Thirdhand Smoke May Promote Lung Adenocarcinoma Development through HN1

Thirdhand smoke (THS) refers to residual tobacco smoking pollutants that can be adsorbed to indoor surfaces and dust and persist for years after active smoking. THS-related chemicals such as N-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are tobacco-specific lung carcinogens that involved in lung cancer development and progression. In this study, we computed the differentially expressed genes (DEGs) between THS and paired control samples. THS-related overexpressed genes (OEs) were overlapped with OEs of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Survival analyses of these overlapped genes were performed using LUAD and LUSC data. 6 genes were selected for validation based on their expression levels and prognostic value. Hematological and neurological expressed 1 (HN1) was further selected due to its novelty in LUAD research. The potential roles of HN1 in LUAD were explored in several ways. In summary, HN1 is overexpressed in THS samples and is associated with the prognosis of patients with LUAD. It may promote cancer progression through several pathways and could serve as a potential therapeutic target especially for THS-related LUAD. In-depth mechanistic studies and clinical trials are warranted.