The occurrence of HLA-I LOH is relevant to genomic instability
Consistent with previous studies, the occurrence of HLA-I LOH was relevant to an elevated TMB level (median TMB 6.72 vs. 5.76, p<0.0001, Fig.3A) (Anagnostou et al., 2020; McGranahan et al., 2017; Shim et al., 2020). In addition, the TMB level of patients with HLA-I LOH at all three loci was significantly higher than those with HLA-I LOH at only one locus (median TMB 7.68 vs. 6.72, p=0.027, Fig.3B). When distinguished by cancer types, significant differences were observed in Non-SqCC NSCLC, LUSC, STES and BRCA (p=0.009, p=0.021, p=0.029, p=0.049, respectively, Supplementary Figure 2). However, despite that MSI-H samples presented the highest incidence of TMB-H (identified as TMB≥10.56, Supplementary Figure 3C), the incidence of HLA-I LOH decreased in these samples (Supplementary Figure 3C), which suggested that the incidence of HLA-I LOH might have a non-linear relationship with TMB. In colorectal cancer, the HLA-I LOH incidence of MSS samples was significantly higher than that of MSI-H samples (61/130 [46.9%] of MSS vs. 3/17 [17.6%] of MSI-H, p=0.022, Fig.3C). Conformably, in patients with other cancer types (Non-SqCC NSCLC, LUSC, BRCA, STES, OV, KIPAN, PAAD, PRAD, UCEC, CESC, LIHC), the ratio was 485/967 [50.2%] of MSS vs. 5/20 [25%] of MSI-H, p=0.026, Fig.3D). The MSI status of the study cohort was listed in Supplementary Table 2.