CTNNB1、Grb2在卵巢癌组织中的表达水平及其病理预后意义

doi:10.3870/j.issn.1672-8009.2026.02.014

摘要/Abstract

摘要： 目的探讨β-连环蛋白1(catenin beta 1,CTNNB1)、生长因子受体结合蛋白2(growth factor receptor-bound protein 2,Grb2)在卵巢癌组织中的表达水平及其病理预后意义。方法选取2019年1月至2022年1月于沧州市中心医院接受治疗的126例卵巢癌患者,将癌组织标本纳入卵巢癌组,将距离病灶边缘1 cm及以上的癌旁组织标本纳入癌旁组。免疫组织化学法检测组织中CTNNB1、Grb2表达情况。采用χ²检验分析CTNNB1、Grb2与患者病理特征的关系,使用多因素Cox回归分析预后影响因素。结果卵巢癌组中CTNNB1、Grb2阳性率高于癌旁组(61.90 % vs 30.95 %,65.08 % vs 33.33 %;P<0.05)。低分化、FIGO分期Ⅲ~Ⅳ期、有淋巴结转移、有腹腔积液患者CTNNB1、Grb2阳性率分别高于中/高分化程度、FIGO分期Ⅰ~Ⅱ期、无淋巴结转移、无腹腔积液患者(P<0.05)。CTNNB1、Grb2阳性患者总生存率分别低于CTNNB1、Grb2阴性患者(53.85 % vs 81.25 %,54.88 % vs 81.81 %;P<0.05)。多因素分析显示,低分化(HR=3.065,95 %CI:1.348~6.967)、淋巴结转移(HR=2.765,95 %CI:1.401~5.458)、CTNNB1阳性(HR=3.080,95 %CI:1.594~5.951)、Grb2阳性(HR=3.062,95 %CI:1.536~6.104)是卵巢癌患者预后的独立危险因素(P<0.05)。结论 CTNNB1、Grb2在卵巢癌组织中主要呈阳性表达,与分期、分化程度、淋巴结转移显著相关,二者可作为辅助评估患者预后的生物标记物。

关键词: β-连环蛋白1, 生长因子受体结合蛋白2, 卵巢癌, 预后

Abstract: Objective To investigate the expression levels of catenin beta 1(CTNNB1)and growth factor receptor-bound protein 2(Grb2)in ovarian cancer tissues and their prognostic significance.Methods A total of 126 patients with ovarian cancer who were treated in Cangzhou Central Hospital from January 2019 to January 2022 were selected.Samples of the cancer tissue were included in the ovarian cancer group(n= 126),and samples of adjacent tissues at least 1 cm away from the lesion margin were included in the adjacent tissue group(n= 126).The expression of CTNNB1 and Grb2 in the tissues was detected by immunohistochemistry.The relationship between the CTNNB1,Grb2 and the clinicopathological characteristics of ovarian cancer patients were analyzed by χ² test.The influencing factors of prognosis in ovarian cancer patients were analyzed by multivariate Cox regression.Results The positive rate of CTNNB1 and Grb2 in the ovarian cancer group was higher than that in the adjacent tissue group(61.90 % vs 30.95 %,65.08 % vs 33.33 %;P<0.05).The positive expression rate of CTNNB1 and Grb2 in patients with low differentiation,FIGO stage Ⅲ-Ⅳ,lymph node metastasis,and ascites was higher than that in those with moderate/high differentiation,FIGO stage Ⅰ-Ⅱ,no lymph node metastasis,and no ascites(P<0.05).The 3-year overall survival rate of patients with positive CTNNB1 and Grb2 was lower than that of those with negative CTNNB1 and Grb2(53.85 %vs 81.25 %,54.88 %vs 81.81 %,P<0.05).Multivariate analysis showed that low differentiation(HR=3.065,95 %CI:1.348-6.967),lymph node metastasis(HR=2.765,95 %CI:1.401-5.458),positive CTNNB1(HR=3.080,95 %CI:1.594-5.951),and positive Grb2(HR=3.062,95 %CI:1.536-6.104)were independent risk factors affecting the prognosis of ovarian cancer patients(P<0.05).Conclusion CTNNB1 and Grb2 are highly expressed in ovarian cancer tissues and are significantly associated with FIGO stage,differentiation degree,lymph node metastasis,and ascites.Both of them can be used as biomarkers for auxiliary assessment of patient prognosis.

Key words: catenin beta 1, growth factor receptor-bound protein 2, ovarian cancer, prognosis

中图分类号:

R737.31

高文英, 刘世凯, 姚海荣. CTNNB1、Grb2在卵巢癌组织中的表达水平及其病理预后意义[J]. 医学分子生物学杂志, 2026, 23(2): 212-217.

GAO Wenying, LIU Shikai, YAO Hairong. Expression Levels of CTNNB1 and Grb2 in Ovarian Cancer Tissues and Their Prognostic Significance[J]. Journal of Medical Molecular Biology, 2026, 23(2): 212-217.

参考文献

[1] 沈梦醒,姚海荣,王振影.miR-377-3p对上皮性卵巢癌SKOV3细胞增殖和凋亡的影响[J].医学分子生物学杂志,2025,22(5):482-487.
SHEN M X,YAO H L,WANG Z Y.Effect of mir-377-3p on proliferation and apoptosis of epithelial ovarian cancer SKOV3 cells[J].J Med Mol Biol,2025,22(5):482-487.
[2] 叶晶,赵金荣,李萍,等.奥拉帕尼对卵巢癌ES2细胞生存、上皮细胞间质转换及肿瘤干细胞样特性的调节作用[J].医学分子生物学杂志,2025,22(3):217-222.
YE J,ZHAO J R,LI P,et al Regulatory effects ofolaparib on survival,epithelial mesenchymal transition and tumor stem cell like characteristics of ovarian cancer ES2 cells[J].J Med Mol Biol,2025,22(3):217-222.
[3] 华美萍,吴晓燕,王翠霞.经阴道超声联合血清CA19-9、CA125水平对卵巢肿瘤良恶性的诊断效能[J].转化医学杂志,2024,13(5):727-732.
HUA M P,WU X Y,WANG C X.Diagnostic efficacy of transvaginal ultrasound combined with Serum CA19-9 and CA125 levels for benign and malignant ovarian tumors[J].J Transl Med,2024,13(5):727-732.
[4] LEDINEK Ž,SOBOČAN M,KNEZ J.The role of CTNNB1 in endometrial cancer[J].Dis Markers,2022,2022:1442441.
[5] YE Z,XU S,SHI Y,et al.GRB2 stabilizes RAD51 at reversed replication forks suppressing genomic instability and innate immunity against cancer[J].Nat Commun,2024,15(1):2132.
[6] 周琦,吴小华,刘继红,等.卵巢恶性肿瘤诊断与治疗指南(第四版)[J].中国实用妇科与产科杂志,2018,34(7):739-749.
ZHOU Q,WU X H,LIU J H,et al.Guidelines for the diagnosis and treatment of ovarian malignancies(FourthEdition)[J].Chin J Pract Gynecol Obstet,2018,34(7):739-749.
[7] 杜燕子,刘成云,马娇荣.卵巢癌组织中CD177、FUBP1、HOXA1的表达情况及其临床意义[J].中国性科学,2025,34(3):85-90.
DU Y Z,LIU C Y,MA J R.Expression and clinical significance of CD177,fubp1,Hoxa1 in ovarian cancer[J].Chin J Sex Sci,2025,34(3):85-90.
[8] 郭莉,马瑞风,董玉.CXCL10、LPA蛋白在卵巢癌组织中的表达及与预后的关系[J].临床误诊误治,2023,36(8):80-83,93.
GUO L,MA R F,DONG Y.Expression of CXCL10 and LPA proteins in ovarian cancer and their relationship with prognosis[J].Clin Misdiagn Mistr,2023,36(8):80-83,93.
[9] KONSTANTINOPOULOS P A,MATULONIS U A.Clinical and translational advances in ovarian cancer therapy[J].Nat Cancer,2023,4(9):1239-1257.
[10] ZHANG R,SIU M K Y,NGAN H Y S,et al.Molecular biomarkers for the early detection of ovarian cancer[J].Int J Mol Sci,2022,23(19):12041.
[11] LIANG B,ZHOU Y,QIAN M,et al.TBX3 functions as a tumor suppressor downstream of activated CTNNB1 mutants during hepatocarcinogenesis[J].J Hepatol,2021,75(1):120-131.
[12] HE S,TANG S.WNT/β-catenin signaling in the development of liver cancers[J].Biomed Pharmacother,2020,132:110851.
[13] YU F,YU C,LI F,et al.Wnt/β-catenin signaling in cancers and targeted therapies[J].Signal Transduct Target Ther,2021,6(1):307.
[14] HAN T,GAO M,WANG X,et al.LINC00665 activates Wnt/β-catenin signaling pathway to facilitate tumor progression of colorectal cancerviaupregulating CTNNB1[J].Exp Mol Pathol,2021,120:104639.
[15] MONTERO-VERGARA J,PLACHETTA K,KINCH L,et al.GRB2 is a BECN1 interacting protein that regulates autophagy[J].Cell Death Dis,2024,15(1):14.
[16] WANG D,LIU G,MENG Y,et al.The configuration of GRB2 in protein interaction and signal transduction[J].Biomolecules,2024,14(3):259.
[17] SAYEESH P M,IGUCHI M,INOMATA K,et al.Structure and dynamics of drk-SH2 domain and its site-specific interaction with sev receptor tyrosine kinase[J].Int J Mol Sci,2024,25(12):6386.
[18] ZHANG Y,DING L,NI Q,et al.Transcription factor PAX4 facilitates gastric cancer progression through interacting with miR-27b-3p/Grb2 axis[J].Aging,2021,13(12):16786-16803.
[19] 毛星刚.胶质母细胞瘤中缺氧巨噬细胞的鉴定及其使血管正常化的治疗潜力[J].中华神经外科疾病研究杂志,2024,18(5):14.
MAO X G.Identification of hypoxic macrophages in glioblastoma and their therapeutic potential to normalize blood vessels[J].Chin J Neurosurg Dis Res,2024,18(5):14.
[20] 吕瑞,姬昂,薛小燕,等.胶质母细胞瘤中免疫和小胶质/巨噬细胞的特异性高表达基因具有间充质亚型的特性[J].中华神经外科疾病研究杂志,2024,18(1):38-45.
LU R,JI A,XUE X Y,et al.The specific highly expressed genes of immunity and microglia / macrophages in glioblastoma have the characteristics of mesenchymal subtype[J].Chin J Neurosurg Dis Res,2024,18(1):38-45.