1. Academic Validation
  2. Bioinformatics-Based Identification of HDAC Inhibitors as Potential Drugs to Target EGFR Wild-Type Non-Small-Cell Lung Cancer

Bioinformatics-Based Identification of HDAC Inhibitors as Potential Drugs to Target EGFR Wild-Type Non-Small-Cell Lung Cancer

  • Front Oncol. 2021 Mar 8;11:620154. doi: 10.3389/fonc.2021.620154.
Yizhe Wang 1 Chunlei Zheng 2 3 4 Wenqing Lu 2 3 4 Duo Wang 2 3 4 Yang Cheng 1 Yang Chen 1 Kezuo Hou 2 3 4 Jianfei Qi 5 Yunpeng Liu 2 3 4 Xiaofang Che 2 3 4 Xuejun Hu 1
Affiliations

Affiliations

  • 1 Department of Respiratory and Infectious Disease of Geriatrics, The First Hospital of China Medical University, Shenyang, China.
  • 2 Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.
  • 3 Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China.
  • 4 Liaoning Province Clinical Research Center for Cancer, Shenyang, China.
  • 5 Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, Baltimore, MD, United States.
Abstract

Patients 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.

Keywords

EGFR wild type; WGCNA; histone deacetylase inhibitor; metastasis; non-small cell lung cancer; proliferation.

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