Research Paper Volume 12, Issue 7 pp 5878—5893
Survival-associated alternative splicing signatures in non-small cell lung cancer
- 1 Department of Medical Oncology, the Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266003, China
- 2 Department of Thoracic Surgery, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266003, China
- 3 Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266071, China
Received: July 25, 2019 Accepted: March 24, 2020 Published: April 13, 2020
https://doi.org/10.18632/aging.102983How to Cite
Copyright © 2020 Zhao et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Alternative splicing (AS) is fundamental to transcriptome and proteome richness, and data from recent studies suggested a critical association between AS and oncogenic processes. To date, no systematic analysis has been conducted on AS from the perspective of different sexes and subtypes in non-small-cell lung cancer (NSCLC). Thus, we integrated the information of NSCLC patients from The Cancer Genome Atlas (TCGA) and evaluated AS profiles from the perspectives of sex and subtype. Eventually, a total of 813 and 1020 AS events were found to be significantly related to the overall survival (OS) of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) patients. Four prognostic prediction models performed well at 1, 3, and 5 years, with an area under the receiver operating characteristic (ROC) curve (AUC) greater than 0.75. Notably, we explored the upstream splicing factors (SFs) and downstream regulatory mechanisms of the OS-associated AS events and verified four differentially expressed alternative splicing (DEAS) events via qPCR. These findings can provide important guidance for subsequent studies. In addition, we also constructed nomograms to facilitate early screening by clinicians and to determine patient outcomes in NSCLC.