The Genomic Features Of Chinese Cancer Patients Harboring Hla Loh.

Abstract HLA LOH is an immune escape mechanism subject to microenvironmental selection pressures in tumor evolution. In previous study, the prevalence of HLA LOH in Chinese cancer patients has been characterized. However, the genomic features of patients harboring HLA LOH remains unknown. Methods The sequencing data of 1021 cancer genes from 1504 advanced patients across 11 diverse cancer types was analyzed to investigate the internal relationship between HLA LOH and genomic alteration. Exon 2, exon 3, and bilateral introns of HLA-A/B/C genes were well covered in the 1021-gene panel. HLA LOH was analyzed using the LOHHLA algorithm. Results Consistent with previous study, we found that the occurrence of HLA LOH is related to genomic instability. In colorectal cancer, the HLA LOH ratio of MSS samples was significantly higher than that of MSI-H samples. Among the remaining 10 cancer types, the trend was consistent (Table 1). These results revealed that HLA LOH is a potential immune escape mechanism for MSS patients. In NSCLC and BRCA, HLA LOH is associated with an elevated TMB (p<0.001, p<0,05). The alteration frequency of TP53 and LRP1B in HLA LOH group was significantly higher than that in HLA stable group (p<0.001, p=0.005, respectively). The occurrence of HLA LOH is also related to alterations in several important signaling pathways. The alteration frequencies of RTK/RAS pathway, p53 pathway, Notch pathway, Hippo pathway and Nrf2 pathway in the HLA LOH group were significantly higher than that in HLA stable group. These results are indicating that HLA LOH may mediate tumorigenesis by interfering with normal signaling transduction. Conclusions and Discussion Statistical results revealed that the occurrence of HLA LOH was related to genomic instability, including high TMB level and alterations in oncogenic signaling pathways, which may facilitate tumor formation. Overall, these findings may provide useful information for clinical practice and immunotherapy. The correlation between MSI stage and HLA LOHCancer TypesMSIHLA LOHHLA stablePercent with HLA LOHP valueColorectal cancerMSS617146.2%0.025MSI-H31416.7%Remaining 10 cancer typesMSS48549949.3%0.031MSI-H51525.0% Citation Format: Jian Zhao, Jie Hu, Xiuqin Zhang, Xuan Gao, Fan Tong, Xiaorui Fu, Yuting Yi, Yanfang Guan, Xuefeng Xia, Jian'an Huang. The genomic features of Chinese cancer patients harboring HLA LOH [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1896.