Disentangling Links Between Lung Cancer and Infectious Pneumonia via Real-World Data and Integrative Genomics.
PMID: 41624060 https://pubmed.ncbi.nlm.nih.gov/41624060
Abstract
Lung cancer (LC) patients frequently develop infectious pneumonia, often leading to suspension of anticancer therapy, yet the impact of LC on pneumonia progression remains unclear. This study employed a multidimensional approach to investigate whether LC constitutes a critical factor contributing to pulmonary infection onset and adverse short-term outcomes. Data from two intensive care unit databases were analyzed to assess the association between LC and pneumonia incidence and prognosis from a real-world perspective, with Mendelian randomization (MR) applied to validate causality. Additionally, post-GWAS analyses were conducted to explore comorbidity interaction patterns and potential shared therapeutic targets. Cross-sectional and cohort analyses identified LC as an independent risk factor for infectious pneumonia development and 28-day mortality, findings corroborated by sensitivity analyses across multiple models and datasets. Meta-analysis of MR results demonstrated causal relationships between genetically predicted LC and both pneumonia risk (OR = 1.103, 95% CI: 1.031-1.181, = 0.004) and short-term mortality (OR = 1.219, 95% CI: 1.100-1.350, < 0.001), with consistency across histological subtypes. After adjustment for comorbidities including chronic obstructive pulmonary disease (COPD), LC retained independent effects, while a strong LC-COPD genetic correlation was observed. Subgroup and mediation analyses revealed a two-way interplay between LC and COPD in driving pneumonia progression. Drug-target analyses suggested that modulation of the complement and coagulation cascades may benefit pneumonia patients with comorbid LC or COPD, highlighting , , and as key candidates and pointing to monocyte-centered pathways as promising therapeutic directions. These findings indicate that infection-related pulmonary inflammation in LC patients may be partly tumor-driven, challenging routine cessation of anticancer therapy and underscoring the need for comorbidity-oriented treatment strategies.
