Mining expression and prognosis of topoisomerase isoforms in non-small-cell lung cancer by using Oncomine and Kaplan-Meier plotter

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.

Fig 1. Topoisomerase family genes analysis in lung Adenocarcinoma (Ade) and Squamous Cell lung Carcinoma (SCC) (Oncomine database).

Figures were derived from gene expression data in Oncomine comparing expression levels of topoisomerase family genes in normal (left plot) and cancer tissue (right plot) and plotted using Graphpad Prism software. Y-axis represents the median intensity, 10th and 90th percentile data. (A) Comparison of TOP1 mRNA expression in Ade. (B) Comparison of TOP1 mRNA expression in SCC. (C) Comparison of TOP1MT mRNA expression in Ade. (D) Comparison of TOP1MT mRNA expression in SCC. (E) Comparison of TOP2A mRNA expression in Ade. (F) Comparison of TOP2A mRNA expression in SCC. (G) Comparison of TOP3A mRNA expression in Ade.

Fig 2. The prognostic value of TOP1 expression.

(A) Survival curves were plotted for all NSCLC patients (n = 1726). (B) Survival curves were plotted for Ade patients (n = 591). (C) Survival curves were plotted for SCC patients (n = 492). Data was analyzed using Kaplan-Meier Plotter. Patients with expression above the median are indicated in red line, and patients with expressions below the median in black line. HR means hazard ratio.

Fig 3. The prognostic value of TOP1MT expression.

(A) Survival curves were plotted for all NSCLC patients (n = 984). (B) Survival curves were plotted for Ade patients (n = 549). (C) Survival curves were plotted for SCC patients (n = 239). Data was analyzed using Kaplan-Meier Plotter. Patients with expression above the median are indicated in red line, and patients with expressions below the median in black line. HR means hazard ratio.

Fig 4. The prognostic values of TOP2A expression.

(A) Survival curves were plotted for all NSCLC patients (n = 1726). (B) Survival curves were plotted for Ade patients (n = 591). (C) Survival curves were plotted for SCC patients (n = 492). Data was analyzed using Kaplan-Meier Plotter. Patients with expression above the median are indicated in red line, and patients with expressions below the median in black line. HR means hazard ratio.

Fig 5. The prognostic value of TOP2B expression.

(A) Survival curves were plotted for all NSCLC patients (n = 1726). (B) Survival curves were plotted for Ade patients (n = 591). (C) Survival curves were plotted for SCC patients (n = 492). Data was analyzed using Kaplan-Meier Plotter. Patients with expression above the median are indicated in red line, and patients with expressions below the median in black line. HR means hazard ratio.

Fig 6. The prognostic value of TOP3A expression.

(A) Survival curves were plotted for all NSCLC patients (n = 1726). (B) Survival curves were plotted for Ade patients (n = 591). (C) Survival curves were plotted for SCC patients (n = 492). Data was analyzed using Kaplan-Meier Plotter. Patients with expression above the median are indicated in red line, and patients with expressions below the median in black line. HR means hazard ratio.

Fig 7. The prognostic value of TOP3B expression.

(A) Survival curves were plotted for all NSCLC patients (n = 1726). (B) Survival curves were plotted for Ade patients (n = 591). (C) Survival curves were plotted for SCC patients (n = 492). Data was analyzed using Kaplan-Meier Plotter. Patients with expression above the median are indicated in red line, and patients with expressions below the median in black line. HR means hazard ratio.