Clinicopathological significance of c-MET and HER2 altered expression in bladder cancer.

IF 2.1 Q3 ONCOLOGY

Journal of the Egyptian National Cancer Institute Pub Date : 2024-12-26 DOI:10.1186/s43046-024-00250-2

Engy Mohammed Naguib, E F Ismail, D I Badran, M H Sherief, T B El-Abaseri

{"title":"Clinicopathological significance of c-MET and HER2 altered expression in bladder cancer.","authors":"Engy Mohammed Naguib, E F Ismail, D I Badran, M H Sherief, T B El-Abaseri","doi":"10.1186/s43046-024-00250-2","DOIUrl":null,"url":null,"abstract":"Background: Tumor recurrence or metastasis after surgery is a significant factor influencing bladder cancer (BC) prognosis. Novel molecular biomarkers are necessary to determine each patient's specific outcome because current biomarkers have limited power for predicting prognosis. The proto-oncogene MET encodes c-MET, a tyrosine kinase receptor. When c-MET attaches to its ligand, it triggers several steps in the signal transduction cascade that control cell survival, proliferation, and invasion. c-MET is overexpressed in several carcinomas. The HER2 gene encodes another receptor tyrosine kinase (RTK). HER2 overexpression is linked to altered proliferation and increased aggressiveness in several malignancies. Identifying crosstalk partners of RTKs implicated in bladder cancer development may have a unique role in predicting aggressiveness. This study explored the expression status of c-MET and HER2 in human BC and their clinical significance in disease outcomes.Methods: A quantitative real-time polymerase chain reaction was done on 40 BC patients who had undergone transurethral resection (TUR) or radical cystectomy and had a pathologically verified diagnosis of primary tumor without prior chemoradiotherapy as well as 20 patients with benign diseases who served as controls. The c-MET and HER2 expression levels were investigated, and their relationship with clinicopathological features was analyzed.Results: c-MET and HER2 gene expression were significantly higher, 6.1- and 4.5-fold, in the study group compared to the controls. The frequency of c-MET and HER2 overexpression in the study group was 80% (32/40) and 90% (36/40), respectively. c-MET overexpression was associated with pathological stage(P = 0.002), tumor grade (P = 0.019), muscle invasion (P = 0.008), and node involvement (P = 0.017), while HER2 overexpression was associated with pathological stage(P = 0.033), invasion to muscles (P = 0.003), and node involvement (P = 0.005). Based on the Log-rank test, patients expressing both c-MET and HER2 had the poorest disease-free survival rates among all studied patients (median = 10 m, 3.0-16.9 95%CI).Conclusion: There is a possible correlation between c-MET and HER2 gene overexpression and poor clinical outcomes in patients with BC.","PeriodicalId":17301,"journal":{"name":"Journal of the Egyptian National Cancer Institute","volume":"36 1","pages":"42"},"PeriodicalIF":2.1000,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of the Egyptian National Cancer Institute","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1186/s43046-024-00250-2","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Tumor recurrence or metastasis after surgery is a significant factor influencing bladder cancer (BC) prognosis. Novel molecular biomarkers are necessary to determine each patient's specific outcome because current biomarkers have limited power for predicting prognosis. The proto-oncogene MET encodes c-MET, a tyrosine kinase receptor. When c-MET attaches to its ligand, it triggers several steps in the signal transduction cascade that control cell survival, proliferation, and invasion. c-MET is overexpressed in several carcinomas. The HER2 gene encodes another receptor tyrosine kinase (RTK). HER2 overexpression is linked to altered proliferation and increased aggressiveness in several malignancies. Identifying crosstalk partners of RTKs implicated in bladder cancer development may have a unique role in predicting aggressiveness. This study explored the expression status of c-MET and HER2 in human BC and their clinical significance in disease outcomes.

Methods: A quantitative real-time polymerase chain reaction was done on 40 BC patients who had undergone transurethral resection (TUR) or radical cystectomy and had a pathologically verified diagnosis of primary tumor without prior chemoradiotherapy as well as 20 patients with benign diseases who served as controls. The c-MET and HER2 expression levels were investigated, and their relationship with clinicopathological features was analyzed.

Results: c-MET and HER2 gene expression were significantly higher, 6.1- and 4.5-fold, in the study group compared to the controls. The frequency of c-MET and HER2 overexpression in the study group was 80% (32/40) and 90% (36/40), respectively. c-MET overexpression was associated with pathological stage(P = 0.002), tumor grade (P = 0.019), muscle invasion (P = 0.008), and node involvement (P = 0.017), while HER2 overexpression was associated with pathological stage(P = 0.033), invasion to muscles (P = 0.003), and node involvement (P = 0.005). Based on the Log-rank test, patients expressing both c-MET and HER2 had the poorest disease-free survival rates among all studied patients (median = 10 m, 3.0-16.9 95%CI).

Conclusion: There is a possible correlation between c-MET and HER2 gene overexpression and poor clinical outcomes in patients with BC.

查看原文本刊更多论文

c-MET和HER2在膀胱癌中表达改变的临床病理意义。

背景：术后肿瘤复发或转移是影响膀胱癌预后的重要因素。由于目前的生物标志物预测预后的能力有限，因此需要新的分子生物标志物来确定每个患者的具体结果。原癌基因MET编码c-MET，一种酪氨酸激酶受体。当c-MET附着在其配体上时，它会触发信号转导级联中的几个步骤，控制细胞的存活、增殖和侵袭。c-MET在几种癌中过表达。HER2基因编码另一种受体酪氨酸激酶（RTK）。HER2过表达与几种恶性肿瘤的增殖改变和侵袭性增加有关。识别与膀胱癌发展相关的rtk的相声伙伴可能在预测侵袭性方面具有独特的作用。本研究探讨c-MET和HER2在人BC中的表达状况及其在疾病转归中的临床意义。方法：对40例经尿道膀胱切除术（TUR）或根治性膀胱切除术，病理证实原发肿瘤且未进行放化疗的BC患者，以及20例良性疾病患者作为对照，进行定量实时聚合酶链反应。观察c-MET和HER2的表达水平，并分析其与临床病理特征的关系。结果：研究组c-MET和HER2基因的表达明显高于对照组，分别为6.1倍和4.5倍。研究组c-MET和HER2过表达频率分别为80%（32/40）和90%（36/40）。c-MET过表达与病理分期（P = 0.002）、肿瘤分级（P = 0.019）、肌肉侵袭（P = 0.008）、淋巴结受累（P = 0.017）相关，而HER2过表达与病理分期（P = 0.033）、肌肉侵袭（P = 0.003）、淋巴结受累（P = 0.005）相关。根据Log-rank检验，同时表达c-MET和HER2的患者在所有研究患者中无病生存率最低（中位数= 10 m, 3.0-16.9 95%CI）。结论：c-MET和HER2基因过表达与BC患者临床预后不良可能存在相关性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of the Egyptian National Cancer Institute ONCOLOGY-

CiteScore

3.50

自引率

0.00%

发文量

审稿时长

11 weeks

期刊介绍： As the official publication of the National Cancer Institute, Cairo University, the Journal of the Egyptian National Cancer Institute (JENCI) is an open access peer-reviewed journal that publishes on the latest innovations in oncology and thereby, providing academics and clinicians a leading research platform. JENCI welcomes submissions pertaining to all fields of basic, applied and clinical cancer research. Main topics of interest include: local and systemic anticancer therapy (with specific interest on applied cancer research from developing countries); experimental oncology; early cancer detection; randomized trials (including negatives ones); and key emerging fields of personalized medicine, such as molecular pathology, bioinformatics, and biotechnologies.