Abstract
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.
Highlights
Lung cancer is the most common cause of cancer-related deaths worldwide
Using the Kaplan-Meier plotter, we demonstrate that high expression of TOP2A and TOP3A is correlated to worse overall survival (OS) in all non-small-cell lung cancer (NSCLC) patients as well as in Ade, but not in squamous cell carcinoma (SCC) patients
High expression of TOP1 and TOP2B is found to be associated with better OS in all NSCLC patients as well as in Ade, but not in SCC patients
Summary
Lung cancer is the most common cause of cancer-related deaths worldwide. Approximately 85% of lung cancer cases are non-small-cell lung cancer (NSCLC) mainly including lung adenocarcinoma (Ade) accounting for nearly 40% of lung cancer and lung squamous cell carcinoma (SCC) accounting for about 30% of lung cancer [1, 2]. Standard chemotherapy and better supportive care have improved overall survival and life quality, prognosis of advanced NSCLC patients remains poor [3]. The poor prognosis is predominantly attributed to the fact that high proportion of patients has reached advanced stage once diagnosed [4]. It is important to investigate underlying mechanisms of lung tumorigenesis and tumor progression, as well as to identify potential prognostic biomarkers that could even be used as drug targets. Such investigation would provide appropriate early diagnostic methods, better prognosis and more effective individualized therapeutic strategies for lung cancer patients
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