[1]张亚军a,刘裴丽b,江 月a,等.子宫内膜癌组织中 dMMR 蛋白和miRNA Let-7 表达水平及临床价值的研究[J].现代检验医学杂志,2024,39(03):48-52+108.[doi:10.3969/j.issn.1671-7414.2024.03.008]
　ZHANG Yajuna,LIU Peilib,JIANG Yuea,et al.Expression Level and Clinical Value of dMMR Proteins and miRNA Let-7 in Endometrial Carcinoma Tissue[J].Journal of Modern Laboratory Medicine,2024,39(03):48-52+108.[doi:10.3969/j.issn.1671-7414.2024.03.008]
点击复制

子宫内膜癌组织中 dMMR 蛋白和miRNA Let-7 表达水平及临床价值的研究()
分享到：

《现代检验医学杂志》[ISSN:/CN:]

卷:
第39卷
期数:
2024年03期
页码:
48-52+108
栏目:
论著
出版日期:
2024-05-15

文章信息/Info

Title:
Expression Level and Clinical Value of dMMR Proteins and miRNA Let-7 in Endometrial Carcinoma Tissue
文章编号:
1671-7414（2024）03-048-06
作者:
张亚军a; 刘裴丽b; 江 月a; 闫 莉a; 陈云云a; 蒋 欣a; 孟凡菲b
（连云港市妇幼保健院 a 病理科；b 妇科，江苏连云港 222000）
Author(s):
ZHANG Yajuna; LIU Peilib; JIANG Yuea; YAN Lia; CHEN Yunyuna; JIANG Xina; MENG Fanfeib
(a．Department of Pathology；b．Department of Gynecology，Lianyungang Maternal and Child Health Hospital, Jiangsu Lianyungang 222000, China)
关键词:
子宫内膜癌; 林奇综合征; DNA 错配修复蛋白; 微小RNA Let-7
分类号:
R737.33；R730.43
DOI:
10.3969/j.issn.1671-7414.2024.03.008
文献标志码:
A
摘要:
目的 探讨子宫内膜癌（endometrial carcinoma，EC）中微小RNA Let-7（miRNA Let-7）表达水平与DNA 错配修复（DNA mismatch repair，dMMR）蛋白表达缺失的关系及意义。方法 选取2016 年5 月～ 2022 年12 月在江苏省连云港市妇幼保健院行根治性手术切除的子宫内膜癌患者74 例，分别用免疫组织化学法检测 dMMR 蛋白（包括MLH1，PMS2，MSH2，MSH6）的表达、实时荧光定量聚合酶链反应（qRT-PCR）检测miRNA Let-7 的相对表达量，按照 dMMR 蛋白表达情况，将EC 患者分为表达完整组（n=43）和表达缺失组（n=31），采用Logistic 多因素回归分析与dMMR 蛋白缺失相关的危险因素、绘制受试者工作特征（receiver operating characteristic，ROC）曲线评估相关因素的预测价值。结果 74 例EC 病例中，miRNA Let-7 的表达水平在肌层浸润＜ 1/2 组显著高于肌层浸润≥ 1/2 组，差异具有统计学意义（t=1.79，P=0.04）；dMMR 蛋白表达的缺失率为41.89%，且年龄＜ 55 岁组和miRNA Let-7 低表达组（＜ 0.715）患者中的 dMMR 蛋白缺失率高于≥ 55 岁组和miRNA Let-7 高表达组（≥ 0.715），差异具有统计学意义（χ2=3.92，4.50，均P ＜ 0.05）；Logistic 多因素回归分析结果显示miRNA Let-7 表达水平是发生 dMMR 表达缺失的独立危险因素（P=0.012）；Spearman 相关分析表明，miRNA Let-7 的表达水平与 dMMR 蛋白缺失呈明显负相关（r=-0.247，P=0.034）；ROC 曲线分析结果显示，miRNA Let-7 表达水平对于预测EC 患者中发生 dMMR 蛋白的缺失具有一定的价值，其AUC为0.737，最佳临界值为0.77，敏感度和特异度分别为0.651，0.806。结论 子宫内膜癌患者中miRNA Let-7 的表达水平与 dMMR 蛋白缺失具有相关性，也是发生 dMMR 蛋白缺失的危险因素，有望为预测 dMMR 的表达缺失提供帮助。
Abstract:
Objective To investigate the relationship between the expression level of miRNA Let-7 and the deletion of DNA mismatch repair (dMMR) proteins in endometrial carcinoma (EC). Methods A total of 74 patients with EC who underwent radical surgery at Lianyungang Maternal and Child Health Hospital in Jiangsu Province from May 2016 to December 2022 were selected. Immunohistochemistry was used to detect the expression of dMMR proteins (including MLH1, PMS2, MSH2, and MSH6), while real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was performed to measure the relative expression levelof miRNA Let-7. According to the expression of dMMR proteins, EC patients were divided into the complete expression group（n=43） and the absent expression group（n=31）. Logistic multivariate regression analysis was conducted to identify risk factors associated with dMMR protein deficiency, and receiver operating characteristic (ROC) curve was plotted to evaluate the predictive value of relevant factors. Results In 74 cases of EC, the expression level of miRNA Let-7 was higher in the myographic infiltration < 1/2 group than in the myographic infiltration ≥1/2 group, and the difference was significant (t=1.79, P=0.04). The deletion rate of dMMR protein expression was 41.89%, the deletion rate in patients aged < 55 years and miRNA Let-7 low expression group（＜ 0.715） were higher than those in ≥ 55 years and miRNA Let-7 high expression group（≥ 0.715）, with significant differences (χ2=3.92，4.50，all P<0.05). Logistic regression analysis revealed that miRNA Let-7 expression level was an independent risk factor for dMMR expression deletion (P=0.012). Spearman correlation analysis demonstrated a negative correlation between miRNA Let-7 expression level and dMMR protein deletion (r=-0.247, P=0.034). ROC curve analysis indicated that the expression level of miRNA Let-7 had a certain predictive value for dMMR protein deletion in EC patients, with an AUC of 0.737, an optimal critical value of 0.77, a sensitivity and a specificity of 0.651 and 0.806，respectively. Conclusion The expression level of miRNA Let-7 was correlated with the deletion of dMMR proteins in patients diagnosed with EC. Moreover, it served as a potential risk factor for dMMR protein deficiency. It may offer valuable insights into predicting dMMR expression deletion.

参考文献/References:

[1] MORAK M, IBISLER A, KELLER G, et al . Comprehensive analysis of the MLH1 promoter region in 480 patients with colorectal cancer and 1150 controls reveals new variants including one with a heritable constitutional MLH1 epimutation [J]. Journal of Medical Genetics, 2018, 55(4): 240-248.
[2] 马珂, 杨曦, 杨子慧, 等. 子宫内膜癌相关林奇综合征筛查方法的研究[J]. 实用妇产科杂志, 2023,39(1): 51-55. MA Ke, YANG Xi, YANG Zihui, et al. Study of screening methods for Lynch syndrome in patients with endometrial carcinoma [J]. Journal of Practical Obstetrics and Gynecology, 2023, 39(1): 51-55.
[3] 章艳斐, 盛慧超, 楼善贤, 等. 子宫内膜癌患者人表皮生长因子受体2 错配修复蛋白的表达及预后分析[J]. 中国妇幼保健, 2023, 38(14): 2668-2671. ZHANG Yanfei, SHENG Huichao, LOU Shanxian,et al. Expression and prognosis analysis of human epidermal growth factor receptor 2, mismatch repair protein in patients with endometrial carcinoma[J].Maternal and Child Health Care of China, 2023, 38(14):2668-2671.
[4] 杨凤泊, 赵丽君, 徐游贵, 等. 子宫内膜癌组织错配修复基因MMR 表达及其临床意义[J]. 现代妇产科进展, 2020, 29(2)：120-124, 129. YANG Fengbo, ZHAO Lijun, XU Yougui, et al. Expression and clinical significance of mismatch repair gene MMR in endometrial carcinoma [J]. Progress in Obstetrics and Gynecology, 2020, 29(2): 120-124, 129.
[5] BERNSTEIN D L, JIANG Xinpei, ROM S. Let-7 microRNAs：their role in cerebral and cardiovascular diseases, inflammation, cancer, and their regulation[J].Biomedicines, 2021, 9(6): 606.
[6] GILLES M E, SLACK F J. Let-7 microRNA as a potential therapeutic target with implications for immunotherapy[J]. Expert Opinion on Therapeutic Targets, 2018, 22(11): 929-939.
[7] 齐丽宁, 张红真, 魏旭静, 等. 子宫内膜癌组织中miR-10a 及Let-7i 的表达及临床意义[J]. 肿瘤代谢与营养电子杂志, 2019, 6(1): 75-78. QI Lining, ZHANG Hongzhen, WEI Xujing, et al. Expression and clinical significance of miR-10a and let-7i in endometrial carcinoma [J]. Electronic Journal of Metabolism and Nutrition of Cancer, 2019, 6(1): 75-78.
[8] 王英英, 朱娇. 三阴性乳腺癌患者血清miR-146a,miR let-7a 水平表达与临床病理特征和化疗疗效的相关性研究[J]. 现代检验医学杂志, 2021, 36(6): 60-63. WANG Yingying, ZHU Jiao. Correlation of serum miR-146a and miR let-7a expression with clinicopathological characteristics and chemotherapy efficacy in patients with triple negative breast cancer [J].Journal of Modern Laboratory Medicine, 2021, 36(6):60-63.
[9] 毛兴波, 盛涛, 庄丽萍, 等. 胰腺癌组织miRNA let-7a 与HMGA2 的表达及血清miRNA let-7a 水平对胰腺癌的诊断价值[J]. 四川大学学报(医学版）, 2020,51(4): 540-545. MAO Xingbo, SHENG Tao, ZHUANG Liping, et al. Expression of miRNA let-7a and HMGA2 and diagnostic value of serum miRNA let-7a level in pancreatic cancer[J]. Journal of Sichuan University(Medical Science), 2020, 51(4): 540-545.
[10] 陈映含. 糖尿病肾脏病患者血清Let-7d mRNA 的相对表达量与肾功能进展的相关性研究[J]. 现代检验医学杂志, 2022, 37(1): 77-81. CHEN Yinghan. Study on the correlation between relative expression of serum Let-7d mRNA and renal function progression in patients with diabetic nephropathy[J].Journal of Modern Laboratory Medicine, 2022, 37(1): 77-81.
[11] KAHN R M, GORDHANDAS S, MADDY B P, et al. Universal endometrial cancer tumor typing:how much has immunohistochemistry, microsatellite instability,and MLH1 methylation improved the diagnosis of Lynch syndrome across the population?[J]. Cancer,2019, 125(18): 3172-3183.
[12] SALIMINEJAD K, KHORRAM KHORSHID H R, SOLEYMANI FARD S, et al. An overview of microRNAs: biology, functions, therapeutics, and analysis methods[J]. Journal of Cellular Physiology,2019, 234(5): 5451-5465.
[13] MORIDIKIA A, MIRZAEI H, SAHEBKAR A, et al. MicroRNAs: potential candidates for diagnosis and treatment of colorectal cancer [J]. Journal of Cellular Physiology, 2018, 233(2): 901-913.
[14] LU Nanhang, WEI Chuanyuan, QI Fazhi, et al. Hsa-let-7b suppresses cell proliferation by targeting UHRF1 in melanoma[J]. Cancer Investigation, 2020, 38(1): 52-60.
[15] TANG Huan, MA Meng, DAI Jie, et al. MiR-let-7b and miR-let-7c suppress tumourigenesis of human mucosal melanoma and enhance the sensitivity to chemotherapy[J]. Journal of Experimental & Clinical Cancer Research, 2019, 38(1): 212.
[16] LIU Yujie, HU Xing, HU Liang, et al. Let-7i-5p enhances cell proliferation, migration and invasion of ccRCC by targeting HABP4[J]. BMC Urology, 2021,21(1): 49.
[17] 邹震海, 程琪, 李中, 等. MiR-let-7g-3p 靶向HMGB2 调控膀胱癌细胞的增殖、迁移、侵袭和凋亡[J]. 南方医科大学学报, 2022, 42(9): 1335-1343. ZOU Zhenhai, CHENG Qi, LI Zhong, et al. MicroRNA let-7g-3p regulates proliferation, migration, invasion and apoptosis of bladder cancer cells by targeting HMGB2 [J]. Journal of Southern Medical University,2022, 42(9): 1335-1343.
[18] 龙玲艳, 王晴, 张蓓. MiR-let-7b, IMP3, HMGA2 在宫颈鳞癌中的表达及临床意义[J]. 临床与病理杂志,2022, 42(3): 539-546. LONG Lingyan, WANG Qing, ZHANG Bei. Expression and clinical significance of miR-let-7b, IMP3, and HMGA2 in cervical squamous cell carcinoma [J].Journal of Clinical and Pathological Research, 2022, 42(3): 539-546.
[19] 董玉科, 李玉杰, 黄炜, 等. 喉癌组织中Let-7a 表达及其临床意义[J]. 实用癌症杂志, 2023, 38(7): 1055-1057. DONG Yuke, LI Yujie, HUANG Wei, et al. Expression of Let-7a in laryngeal carcinoma and its clinical significance[J]. Practical Journal of Cancer, 2023,38(7): 1055-1057.
[20] ZHAO Shuangshuang, CHEN Lingli, ZANG Yuqin,et al. Endometrial cancer in Lynch syndrome[J].International Journal of Cancer, 2022, 150(1): 7-17.
[21] 高显华, 张卫, 刘连杰, 等. 林奇综合征的筛查策略和综合应用[J]. 中华胃肠外科杂志, 2019, 22(7):684-688. GAO Xianhua, ZHANG Wei, LIU Lianjie, et al. Comprehensive application of various screening strategies of Lynch syndrome[J]. Chinese Journal of Gastrointestinal Surgery, 2019, 22(7): 684-688.
[22] 慕庆玲, 夏宝国, 刘莹, 等.MMR 蛋白在Lynch 综合征相关子宫内膜癌初筛中的应用[J]. 现代妇产科进展, 2019, 28(7): 495-497. MU Qingling,XIA Baoguo,LIU Ying,et al. Application of MMR protein in primary screening of Lynch syndrome-related endometrial carcinoma[J]. Progress in Obstetrics and Gynecology, 2019, 28(7): 495-497.
[23] 郄智萍. 周洁, 庄晓丹，等.MMR 蛋白表达结合林奇综合征肿瘤家族史在林奇综合征相关子宫内膜癌筛查中的临床应用[J]. 中国现代医药杂志, 2022,24(09): 1-5. QIE Zhiping, ZHOU Jie, ZHUANG Xiaodan, et al. Clinical application of MMR protein expression combined with Lynch syndrome tumor family history in Lynch syndrome associated endometrial cancer screening[J]. Modern Medicine Journal of China, 2022,24(9): 1-5.

相似文献/References:

[1]李 玲a,罗雅文a,何 霞a,等.子宫内膜癌患者BMI与血清HE4,CA125联合检测的诊断价值[J].现代检验医学杂志,2018,33(05):91.[doi:10.3969/j.issn.1671-7414.2018.05.024]
　LI Linga,LUO Ya-wena,HE Xiaa,et al.Diagnostic Value of Combined Detection of Body Mass Index and Serum HE4,CA125 in Patients with Endometrial Carcinoma[J].Journal of Modern Laboratory Medicine,2018,33(03):91.[doi:10.3969/j.issn.1671-7414.2018.05.024]
[2]李晓丽,胡陇娟.子宫内膜癌组织中长链非编码RNA ZEB1-AS1的表达与临床特征及对化疗药物耐药性研究[J].现代检验医学杂志,2019,34(04):35.[doi:10.3969/j.issn.1671-7414.2019.04.009]
　LI Xiao-li,HU Long-juan.Research on Expression and Clinical Characteristics of Long-Chain Non-Coding RNA ZEB1-AS1 in Endometrial Carcinoma and Resistance to Chemotherapy Drugs[J].Journal of Modern Laboratory Medicine,2019,34(03):35.[doi:10.3969/j.issn.1671-7414.2019.04.009]
[3]王娟,刘鑫,席稳燕.HMMR-AS1 在子宫内膜癌化疗耐药中的作用[J].现代检验医学杂志,2020,35(05):45.[doi:10.3969/j.issn.1671-7414.2020.05.012]
　WANG Juan,LIU Xin,XI Wen-yan.Effect of HMMR-AS1 on the Chemotherapy-Resistance of Endometrial Cancer[J].Journal of Modern Laboratory Medicine,2020,35(03):45.[doi:10.3969/j.issn.1671-7414.2020.05.012]
[4]李功娟,张治洋,樊阳阳.FEZF1-AS1在子宫内膜癌中的表达及其与患者临床特征的相关性[J].现代检验医学杂志,2021,36(01):77.[doi:10.3969/j.issn.1671-7414.2021.01.020]
　LI Gong-juan,ZHANG Zhi-yang,FAN Yang-yang.Expression of FEZF1-AS1 in Endometrial Carcinoma and Its Correlation with Clinical Characteristics of Patients[J].Journal of Modern Laboratory Medicine,2021,36(03):77.[doi:10.3969/j.issn.1671-7414.2021.01.020]
[5]陈丽华,朱婕曼,刘玉凤,等.子宫内膜癌组织中血管紧张素~1-7及线粒体组装受体水平表达与临床病理特征的相关性[J].现代检验医学杂志,2021,36(02):24.[doi:doi:10.3969/j.issn.1671-7414.2021.02.006]
　CHEN Li-hua,ZHU Jie-man,LIU Yu-feng,et al.Correlation between the Expression of Angiotensin (1-7) and Mitochondrial Assembled Receptors and Clinicopathological Characteristics in Endometrial Cancer[J].Journal of Modern Laboratory Medicine,2021,36(03):24.[doi:doi:10.3969/j.issn.1671-7414.2021.02.006]
[6]陈晓宇,曾庆维,陈红林,等.子宫内膜癌组织中miR-3188和mTOR表达量与预后的相关性研究[J].现代检验医学杂志,2021,36(06):17.[doi:10.3969/j.issn.1671-7414.2021.06.004]
　CHEN Xiao-yu,ZENG Qing-wei,CHEN Hong-lin,et al.Study on the Correlation between the Expression Levels of miR-3188 and mTOR in Endometrial Cancer and the Prognosis[J].Journal of Modern Laboratory Medicine,2021,36(03):17.[doi:10.3969/j.issn.1671-7414.2021.06.004]
[7]刘静雅,张海亮,李宝平,等.长链非编码 RNA SNHG1在子宫内膜癌中的表达及调控 PI3K/AKT信号通路的研究[J].现代检验医学杂志,2022,37(01):119.[doi:10.3969/j.issn.1671-7414.2022.01.024]
　LIU Jing-ya,ZHANG Hai-liang,LI Bao-ping,et al.Expression of Long Non-coding RNA SNHG1 in Endometrial Carcinoma and Its Regulation of PI3K/AKT Signaling Pathway[J].Journal of Modern Laboratory Medicine,2022,37(03):119.[doi:10.3969/j.issn.1671-7414.2022.01.024]
[8]彭 浩,张印星,谢 环.长链非编码RNA CDKN2BAS 在子宫内膜癌组织表达及其生物学功能研究[J].现代检验医学杂志,2023,38(03):92.[doi:10.3969/j.issn.1671-7414.2023.03.016]
　PENG Hao,ZHANG Yin-xing,XIE Huan.Expression and Biological Function of Long Non-coding RNA CDKN2BAS in Endometrial Carcinoma[J].Journal of Modern Laboratory Medicine,2023,38(03):92.[doi:10.3969/j.issn.1671-7414.2023.03.016]
[9]梁燕茹,郑 瑜,李 倩.子宫内膜癌患者术前血清apo AI 和Apelin 水平检测对预测淋巴脉管间隙浸润风险的价值研究[J].现代检验医学杂志,2023,38(05):53.[doi:10.3969/j.issn.1671-7414.2023.05.010]
　LIANG Yanru,ZHENG Yu,LI Qian.Value of Preoperative Serum Apo AI and Apelin Levels in Predicting the Risk of Lymph Node Vascular Space Infiltration in Patients with Endometrial Cancer[J].Journal of Modern Laboratory Medicine,2023,38(03):53.[doi:10.3969/j.issn.1671-7414.2023.05.010]
[10]陆 瑞,郭红霞,吴苗苗,等.KIF18B 通过激活Wnt/β catenin 信号通路促进子宫内膜癌细胞增殖和转移的实验研究[J].现代检验医学杂志,2023,38(05):58.[doi:10.3969/j.issn.1671-7414.2023.05.011]
　LU Rui,GUO Hongxia,WU Miaomiao,et al.Experimental Study of KIF18B Promoting Endometrial Cancer Cell Proliferation and Metastasis by Activating Wnt/β-catenin Signaling Pathway[J].Journal of Modern Laboratory Medicine,2023,38(03):58.[doi:10.3969/j.issn.1671-7414.2023.05.011]

备注/Memo

备注/Memo:
基金项目：江苏省连云港市卫生计生科技项目（编号:ZD202005）。
作者简介：张亚军（1979-），男，硕士研究生，副主任技师，主要从事妇科肿瘤与分子病理研究,E-mail:55084970@qq.com。
通讯作者：孟凡菲（1980-），女，硕士研究生，副主任医师，主要从事临床妇产科学方面研究，E-mail:28513572@qq.com。
更新日期/Last Update: 2024-05-15