Journal Article

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

Liu, Panpan, Wen, Shijun, Yang, Jing, Hou, Guo-Xin

2017

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Acute lymphoblastic leukemia / Adenocarcinoma / Adenocarcinoma - diagnosis / Adenocarcinoma - enzymology / Adenocarcinoma - mortality / Archaea / Biochemistry / Biology and Life Sciences / Biomarkers / Biomarkers, Tumor - genetics / Biomarkers, Tumor - metabolism / Breast cancer / Breast carcinoma / Cancer / Cancer therapies / Carcinoma, Squamous Cell - diagnosis / Carcinoma, Squamous Cell - enzymology / Carcinoma, Squamous Cell - mortality / Chemotherapy / Children / Chromosomes / Collaboration / Copy number / Cytotoxicity / Damage / Data Mining / Databases, Nucleic Acid / Deoxyribonucleic acid / Diagnosis / Differentiation / DNA / DNA repair / DNA topoisomerase / DNA Topoisomerases - genetics / DNA Topoisomerases - metabolism / Drugs / Eukaryotes / Gene Expression / Gene Expression Profiling / Genetic aspects / Genomes / Heterogeneity / Humans / Inhibitors / Isoenzymes / Isoforms / Kaplan-Meier Estimate / Laboratories / Leukemia / Lung cancer / Lung diseases / Lung Neoplasms - diagnosis / Lung Neoplasms - enzymology / Lung Neoplasms - mortality / Lungs / Lymph nodes / Lymphatic leukemia / Medical prognosis / Medical research / Medicine / Medicine and Health Sciences / Metabolism / Metastases / Mice / Mining / Mitochondrial DNA / Mitosis / Molecular biology / Non-small cell lung cancer / Non-small cell lung carcinoma / Oncology / Ovarian cancer / Ovarian carcinoma / Pathology / Patients / Paving / Pharmacology / Prognosis / Prostate cancer / Quality of life / Quantitation / Radiation therapy / Recombination / Replication / Ribonucleic acid / RNA / Squamous cell carcinoma / Stability / Strands / Studies / Supercoiling / Survival / Tissues / Topology / Toxicity / Tumor cells