Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan,
Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan,
Oncology. 2022;100(9):485-497. doi: 10.1159/000525743. Epub 2022 Jul 11.
Dysregulation of metal ion homeostasis is associated with urothelial carcinogenesis. From a published urinary bladder urothelial carcinoma (UBUC) transcriptome, we identified metallothionein 2A (MT2A) as the most significantly upregulated gene implicated in cancer progression among metal ion binding-related genes. Therefore, we analyzed the association between MT2A expression and clinical significance in our well-characterized cohort of patients with upper tract urothelial carcinoma (UTUC) and UBUC. We retrospectively reviewed the clinicopathological characteristics of 295 and 340 patients with UBUC and UTUC, respectively. MT2A expression was assessed using real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry. We further correlated MT2A expression with clinicopathological factors, disease-specific survival (DSS) and metastasis-free survival (MFS) using the Pearson's χ test, Kaplan-Meier analysis, and multivariate Cox proportional hazards model. High MT2A expression was significantly associated with aggressive pathological features including high tumor stage, lymph node metastasis, high tumor grade, vascular invasion, and perineural invasion. In the Kaplan-Meier analysis, high MT2A expression was significantly correlated with poor DSS ( < 0.0001) and MFS ( < 0.0001); in the multivariate analysis, it was an independent predictor of CSS ( < 0.001) and MFS ( = 0.001). Gene coexpression analysis demonstrated that MT2A overexpression promotes UC progression through complement activation. High MT2A expression correlated with aggressive UC features and was an independent predictor of cancer metastasis and patient survival, suggesting its role in risk stratification and decision-making in patients with UTUC and UBUC.
金属离子动态平衡失调与尿路上皮癌的发生有关。从已发表的尿路上皮膀胱癌（UBUC）转录组中，我们发现金属硫蛋白 2A（MT2A）是与金属离子结合相关基因中与癌症进展最相关的上调最明显的基因。因此，我们分析了 MT2A 表达与我们具有良好特征的上尿路尿路上皮癌（UTUC）和 UBUC 患者的临床意义之间的关系。我们回顾性分析了 295 例 UBUC 和 340 例 UTUC 患者的临床病理特征。使用实时逆转录-聚合酶链反应和免疫组织化学评估 MT2A 表达。我们使用 Pearson χ检验、Kaplan-Meier 分析和多变量 Cox 比例风险模型进一步将 MT2A 表达与临床病理因素、疾病特异性生存（DSS）和无转移生存（MFS）相关联。高 MT2A 表达与侵袭性病理特征显著相关，包括高肿瘤分期、淋巴结转移、高肿瘤分级、血管浸润和神经周围浸润。在 Kaplan-Meier 分析中，高 MT2A 表达与较差的 DSS（<0.0001）和 MFS（<0.0001）显著相关；在多变量分析中，它是 CSS（<0.001）和 MFS（=0.001）的独立预测因子。基因共表达分析表明，MT2A 过表达通过补体激活促进 UC 进展。高 MT2A 表达与侵袭性 UC 特征相关，是癌症转移和患者生存的独立预测因子，表明其在 UTUC 和 UBUC 患者的风险分层和决策中的作用。
