Bioinformatics-Based Identification of HDAC Inhibitors as Potential Drugs to Target EGFR Wild-Type Non-Small-Cell Lung Cancer
JournalFrontiers in Oncology
PublisherFrontiers Media S.A.
MetadataShow full item record
AbstractPatients with EGFR-mutant non-small-cell lung cancer (NSCLC) greatly benefit from EGFR-tyrosine kinase inhibitors (EGFR-TKIs) while the prognosis of patients who lack EGFR-sensitive mutations (EGFR wild type, EGFR-WT) remains poor due to a lack of effective therapeutic strategies. There is an urgent need to explore the key genes that affect the prognosis and develop potentially effective drugs in EGFR-WT NSCLC patients. In this study, we clustered functional modules related to the survival traits of EGFR-WT patients using weighted gene co-expression network analysis (WGCNA). We used these data to establish a two-gene prognostic signature based on the expression of CYP11B1 and DNALI1 by combining the least absolute shrinkage and selection operator (LASSO) algorithms and Cox proportional hazards regression analysis. Following the calculation of risk score (RS) based on the two-gene signature, patients with high RSs showed a worse prognosis. We further explored targeted drugs that could be effective in patients with a high RS by the connectivity map (CMap). Surprisingly, multiple HDAC inhibitors (HDACis) such as trichostatin A (TSA) and vorinostat (SAHA) that may have efficacy were identified. Also, we proved that HDACis could inhibit the proliferation and metastasis of NSCLC cells in vitro. Taken together, our study identified prognostic biomarkers for patients with EGFR-WT NSCLC and confirmed a novel potential role for HDACis in the clinical management of EGFR-WT patients. Copyright 2021 Wang, Zheng, Lu, Wang, Cheng, Chen, Hou, Qi, Liu, Che and Hu.
SponsorsThis study was supported by the National Natural Science Foundation of China (Grant No. 81972197;No. 81472193), the Key Research and Development Program of Liaoning Province (2018225060), the Natural Science Foundation of Liaoning Province (2019-ZD-777), the Technological Special Project of Liaoning Province of China (2019020176-JH1/103), the Science and Technology Plan Project of Liaoning Province (No. 2013225585), Science and Technology Plan Project of Shenyang City (19-112-4-099).
KeywordEGFR wild type
histone deacetylase inhibitor
non-small cell lung cancer
Identifier to cite or link to this itemhttp://hdl.handle.net/10713/15192