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.