Association of pre-existing conditions with major driver mutations and PD-L1 expression in NSCLC.

Objectives: This study aims to explore how pre-existing conditions such as blood types, family history of cancer and comorbid diseases correlate with the genetic and programmed death-ligand 1 (PD-L1) expression that contributes to the heterogeneous biological behaviours of non-small cell lung cancer (NSCLC).

Materials and methods: A cohort of 5507 NSCLC patients who underwent surgical resection between January 2014 and July 2018 was studied. Targeted next-generation sequencing was used to detect mutations in nine pivotal cancer-related genes, and immunohistochemical staining was applied to assess PD-L1 expression. Logistic regression analysis was employed to identify significant correlations.

Results: All patients underwent NGS, with 1839 were also evaluated for PD-L1 expression. Several significant findings were found: ROS1 mutations were closely associated with a family history of lung cancer (OR 7.499, 95% CI 1.094 to 30.940, p=0.013). Epidermal growth factor receptor (EGFR) L858R mutations were common among patients with a family history of non-lung cancers and those with hypertension (OR 2.089, 95% CI 1.029 to 4.135, p=0.037 and OR 1.252, 95% CI 1.001 to 1.562, p=0.048, respectively). Pre-existing conditions such as diabetes and hepatitis B surface antigen positivity (OR 1.468, 95% CI 1.042 to 2.047, p=0.026 and OR 1.373, 95% CI 1.012 to 1.847, p=0.038, respectively) were correlated with EGFR exon 19 deletions. RhD negativity showed potential ties to BRAF mutations (OR 0.010, 95% CI 0.001 to 0.252, p=0.001). A history of tuberculosis linked to increased PD-L1 expression in immune cells (OR 3.597, 95% CI 1.295 to 14.957, p=0.034).

Conclusion: This large-scale, cross-sectional study reveals a complex interplay between genetic mutations, immunological features and pre-existing conditions in NSCLC patients, offering insights that could inform personalised treatment strategies.