Histologic hallmarks of smoking in the Gauting lung adenocarcinoma donors cohort

The Gauting lung adenocarcinoma donors cohort already established that the age and lung functions influence patients´ survival (1). Here, we conducted a retrospective, exploratory combination of clinical information with tumor tissue profiles in 200 patients of this cohort. Relevant tumor mutations (KRAS, EGFR, p53, and NF1), tissue profiling (angiogenesis, inflammation, apoptosis and proliferation rates) were quantified for all patients. Then, 100 patients were randomly selected for a training sub-cohort. Mutation status, tissue profiling and clinical variables (age, sex, body mass index, lung functions, TNM descriptors, tumor location, and histology) were analyzed for correlation with the smoking status. The tumors from smokers positively correlate with KRAS mutation, high body mass index, and proliferation. They also negatively correlate with EGFR and p53 mutations, high lung functions, and angiogenesis. In the training sub-cohort, these variables can discriminate the smoking status of 88% tumors. Those variables were used to analyze a second sub-cohort of 100 other patients and were able to identify the smoking status in 86 percent of the cases. In conclusion, we identified an association of molecular biomarkers and clinical variables that highlight novel tumor genome‐phenome links. This association also discriminates the smoking status of tumors indicating two distinct pathways of carcinogenesis evolution in the lungs. (1)    Klotz LV, et al. Comprehensive clinical profiling of the Gauting locoregional lung adenocarcinoma donors. Cancer Med. 2019 Apr;8(4):1486-1499.