A retrospective study with whole-exome sequencing of tissue samples: analysis of risk factors in patients of persistent cough following lung segmentectomy

ABSTRACT

Persistent cough after pulmonary resection (CAP) is one of the most common postoperative complications in patients with non-small cell lung cancer (NSCLC) and can impair postoperative recovery and quality of life. While several clinical and surgical risk factors have been identified, the genetic basis of CAP remains unclear. Whole-exome sequencing (WES) allows comprehensive detection of coding-region mutations and may help uncover molecular markers associated with CAP. This retrospective cohort study investigated the association between gene mutations identified by WES and CAP in patients with NSCLC.Twenty NSCLC patients who underwent surgery were enrolled and categorized into a cough group (n=9) and a non-cough group (n=11) using the Leicester Cough Questionnaire-Mandarin Chinese version (LCQ-MC). Postoperative tissue samples were collected for WES. Clinical data were analyzed to assess the incidence of CAP and related clinical characteristics. Genetic mutations were identified through WES, and a logistic regression model was applied to determine potential risk factors for CAP.Chi-squared tests identified significant associations between CAP and preoperative cough, as well as mutations in the TBC1D2 and SEPT12 genes. No significant associations were observed for gender, comorbidities, family history of cancer, postoperative diagnosis, pleural invasion, pathological stage, pleural effusion, or pneumothorax. These findings may aid in identifying potential diagnostic markers and therapeutic targets for the management of postoperative cough.The TBC1D2 and SEPT12 genes were found to harbor both insertion/deletion (INDEL) and single nucleotide polymorphism (SNP) mutations in NSCLC patients who developed CAP after surgery. These genetic alterations may serve as potential predictive markers for postoperative CAP; however, given the small sample size, the findings should be regarded as hypothesis-generating and require validation in larger cohorts. Patients carrying multiple mutations appeared to have a higher likelihood of developing postoperative CAP.