Integrative bioinformatic analysis of p53 and pathway alterations in two different lung cancer subtypes

Abstract

Whether p53, either wild type (WT) or mutant, plays cell-specific or uniform role remains controversial. Using The Cancer Genome Atlas, we examined p53 in the lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), two lung cancers with different cellular origins and frequent p53 mutation (52% and 83%, respectively). Mutant p53 more strongly correlates with different genomic alteration and protein expression profiles in LUAD than in LUSC. p53 mutation in LUAD and LUSC is associated with multiple exacerbated clinical outcomes. Although the presence of p53 mutation does not change the survival of LUAD patients, LUSC patients containing p53 mutation exhibit surprisingly prolonged survivals. Ingenuity Pathway Analyses with genes co-expressed with WT or mutant p53 in both LUAD and LUSC show that mutant p53 in these two cancers are correlated with different signaling. Additionally, WT p53 in LUAD are largely associated with activation of tumor suppressive pathways and suppression of the tumor promotive ones, a pattern different from what is observed for WT p53 in LUSC. Furthermore, pathway analyses of genes differentially expressed between cancers with mutant and WT p53 for both LUAD and LUSC revealed different pathway fashions for these two cancers. Our study indicates that both WT and mutant p53 may have cell-specific functions, which needs to be validated with future experimental investigations.