Smoking alters the evolutionary trajectory of non‑small cell lung cancer

Yu,Xiao‑Jun; Yu,Xiao‑Jun; Chen,Gang; Chen,Gang; Yang,Jun; Yang,Jun; Yu,Guo‑Can; Yu,Guo‑Can; Zhu,Peng‑Fei; Zhu,Peng‑Fei; Jiang,Zheng‑Ke; Jiang,Zheng‑Ke; Feng,Kan; Feng,Kan; Lu,Yong; Lu,Yong; Bao,Bin; Bao,Bin; Zhong,Fang‑Ming; Zhong,Fang‑Ming

doi:10.3892/etm.2019.7958

Smoking alters the evolutionary trajectory of non‑small cell lung cancer

Authors:
- Xiao‑Jun Yu
- Gang Chen
- Jun Yang
- Guo‑Can Yu
- Peng‑Fei Zhu
- Zheng‑Ke Jiang
- Kan Feng
- Yong Lu
- Bin Bao
- Fang‑Ming Zhong
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Affiliations: Department of Thoracic Surgery, The First People's Hospital of Fuyang Hangzhou, Hangzhou, Zhejiang 311400, P.R. China, Department of Thoracic Surgery, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang 310003, P.R. China, Department of Surgery, Hangzhou Fuyang Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang 311400, P.R. China
Published online on: August 29, 2019 https://doi.org/10.3892/etm.2019.7958
Pages: 3315-3324
Copyright: © Yu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Smoking is the biggest risk factor for lung cancer. Smokers have a much higher chance of developing lung tumors with a worse survival rate; however, non‑smokers also develop lung tumors. A number of questions remain including the underlying difference between smoker and non‑smoker lung cancer patients and the involvement of genetic and epigenetic processes in tumor development. The present study analyzed the mutation data of 100 non‑small cell lung cancer (NSCLC) patients, 12 non‑smokers, 48 ex‑smokers and 40 smokers, from Tracking Non‑Small Cell Lung Cancer Evolution through Therapy Consortium. A total of 68 genes exhibited different mutation patterns across non‑smokers, ex‑smokers and smokers. A number of these 68 genes encode membrane proteins with biological regulation, metabolic process, and response to stimulus functions. For each group of patients, the top 10 most frequently mutated genes were selected and their oncogenetic tree inferred, which reflected how the genes evolve during tumor genesis. By comparing the oncogenetic trees of non‑smokers and smokers, it was identified that in non‑smokers, the mutation of epidermal growth factor receptor (EGFR) was an early genetic alteration event and EGFR was the key driver, but in smokers, the mutation of titin (TTN) was more important. Based on network analysis, TTN can interact with spectrin α erythrocytic 1 through calmodulin 2 and troponin C1. These genetic differences during tumorigenesis of non‑smoker and smoker lung cancer patients provided novel insights into the effects of smoking on the evolutionary trajectory of non‑small cell lung cancer and may prove helpful for targeted therapy of different lung cancer subtypes.

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