The genomic alterations of lung adenocarcinoma and lung squamous cell carcinoma can explain the differences of their overall survival rates.

ABSTRACT

In the US, lung carcinoma accounted for over 150,000 deaths in 2018 and the advances in increasing survival rates are still limited. In this study, we investigated the cohorts with lung adenocarcinoma (LUAD) or lung squamous cell carcinoma (LUSC) from The Cancer Genome Atlas to figure out the risk factors and genomic alterations that affected their prognosis. The histoclinical factors that differed between LUAD and LUSC were identified and the risk factors affecting the overall survival were figured out for both LUAD and LUSC. Next, the patterns of nucleotides substitutions and the mutational signatures were extracted to illustrate whether different mutational processes performed for them. Finally, the genes that had different frequencies of mutation were identified. LUAD and LUSC presented differences in histoclinical factors including age at the time of diagnosis, sex, smoking history, pathological T classification, and overall survival. This was caused by the distinct genomic alterations including the transition-to-transversion ratios, mutational signatures, and the frequently mutated genes. We proposed that the mutational signature associated with aging could be used to predict the prognosis of patients with LUAD. On the other hand, the AID/APOBEC family was associated with the prognosis of LUSC. Finally, SNTG1 and LRRK2 might be important in LUAD and LUSC, respectively.