c-MET和HER2表达改变在膀胱癌中的临床病理意义

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

作者信息

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

机构信息

Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.

Urology Department, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.

出版信息

J Egypt Natl Canc Inst. 2024 Dec 26;36(1):42. doi: 10.1186/s43046-024-00250-2.

DOI:10.1186/s43046-024-00250-2

PMID:39722090

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.

摘要

背景

手术后肿瘤复发或转移是影响膀胱癌（BC）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预后情况。原癌基因MET编码c-MET，一种酪氨酸激酶受体。当c-MET与其配体结合时，它会触发信号转导级联反应中的几个步骤，从而控制细胞存活、增殖和侵袭。c-MET在多种癌症中过表达。HER2基因编码另一种受体酪氨酸激酶（RTK）。HER2过表达与多种恶性肿瘤中增殖改变和侵袭性增加有关。确定参与膀胱癌发生发展的RTK的相互作用伙伴可能在预测侵袭性方面具有独特作用。本研究探讨了c-MET和HER2在人膀胱癌中的表达状况及其在疾病预后中的临床意义。

方法

对40例接受经尿道切除术（TUR）或根治性膀胱切除术且病理确诊为原发性肿瘤且未接受过术前放化疗的膀胱癌患者以及20例作为对照的良性疾病患者进行了定量实时聚合酶链反应。研究了c-MET和HER2的表达水平，并分析了它们与临床病理特征的关系。

结果

与对照组相比，研究组中c-MET和HER2基因表达显著更高，分别为6.1倍和4.5倍。研究组中c-MET和HER2过表达的频率分别为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）、肌肉浸润（P = 0.008）和淋巴结受累（P = 0.017）相关，而HER2过表达与病理分期（P = 0.033）、肌肉浸润（P = 0.003）和淋巴结受累（P = 0.005）相关。基于对数秩检验，在所有研究患者中，同时表达c-MET和HER2的患者无病生存率最差（中位数 = 10个月，95%CI为3.0 - 16.9）。