[1]赵建芳,石 芳,张 昕,等.宫颈癌组织中CSRP2BP mRNA，ESRRB mRNA和蛋白水平表达与上皮间质转化及临床预后相关性研究[J].现代检验医学杂志,2024,39(06):96-101+107.[doi:10.3969/j.issn.1671-7414.2024.06.016]
　ZHAO Jianfang,SHI Fang,ZHANG Xin,et al.Expression of CSRP2BP mRNA，ESRRB mRNA and Protein Levels in Cervical Cancer Tissue and Their Correlation with Epithelial Mesenchymal Transition and Clinical Prognosis[J].Journal of Modern Laboratory Medicine,2024,39(06):96-101+107.[doi:10.3969/j.issn.1671-7414.2024.06.016]
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宫颈癌组织中CSRP2BP mRNA，ESRRB mRNA和蛋白水平表达与上皮间质转化及临床预后相关性研究()
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《现代检验医学杂志》[ISSN:/CN:]

卷:
第39卷
期数:
2024年06期
页码:
96-101+107
栏目:
论著
出版日期:
2024-11-15

文章信息/Info

Title:
Expression of CSRP2BP mRNA，ESRRB mRNA and Protein Levels in Cervical Cancer Tissue and Their Correlation with Epithelial Mesenchymal Transition and Clinical Prognosis
文章编号:
1671-7414（2024）06-096-07
作者:
赵建芳; 石 芳; 张 昕; 贺薇冉
（延安市中医医院/ 北京大学第三医院延安分院病理科，陕西延安 716099）
Author(s):
ZHAO Jianfang; SHI Fang; ZHANG Xin; HE Weiran
（Department of Pathology，Yan’an Traditional Chinese Medicine Hospital/Yan’an Branch of Peking University Third Hospital, Shaanxi Yan’an 716099，China）
关键词:
宫颈癌; 富含半胱氨酸的蛋白质2; 雌激素相关受体β; 上皮间质转化
分类号:
R737.33；R730.43
DOI:
10.3969/j.issn.1671-7414.2024.06.016
文献标志码:
A
摘要:
目的 研究宫颈癌组织中富含半胱氨酸蛋白2 结合蛋白（cysteine rich protein 2 binding protein，CSRP2BP）mRNA，雌激素相关受体β（estrogen related receptors β，ERRB）mRNA 和蛋白表达与上皮间质转化（epithelialmesenchymal transition，EMT）及临床预后的相关性。方法 选择2018 年3 月～ 2020 年3 月延安市中医医院收治的106例宫颈癌患者。采用实时荧光定量PCR（RT-qPCR）检测组织中CSRP2BP mRNA，ESRRB mRNA 及EMT 相关指标［E-钙黏蛋白（E-cadherin，E-cad) ，N- 钙黏蛋白(N-cadherin，N-cad) ，锌指转录因子(Snail family transcriptional repressor，Snail) ］表达。采用免疫组织化学检测组织中CSRP2BP 蛋白，ESRRB 蛋白表达。Pearson 相关分析CSRP2BP mRNA，ESRRB mRNA 与EMT 相关指标的相关性。采用Kaplan-Meier 曲线和COX 回归分析CSRP2BP mRNA，ESRRB mRNA表达对宫颈癌患者预后的影响。结果 癌组织中CSRP2BP mRNA（3.14±0.52 vs 1.22±0.21）和蛋白阳性率（86.79%vs 9.43%），ESRRB mRNA（2.86±0.31 vs 1.06±0.20）和蛋白阳性率（92.45% vs 8.49%），N-cad mRNA（3.22±0.43vs 1.05±0.26），Snail mRNA（2.67±0.36 vs 0.69±0.17）表达高于癌旁组织，E-cad mRNA(0.84±0.17 vs 2.15±0.24)表达低于癌旁组织， 差异具有统计学意义(t/χ2=34.249，127.049；50.234，149.466；44.461，51.204，45.858， 均P<0.001)。宫颈癌中CSRP2BP mRNA，ESRRB mRNA 与N-cad mRNA，Snail mRNA 呈正相关（r=0.663，0.731；0.726，0.715，均P ＜ 0.001），与E-cad mRNA 呈负相关（r=-0.594，-0.669，均P ＜ 0.001）。FIGO 分期Ⅰ B2 ～Ⅱ A，低分化程度及淋巴结转移宫颈癌患者癌组织中CSRP2BP mRNA（4.24±0.57，4.27±0.58，4.24±0.50 ），ESRRB mRNA（4.48±0.36，4.21±0.37，4.69±0.33）高于FIGO 分期Ⅰ A ～Ⅰ B1（2.60±0.44，2.06±0.24），中高分化程度（2.43±0.44，2.01±0.25）及无淋巴结转移（2.53±0.58，2.07±0.26）的患者，差异具有统计学意义（t=16.327，41.135；18.507，36.545；14.501，43.806，均P<0.001）。CSRP2BP mRNA 高表达三年总生存率为66.00%（33/50），低于低表达组的89.29%（50/56）；ESRRB mRNA 高表达组三年总生存率为65.38%（34/52），低于低表达组的90.74%（49/54），差异具有统计学意义（Log-rank χ2=5.401，11.400，P=0.020，0.001）。多因素Cox 回归分析显示，CSRP2BP mRNA 高表达(HR=1.327，95%CI：1.0970 ～ 1.605)、ESRRB mRNA 高表达(HR=1.322，95%CI：1.108 ～ 1.577)、FIGO 分期ⅠB2～ⅡA期(HR=1.423，95%CI：1.154 ～ 1.755)、淋巴结转移(HR=1.363, 95%CI：1.095 ～ 1.698)、低分化程度(HR=1.297,95%CI：1.064 ～ 1.581) 是影响宫颈癌患者预后的危险因素（均P ＜ 0.001）。结论 宫颈癌患者CSRP2BP mRNA，ESRRB mRNA 表达升高，两者与EMT 相关指标及不良临床病理特征有关，是新的预后评估的肿瘤标志物。
Abstract:
Objective To investigate the expression of cysteine rich protein 2 binding protein (CSRP2BP) mRNA and estrogen related receptors β(ESRRB) mRNA and protein in cervical cancer tissues and their correlation with epithelial mesenchymal transition (EMT) and clinical prognosis. Methods A total of 106 cervical cancer patients admitted to Yan’an Traditional Chinese Medicine Hospital from March 2018 to March 2020 were selected. Real time fluorescence quantitative PCR（RT-qPCR） was used to detect CSRP2BP mRNA, ESRRB mRNA and EMT related indicators［E-cadherin(E-cad)，N-cadherin (N-cad)， snail family transcriptional repressor 1(Snail)］.Immunohistochemistry was used to detect the CSRP2BP protein and ESRRB protein expression in tissues.Pearson correlation analysis was used to analyze the correlation between CSRP2BP mRNA, ESRRB mRNA and EMT related indicators. Kaplan-Meier curve and COX regression were used to analyze the effect of CSRP2BP mRNA and ESRRB mRNA expression on the prognosis of cervical cancer patients. Results CSRP2BP mRNA (3.14±0.52 vs 1.22±0.21) expression and protein positive rate (86.79% vs 9.43%), ESRRB mRNA expression (2.86±0.31 vs 1.06±0.20) and protein positive rate (92.45% vs 8.49%), N-cad mRNA (3.22±0.43 vs 1.05±0.26) and Snail mRNA (2.67±0.36 vs 0.69±0.17) expression in cancer tissues were higher than those in adjacent tissues, while E-cad mRNA (0.84±0.17 vs 2.15±0.24)expression was lower than that in adjacent tissues, and the differences were statistically significant (t/χ2=34.249，127.049；50.234， 149.466；44.461，51.204，45.858，all P<0.001).The expression of CSRP2BP mRNA and ESRRB mRNA in cervical cancer was positively correlated with N-cad mRNA and Snail mRNA (r=0.663，0.731；0.726，0.715，all P < 0.001)，and was negatively correlated with E-cad mRNA (r=-0.594，-0.669, all P < 0.001).The expression of CSRP2BP mRNA（4.48±0.36， 4.21±0.37，4.69±0.33） and ESRRB mRNA（4.48±0.36，4.21±0.37，4.69±0.33）in cervical cancer tissues of patients with FIGO stage Ⅰ B2 ～ Ⅱ A, poor differentiation and lymph node metastasis was higher than that of patients with FIGO stage Ⅰ A ～Ⅰ B1（2.60±0.44，2.06±0.24）, medium and high differentiation（2.43±0.44，2.01±0.25） and no lymph node metastasis（2.53±0.58，2.07±0.26）, and the differences were statistically significant (t=16.327，41.135；18.507， 36.545；14.501，43.806， all P<0.001).The 3-year overall survival rate of patients with high expression of CSRP2BP mRNA was 66.00% (33/50), which was lower than 89.29% (50/56) in the low expression group, while the 3-year overall survival rate of the high expression group of ESRRB mRNA was 65.38% (34/52), which was lower than 90.74% (49/54) of the low expression group，and the differences were statistically significant (Log rank χ2=5.401，11.400，P=0.020，0.001）.Multivariate Cox regression analysis showed that, CSRP2BP mRNA high expression (HR=1.327,95%CI:1.097 ～ 1.605), ESRRB mRNA high expression (HR=1.322, 95%CI:1.108 ～ 1.577), FIGO stage Ⅰ B2 ～ Ⅱ A (HR=1.423, 95%CI:1.154 ～ 1.755), lymph node metastasis (HR=1.363, 95%CI:1.095 ～ 1.698) and poor differentiation (HR=1.297, 95%CI:1.064 ～ 1.581) were risk factors affecting the prognosis of cervical cancer patients (all P < 0.001).Conclusion The increased expression of CSRP2BP mRNA and ESRRB mRNA in cervical cancer are related to EMT related indicators and adverse clinical and pathological features, and are new tumor markers for prognostic evaluation.

参考文献/References:

[1] BUSKWOFIE A, DAVID-WEST G, CLARE C A. A review of cervical cancer: incidence and disparities[J]. Journal of the National Medical Association, 2020,112(2): 229-232.
[2] 高红敏, 杨红英, 刘鑫. 血清中microRNA-106b 对宫颈癌患者的早期诊断及预后预测价值[J]. 现代检验医学杂志, 2020, 35(6): 85-86, 182. GAO Hongmin, YANG Hongying, LIU Xin. Value analysis of serum microRNA-106b in early diagnosis of cervical cancer[J]. Journal of Modern Laboratory Medicine, 2020, 35(6): 85-86, 182.
[3] WANG Ziwei, LIU Yan, ZHANG Jun, et al. An immune-related long noncoding RNA signature as a prognostic biomarker for human endometrial cancer[J]. Journal of Oncology, 2021, 2021: 9972454.
[4] BERSELLI A, BENFENATI F, MARAGLIANO L, et al. Multiscale modelling of claudin-based assemblies: a magnifying glass for novel structures of biological interfaces[J]. Computational and Structural Biotechnology Journal, 2022, 20: 5984-6010.
[5] HAO Shiyu, YANG Chunyan, SONG Peng, et al. CLDN4 promotes growth of acute myeloid leukemia cells via regulating AKT and ERK1/2 signaling[J]. Biochemical and Biophysical Research Communications, 2022, 619: 137-143.
[6] HU Pan, LEI Li, WANG Ying, et al. CLDN4 as a novel diagnostic and prognostic biomarker and its association with immune infiltrates in ovarian cancer[J]. Mediators of Inflammation, 2023, 2023: 1075265.
[7] XU Yichi, PAN Shuya, CHEN Hong, et al. MEX3A suppresses proliferation and EMT via inhibiting Akt signaling pathway in cervical cancer[J]. American Journal of Cancer Research, 2021, 11(4): 1446-1462.
[8] LI Jina, LIU Gaoming, LUO Jiayou, et al. Cervical cancer prognosis and related risk factors for patients with cervical cancer: a long-term retrospective cohort study[J]. Scientific Reports, 2022, 12(1): 13994.
[9] FANG Chenyan, ZHANG Ping, YU Aijun, et al. Different prognosis of stage IIIB cervical cancer patients with lower third of vaginal invasion and those without[J]. Gynecologic Oncology, 2021, 162(1): 50-55.
[10] LIAO Yuandong, HUANG Jiaming, LIU Pan, et al. Downregulation of LNMAS orchestrates partial EMT and immune escape from macrophage phagocytosis to promote lymph node metastasis of cervical cancer[J]. Oncogene, 2022, 41(13): 1931-1943.
[11] LUO Aoran, LAN Xiaoxiao, QIU Qiongzi, et al. LncRNA SFTA1P promotes cervical cancer progression by interaction with PTBP1 to facilitate TPM4 mRNA degradation[J]. Cell Death & Disease, 2022, 13(11): 936.
[12] HAN Sai, LIU Xiaoli, JU Shuang, et al. New mechanisms and biomarkers of lymph node metastasis in cervical cancer: reflections from plasma proteomics[J]. Clinical Proteomics, 2023, 20(1): 35.
[13] BERSELLI A, ALBERINI G, BENFENATI F, et al. Computational study of ion permeation through claudin-4 paracellular channels[J]. Annals of the New York Academy of Sciences, 2022, 1516(1): 162-174.
[14] JIE Youkun, YE Lu, CHEN He, et al. ELFN1-AS1 accelerates cell proliferation, invasion and migration via regulating miR-497-3p/CLDN4 axis in ovarian cancer[J]. Bioengineered, 2020, 11(1): 872-882.
[15] WANG Hao, XU Hongfa, MA Feng, et al. Zinc finger protein 703 induces EMT and sorafenib resistance in hepatocellular carcinoma by transactivating CLDN4 expression[J]. Cell Death & Disease, 2020, 11(4): 225.
[16] LIN Heng, KRYCZEK I, LI Shasha, et al. Stanniocalcin 1 is a phagocytosis checkpoint driving tumor immune resistance[J]. Cancer Cell, 2021, 39(4): 480-493. e6.
[17] KROEMER G, ZITVOGEL L. Subversion of calreticulin exposure as a strategy of immune escape[J]. Cancer Cell, 2021, 39(4): 449-451.
[18] ZHU Jiaqi, JIANG Qi. Twist1-mediated transcriptional activation of Claudin-4 promotes cervical cancer cell migration and invasion[J]. Oncology Letters, 2023, 26(2): 335.
[19] FUJIWARA-TANI R, MORI S, OGATA R, et al. Claudin-4: a new molecular target for epithelial cancer therapy[J]. International Journal of Molecular Sciences, 2023, 24(6): 5494.
[20] LUO Jie, WANG Huaiming, CHEN Huanjie, et al. CLDN4 silencing promotes proliferation and reduces chemotherapy sensitivity of gastric cancer cells through activation of the PI3K/Akt signalling pathway[J]. Experimental Physiology, 2020, 105(6): 979-988.

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备注/Memo

备注/Memo:
基金项目：陕西省卫生健康科研项目（2022D0024）。
作者简介：赵建芳（1979-），女，本科，副主任医师，研究方向：妇科肿瘤，E-mail：zhaojf2017@163.com。
通讯作者：石芳（1981-），女，本科，副主任医师，研究方向：妇科肿瘤，E-mail：541120368@qq.com。
更新日期/Last Update: 2024-11-15