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.