Clinical characteristics and gene mutation profiles of chronic obstructive pulmonary disease in non-small cell lung cancer

Lin Yuan; Ting Guo; Chengping Hu; Wei Yang; Xiaoli Tang; Hao Cheng; Yang Xiang; Xiangping Qu; Huijun Liu; Xiaoqun Qin; Ling Qin; Chi Liu

doi:10.3389/fonc.2022.946881

Clinical characteristics and gene mutation profiles of chronic obstructive pulmonary disease in non-small cell lung cancer

Front Oncol. 2022 Oct 4:12:946881. doi: 10.3389/fonc.2022.946881. eCollection 2022.

Authors

Lin Yuan^{1

2

3}, Ting Guo⁴, Chengping Hu^{1

5}, Wei Yang^{1

5}, Xiaoli Tang⁶, Hao Cheng^{7

8}, Yang Xiang², Xiangping Qu², Huijun Liu², Xiaoqun Qin², Ling Qin^{1

5}, Chi Liu^{1

2

3}

Affiliations

¹ Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, China.
² Department of Physiology, School of Basic Medicine Science, Central South University, Changsha, China.
³ Basic and Clinical Research Laboratory of Major Respiratory Diseases, Central South University, Changsha, China.
⁴ Department of Respiratory Medicine, The First Hospital of Changsha, Changsha, China.
⁵ National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, China.
⁶ Pulmonary and Critical Care Medicine, Huaihua Tumor Hospital, Huaihua, China.
⁷ Department of Radiotherapy, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China.
⁸ Department of Nasopharyngeal Carcinoma, The First People's Hospital of Chenzhou, Chenzhou, China.

Abstract

Purpose: The coexistence of chronic obstructive pulmonary disease (COPD) often leads to a worse prognosis in patients with non-small cell lung cancer (NSCLC). Meanwhile, approaches targeting specific genetic alterations have been shown to significantly improve the diagnosis and treatment outcomes of patients with NSCLC. Herein, we sought to evaluate the impact of COPD on the clinical manifestations and gene mutation profiles of NSCLC patients with both circulating tumor (ctDNA) and tumor DNA (tDNA).

Materials and methods: The influence of COPD on clinical features was observed in 285 NSCLC cohorts suffering from NSCLC alone, NSCLC coexisting with COPD, or NSCLC coexisting with prodromal changes in COPD (with emphysema, bullae, or chronic bronchitis). The gene mutation profiles of specific 168 NSCLC-related genes were further analyzed in the NSCLC sub-cohorts with formalin-fixed and paraffin-embedded tumor DNA (FFPE tDNA) samples and plasma circulating tumor DNA (PLA ctDNA) samples. Moreover, mutation concordance was assessed in tDNA and paired ctDNA of 110 NSCLC patients.

Results: Relative to patients with NSCLC alone, patients with NSCLC coexisting with COPD and prodromal changes presented with worse lung functions, more clinical symptoms, signs and comorbidities, and inconsistent gene mutation profiles. In addition, patients in the latter two groups exhibited a higher average frequency of gene mutation. Lastly, mutation concordance between tDNA and ctDNA samples was significantly reduced in NSCLC patients coexisting with COPD.

Conclusions: Collectively, our findings revealed that coexistence of COPD leads to worse clinical manifestations and altered gene mutation profiles in patients with NSCLC. Additionally, for NSCLC patients with COPD, the use of ctDNA instead of tDNA may not be the most efficient approach to identifying gene mutations.

Keywords: NSCLC-related genes; chronic obstructive pulmonary disease; circulating tumor DNA; non-small cell lung cancer; tumor DNA.