Hou Guo-Xin, Liu Panpan, Yang Jing, Wen Shijun
Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
PLoS One. 2017 Mar 29;12(3):e0174515. doi: 10.1371/journal.pone.0174515. eCollection 2017.
DNA topoisomerases are essential to modulate DNA topology during various cellular genetic processes. The expression and distinct prognostic value of topoisomerase isoforms in non-small-cell lung cancer (NSCLC) is not well established. In the current study, we have examined the mRNA expression of topoisomerase isoforms by using Oncomine analysis and investigated their prognostic value via the Kaplan-Meier plotter database in NSCLC patients. Our analysis indicated that the expression level of topoisomerases in lung cancer was higher compared with normal tissues. Especially, high expression of two topoisomerase isoforms, TOP2A and TOP3A, was found to be correlated to worse overall survival (OS) in all NSCLC and lung adenocarcinoma (Ade) patients, but not in lung squamous cell carcinoma (SCC) patients. In a contrast, high expression of isoforms TOP1 and TOP2B indicated better OS in all NSCLC and Ade, but not in SCC patients. Meanwhile, high expression of TOP1MT and TOP3B was not correlated with OS in NSCLC patients. Furthermore, we also demonstrated a relationship between topoisomerase isoforms and the clinicopathological features for the NSCLC patients, such as grades, clinical stages, lymph node status, smoking status, gender, chemotherapy and radiotherapy. These results support that TOP2A and TOP3A are associated with worse prognosis in NSCLC patients. In addition, our study also shows that TOP1 and TOP2B contribute to favorable prognosis in NSCLC patients. The exact prognostic significance of TOP1MT and TOP3B need to be further elucidated. Comprehensive evaluation of expression and prognosis of topoisomerase isoforms will be a benefit for the better understanding of heterogeneity and complexity in the molecular biology of NSCLC, paving a way for more accurate prediction of prognosis and discovery of potential drug targets for NSCLC patients.
DNA拓扑异构酶对于在各种细胞遗传过程中调节DNA拓扑结构至关重要。拓扑异构酶亚型在非小细胞肺癌（NSCLC）中的表达及独特的预后价值尚未明确。在本研究中，我们通过Oncomine分析检测了拓扑异构酶亚型的mRNA表达，并通过Kaplan-Meier绘图仪数据库研究了它们在NSCLC患者中的预后价值。我们的分析表明，肺癌中拓扑异构酶的表达水平高于正常组织。特别是，发现两种拓扑异构酶亚型TOP2A和TOP3A的高表达与所有NSCLC和肺腺癌（Ade）患者较差的总生存期（OS）相关，但与肺鳞状细胞癌（SCC）患者无关。相反，TOP1和TOP2B亚型的高表达表明所有NSCLC和Ade患者的OS较好，但SCC患者并非如此。同时，TOP1MT和TOP3B的高表达与NSCLC患者的OS无关。此外，我们还证明了拓扑异构酶亚型与NSCLC患者的临床病理特征之间的关系，如分级、临床分期、淋巴结状态、吸烟状态、性别、化疗和放疗。这些结果支持TOP2A和TOP3A与NSCLC患者较差的预后相关。此外，我们的研究还表明TOP1和TOP2B有助于NSCLC患者的良好预后。TOP1MT和TOP3B的确切预后意义需要进一步阐明。对拓扑异构酶亚型的表达和预后进行综合评估将有助于更好地理解NSCLC分子生物学中的异质性和复杂性，为更准确地预测NSCLC患者的预后和发现潜在的药物靶点铺平道路。
