Alterations of multiple oncogenic signaling pathways are enriched in HLA-I LOH patients
We further analyzed the alteration frequencies of DDR pathways and 10 canonical oncogenic signaling pathways in advanced pan-cancer cohort. A signaling pathway was considered as altered if one or more genes in this pathway have non-synonymous mutations (Sanchez-Vega et al., 2018). The alteration frequencies of CPF pathway, FA pathway, p53 pathway, RTK/RAS pathway, Notch pathway, Hippo pathway and Nrf2 pathway in the HLA-I LOH group were significantly higher than that in HLA-I stable group (p<0.0001, p=0.023, p<0.0001, p<0.0001, p=0.032, p=0.013, p=0.003, respectively). Among these signaling pathways, the CPF pathway, p53 pathway and RTK/RAS pathway were most frequently mutated in the study cohort, in which the differences between the HLA-I LOH group and HLA-I group were the most significant (Fig.4A, Fig.4B). Consistent result was obtained in the NSCLC cohort, where the most frequently altered pathways had the most significant differences between groups (p53 pathway in LUSC and RTK/RAS pathway in Non-SqCC NSCLC, Supplementary Figure 4A, Supplementary Figure 4B).