|Table of Contents|

Expression of p-ERK5 and WT-1 in high-grade serous ovarian cancer and their relationships with clinicopathological features

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2024 14
Page:
2596-2600
Research Field:
Publishing date:

Info

Title:
Expression of p-ERK5 and WT-1 in high-grade serous ovarian cancer and their relationships with clinicopathological features
Author(s):
WANG Yanmin1; 2; GUO Yanjuan1; LIU Conghui1; CHEN Yan1
1.North China University of Technology Affiliated Hospital,Hebei Tangshan 063000,China;2.Luanzhou People's Hospital,Hebei Luanzhou 063700,China.
Keywords:
high-grade serous ovarian cancer; p-ERK5; WT-1; immunohistochemistry; clinicopathological features
PACS:
R737.31
DOI:
10.3969/j.issn.1672-4992.2024.14.018
Abstract:
Objective:To detect the expression levels of p-ERK5 and WT-1 proteins in ovarian benign and malignant tumor tissues,and the relationship between the expression levels of p-ERK5 and WT-1 proteins in ovarian cancer was analyzed.The relationships between p-ERK5,WT-1 protein and clinicopathological features of high-grade serous ovarian cancer were analyzed to provide new ideas for the diagnosis and treatment of ovarian cancer.Methods:Patients with ovarian tumor were selected from the Department of Gynecology,Affiliated Hospital of North China University of Technology from January 2008 to December 2019.The subjects were selected according to the first pathological diagnosis.This study is divided into two parts.In the first part,54 HSOC patients were selected as case group,50 ovarian serous cystadenoma patients as control group.The clinical and pathological data of ovarian tumor were collected.The expression levels of p-ERK5 and WT-1 protein in ovarian tumors were detected by immunohistochemistry.In the second part,54 HSOC patients were selected.According to the expression of p-ERK5 and WT-1 protein,they were divided into low expression group and high expression group.The expression of p-ERK5 and WT-1 protein in benign and malignant ovarian tumors were compared by t test and χ2 test.χ2 test,Fisher's exact probability method,non-parametric Mann-whitney U test and multivariate Logistic regression were used to analyze the relationship between their expression levels and clinicopathological characteristics of high-grade serous ovarian cancer.Results:The high expression of p-ERK5 and WT-1 protein in case group were significantly higher than those in control group (P＜0.05).The expression of p-ERK5 and WT-1 was associated with clinical stage,lymph node metastasis and recurrence within 3 years in univariate analysis.The high expression rates of p-ERK5 and WT-1 were significantly increased in patients with high clinical stage,lymph node metastasis and recurrence within 3 years.The high expression rate of p-ERK5 was significantly increased in patients with combined ascites.The level of CA125 in patients with high expression of p-ERK5 and WT-1 was significantly higher than that in patients with low expression of p-ERK5 and WT-1(P＜0.05).The high expression of p-ERK5 and WT-1 were risk factors for lymphatic metastasis and recurrence within 3 years after treatment in multivariate Logistic regression analysis.Conclusion:The high expression of p-ERK5 and WT-1 proteins is related to the clinicopathological features of ovarian cancer.The patients are more likely to have lymphatic metastasis and recurrence within 3 years after initial treatment.

References:

［1］ SIEGEL RL,GIAQUINTO AN,JEMAL A.Cancer statistics,2024［J］.CA Cancer J Clin,2024,74(1):12-49.
［2］ WEBB PM,JORDAN SJ.Global epidemiology of epithelial ovarian cancer［J］.Nat Rev Clin Oncol,2024,21(5):389-400.
［3］ XU Q,ZHANG J,TELFER BA,et al.The extracellular-regulated protein kinase 5 (ERK5) enhances metastatic burden in triple-negative breast cancer through focal adhesion protein kinase (FAK)-mediated regulation of cell adhesion［J］.Oncogene,2021,40(23):3929-3941.
［4］ DENG J,LIU L,LI L,et al.Hesperidin delays cell cycle progression into the G0/G1 phase via suspension of MAPK signaling pathway in intrahepatic cholangiocarcinoma［J］.J Biochem Mol Toxicol,2022,36(4):e22981.
［5］ SNCHEZ-FDEZ A,MATILLA-ALMAZN S,MONTERO JC,et al.The WNK1-ERK5 route plays a pathophysiological role in ovarian cancer and limits therapeutic efficacy of trametinib［J］.Clin Transl Med,2023,13(4):e1217.
［6］ 翟阳，廖子君，王玉珍，等.WT1和VEGF在结肠癌组织中的表达及其与甲磺酸阿帕替尼疗效的相关性［J］.现代肿瘤医学,2019,27(22):4040-4043. ZHAI Y,LIAO ZJ,WANG YZ,et al.The expression of WT1 and VEGF in colon cancer and their correlation with Apatinib effect of methanesulfonate［J］.Modern Oncology,2019,27(22):4040-4043.
［7］ HAN Y,SONG C,ZHANG T,et al.Wilms' tumor 1 (WT1) promotes ovarian cancer progression by regulating E-cadherin and ERK1/2 signaling［J］.Cell Cycle,2020,19(20):2662-2675.
［8］ DALMARTELLO M,LA VECCHIA C,BERTUCCIO P,et al.European cancer mortality predictions for the year 2022 with focus on ovarian cancer［J］.Ann Oncol,2022,33(3):330-339.
［9］ MOUFARRIJ S,DANDAPANI M,ARTHOFER E,et al.Epigenetic therapy for ovarian cancer:promiseand progress［J］.Clin Epigenetics,2019,11(1):7
［10］ LEE S,YANG W,KIM DK,et al.Inhibition of MEK-ERK pathway enhances oncolytic vaccinia virus replication in doxorubicin-resistant ovarian cancer［J］.Mol Ther Oncolytics,2022,25:211-224.
［11］ TUBITA A,LOMBARDI Z,TUSA I,et al.Beyond kinase activity:ERK5 nucleo-cytoplasmic shuttling as a novel target for anticancer therapy［J］.Int J Mol Sci,2020,21(3):938.
［12］ ZHANG M,SHI R,GUO Z,et al.Cancer-associated fibroblasts promote cell growth by activating ERK5/PD-L1 signaling axis in colorectal cancer［J］.Pathol Res Pract,2020,216(4):152884.
［13］ WANG G,ZHAO Y,LIU Y,et al.Discovery of a novel dual-target inhibitor of ERK1 and ERK5 that induces regulated cell death to overcome compensatory mechanism in specific tumor types［J］.J Med Chem,2020,63(8):3976-3995.
［14］ BHATT AB,WRIGHT TD,BARNES V,et al.Diverse and converging roles of ERK1/2 and ERK5 pathways on mesenchymal to epithelial transition in breast cancer［J］.Transl Oncol,2021,14(6):101046.
［15］ GENTILINI A,LORI G,CALIGIURI A,et al.Extracellular signal-regulated kinase 5 regulates the malignant phenotype of cholangiocarcinoma cells［J］.Hepatology,2021,74(4):2007-2020.
［16］ ZHANG J,PEARSON AJ,SABHERWAL N,et al.Inhibiting ERK5 overcomes breast cancer resistance to anti-HER2 therapy by targeting the G1/S cell cycle transition［J］.Cancer Res Commun,2022,2(3):131-145.
［17］ WANG L,JI X,MAO C,et al.BAY-885,a mitogen-activated protein kinase kinase 5 inhibitor,induces apoptosis by regulating the endoplasmic reticulum stress/Mcl-1/Bim pathway in breast cancer cells［J］.Bioengineered,2022,13(5):12888-12898.
［18］ HEIN KZ,YAO S,FU S.Wilms' tumor 1 (WT-1):The vaccine for cancer［J］.J Immunother Precis Oncol,2020,3(4):165-171.
［19］ TAUBE ET,DENKERT C,SEHOULI J,et al.Wilms tumor protein 1 (WT1)-not only a diagnostic but also a prognostic marker in high-grade serous ovarian carcinoma［J］.Gynecol Oncol,2016,140(3):494-502.
［20］ LILI LN,MATYUNINA LV,WALKER LD,et al.Molecular profiling supports the role of epithelial-to-mesenchymal transition (EMT) in ovarian cancer metastasis［J］.J Ovarian Res,2013,6(1):49.
［21］ CARTER JH,DEDDENS JA,MUELLER G,et al.Transcription factors WT-1 and p53 combined:a prognostic biomarker in ovarian cancer［J］.Br J Cancer,2018,119(4):462-470.
［22］ ABD EL-HAFEZ A,ISMAIL HANY HSED.WT-1 clone 6F-H2 cytoplasmic expression differentiates astrocytic tumors from astrogliosis and associates with tumor grade,histopathology,IDH1 status,apoptotic and proliferative indices:A tissue microarray study［J］.Asian Pac J Cancer Prev,2020,21(8):2403-2413.
［23］ ITO M,OJI Y,ADACHI M,et al.Serum WT-1-271 IgM antibody as a novel diagnostic marker for gastric cancer［J］.Mol Clin Oncol,2022,16(3):74

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河北省医学科学研究课题计划项目（编号：20231260）
Last Update: 1900-01-01