Overview of HLA-I LOH events in Chinese pan-cancer patients
Among 1482 advanced pan-cancer patients, 45.6% (676/1482) were identified with LOH in at least one HLA-I locus (Fig.2B). The prevalence of HLA-I LOH presented considerable differences among cancer types, ranging from 12.2% (prostate adenocarcinoma) to 68.0% (cervical squamous cell carcinoma) (Fig.2C, Table 2), which was in accordance with previous studies that HLA-I LOH was more enriched in squamous cell carcinoma (68.0% in cervical squamous cell carcinoma, 62.2% in lung squamous cell carcinoma, Table 2) (Montesion et al., 2020). In NSCLC patients, there was an enrichment of HLA-I LOH in both early-stage (I-IIIa) LUSC patients (24/88 [27.3%] of LUAD vs. 26/42 [61.9%] of LUSC, p<0.001, Fig.2D) and advanced (IIIb-IV) LUSC patients (162/306 [52.9%] of LUAD vs. 156/251 [62.2%] of LUSC, p=0.029, Fig.2D), which was consistent with the results that HLA mutations occurred more frequently in LUSC (Shukla et al., 2015; McGranahan et al., 2017). However, in contrast to the enrichment of HLA-I LOH in advanced LUAD (24/88 [27.3%] of early-stage LUAD vs. 162/306 [52.9%] of advanced LUAD, p<0.001, Fig.2D), the incidence of HLA-I LOH between early-stage and advanced LUSC was equivalent (26/42 [61.9%] of early-stage LUSC vs. 156/251 [62.2%] of advanced LUSC, p=0.976, Fig.2D). In 43.3% (293/676) patients harboring HLA-I LOH, LOH co-occurred in HLA-A, B, and C (Fig.2E). The HLA-I gene status of HLA-I LOH patients in each cancer type was shown in Supplementary Figure 1.