348.
[7] KIM E J, KIM J S, LEE S, et al. ZEB1-regulated lnc-Nr2f1 promotes the migration and invasion of lung adenocarcinoma cells[J]. Cancer Letters, 2022, 533:215601.
[8] 张倩, 段婷婷, 任玉宝. 结直肠癌组织中PLOD2,ZEB1 表达变化及意义[J]. 山东医药, 2022, 62(10):67-70. ZHANG Qian, DUAN Tingting, REN Yubao. Changes and significance of PLOD2 and ZEB1 expression in colorectal cancer[J]. Shandong Medical Journal, 2022, 62(10): 67-70.
[9] 刘建宇, 薛栋, 高立科. 锌指E 盒结合蛋白1 在恶性肿瘤中的研究进展[J]. 中国现代普通外科进展,2022, 25(5): 377-380. LIU Jianyu, XUE Dong, GAO Like. Research progress of Zinc finger E-box binding protein 1 in malignant tumors[J]. Chinese Journal of Current Advances in General Surgery, 2022, 25(5): 377-380.
[10] 王玲, 王健, 赵寅生, 等. 甲状腺乳头状癌患者血清促甲状腺激素水平和组织促甲状腺激素受体检测的临床应用价值[J]. 现代检验医学杂志, 2021, 36(1):61-64. WANG Ling, WANG Jian, ZHAO Yinsheng, et al. Clinical application value of serum thyrotropin level and tissue thyrotropin receptor detection in patients with thyroid papillary carcinoma[J]. Journal of Modern Laboratory Medicine, 2021, 36(1): 61-64.
[11] 宋创业, 严丽, 孟艳林, 等. 甲状腺癌发生发展及预后的相关影响因素[J]. 中华普通外科学文献(电子版), 2020, 14(1): 72-75. SONG Chuangye, YAN Li, MENG Yanlin, et al. Related factors of occurrence, development and prognosis of thyroid cancer[J]. Chinese Archives of General Surgery(Electronic Edition), 2020, 14(1): 72-75.
[12] PRETE A, DE SOUZA P B, CENSI S, et al. Update on fundamental mechanisms of thyroid cancer[J]. Frontiers in Endocrinology, 2020, 11:102.
[13] WANG Chao, HU Fengyun. Long noncoding RNA SOX2OT silencing alleviates cerebral ischemiareperfusion injury via miR-135a-5p-mediated NR3C2 inhibition[J]. Brain Res Bull, 2021, 173:193-202.
[14] GUO Jingyu, WANG Yukun, L? Bo, et al. MiR-454 performs tumor-promoting effects in oral squamous cell carcinoma via reducing NR3C2[J]. Journal of Oral Pathology & Medicine, 2020, 49(4): 286-293.
[15] YUAN Fan, YUAN Ruixue, REN Decheng, et al. A novel NR3C2 polymorphism and the increased thyroidstimulating hormone concentration are associated with venlafaxine treatment outcome in Chinese Han MDD patients[J]. Psychiatry Research, 2020, 284: 112690.
[16] 卢达新, 高艳霞, 于丽凤, 等. 微小RNA hsa-mir-301b 对乳腺癌细胞增殖能力的影响研究[J]. 中国实用内科杂志, 2021, 41(2): 141-145. LU Daxin, GAO Yanxia, YU Lifeng, et al. Effect of microRNA hsa-mir-301b on proliferation of breast cancer cells[J]. Chinese Journal of Practical Internal Medicine, 2021, 41(2): 141-145.
[17] 陈恩更, 陈力, 曹高扬, 等. 基于免疫基因组学的结肠腺癌患者预后风险模型的建立[J]. 解放军医学杂志, 2020, 45(9): 935-939. CHEN Engeng, CHEN Li, CAO Gaoyang, et al. Construction of prognostic risk model for patients with colon adenocarcinoma based on immunogenomics analysis[J]. Medical Journal of Chinese People’s Liberation Army, 2020, 45(9): 935-939.
[18] 柳家荣, 张琪. ZEB1 基因在甲状腺乳头状癌诊断中的意义及对细胞上皮- 间质转化的影响[J]. 实用癌症杂志, 2022, 37(8): 1224-1228. LIU Jiarong, ZHANG Qi. Significance of ZEB1 gene in diagnosis and differentiation of papillary thyroid carcinoma and its influence on cell epithelialmesenchymal transition[J]. The Practical Journal of Cancer, 2022, 37(8): 1224-1228.
[19] 钟淙, 石琴, 章超. LncRNA MALAT1 调控miR-144-3p/ZEB1 对肺癌放射敏感性的影响[J]. 实用肿瘤杂志, 2022, 37(4): 307-314. ZHONG Cong, SHI Qin, ZHANG Chao. Effect of LncRNA MALAT1 regulating miR-144-3p/ZEB1 on radiosensitivity of lung cancer[J]. Journal of Practical Oncology, 2022, 37(4): 307-314.
[20] 张道宝, 徐建国. MiR-200 家族及侵袭相关基因ZEB1, ZEB2 和CTNNB1 在颅咽管瘤组织中的表达及意义[J]. 临床神经外科杂志, 2022, 19(2): 167-170. ZHANG Daobao, XU Jianguo. Expression and significance of miR-200 family and invasion-related genes ZEB1,ZEB2 and CTNB1 in craniopharyngioma[J]. Journal of Clinical Neurosurgery, 2022, 19(2): 167-170.
[21] 黄丽群, 谢龙, 张冠杰, 等. 白藜芦醇下调E 盒结合锌指蛋白1 表达对甲状腺癌细胞侵袭、迁移的影响[J]. 中国临床药理学杂志, 2021, 37(15): 2035-2038. HUANG Liqun, XIE Long, ZHANG Guanjie, et al. Effects of resveratrol on the invasion and migration of thyroid cancer cells by down regulating the expression of E-box binding Zinc finger protein 1[J]. The Chinese Journal of Clinical Pharmacology, 2021, 37(15): 2035-2038.

相似文献/References:

[1]彭继英a,杨红杰b,石晓欣a,等.细针穿刺细胞学检查在甲状腺癌碘-131 治疗后复发诊断中的应用价值[J].现代检验医学杂志,2020,35(01):127.[doi:10.3969/j.issn.1671-7414.2020.01.033]
 PENG Ji-yinga,YANG Hong-jieb,SHI Xiao-xina,et al.Application Value of Fine Needle Aspiration Cytology in Recurrence Diagnosis of Thyroid Cancer after Iodine-131 Treatment[J].Journal of Modern Laboratory Medicine,2020,35(04):127.[doi:10.3969/j.issn.1671-7414.2020.01.033]
[2]赵芳芳,郭 红,陈 嘉.LncRNA TUG1 在甲状腺癌组织中的表达及其对细胞增殖和迁移的影响[J].现代检验医学杂志,2020,35(06):42.[doi:doi:10.3969/j.issn.1671-7414.2020.06.011]
 ZHAO Fang-fang,GUO Hong,CHEN Jia.Expression of LncRNA TUG1 in Thyroid Carcinoma Tissues and Its Effect onCell Proliferation and Migration[J].Journal of Modern Laboratory Medicine,2020,35(04):42.[doi:doi:10.3969/j.issn.1671-7414.2020.06.011]
[3]谈玖婷,傅聿明,刘 婧,等.甲状腺癌组织中DCBLD2 和MAP4K3 的表达及与临床病理特征及预后的关系[J].现代检验医学杂志,2024,39(02):34.[doi:10.3969/j.issn.1671-7414.2024.02.007]
 TAN Jiuting,FU Yuming,LIU Jing,et al.Expression of DCBLD2 and MAP4K3 in Thyroid Cancer Tissue and Their Relationship with Clinico-pathological Features and Prognosis[J].Journal of Modern Laboratory Medicine,2024,39(04):34.[doi:10.3969/j.issn.1671-7414.2024.02.007]
[4]张廷华a,胡友元b,袁 博.miR-100-5p 对甲状腺癌细胞增殖与凋亡调控作用的实验研究[J].现代检验医学杂志,2024,39(04):56.[doi:10.3969/j.issn.1671-7414.2024.04.011]
 ZHANG Tinghuaa,HU Youyuanb,YUAN Bo.Experimental Study on the Regulatory Effects of miR-100-5p on Proliferation and Apoptosis of Thyroid Cancer Cells[J].Journal of Modern Laboratory Medicine,2024,39(04):56.[doi:10.3969/j.issn.1671-7414.2024.04.011]

备注/Memo

备注/Memo:
作者简介:仲亚东(1980-),男,本科,主治医师,研究方向:甲状腺相关临床研究,E-mail:Zyad0402@163.com。
通讯作者:马伯敏(1982-),E-mail:mabomin521@163.com。
更新日期/Last Update: 2023-07-15