Relationship of liver cancer with LRP1B or TP53 mutation and tumor mutation burden and survival.

person Longrong Wang Liver Surgery Department, Shanghai Cancer Center, Shanghai, China info_outline Longrong Wang, Kai Yan, Jiamin Zhou, Ning Zhang, Miao Wang, Jia Song, Jing Zhao, Yuzi Zhang, Shangli Cai, Yiming Zhao, Lu Wang

Authors person Longrong Wang Liver Surgery Department, Shanghai Cancer Center, Shanghai, China info_outline Longrong Wang, Kai Yan, Jiamin Zhou, Ning Zhang, Miao Wang, Jia Song, Jing Zhao, Yuzi Zhang, Shangli Cai, Yiming Zhao, Lu Wang Organizations Liver Surgery Department, Shanghai Cancer Center, Shanghai, China, Fifth Department of Liver Surgery, Shanghai Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China, The Medical Department, 3D Medicines Inc., Shanghai, China Abstract Disclosures Research Funding Other Foundation Background: Liver cancer (LC), one of the most common causes of cancer-related deaths, is a serious medical problem due to the limited treatment options available for this disease. Immune checkpoint inhibitors (ICIs) that are proved to be beneficial in the treatment of advanced LC. Similar to observations in other cancers, these ICIs as monotherapy may benefit only a fraction of HCC patients. Tumor mutation burden (TMB) is an important predictor for efficacy of ICIs in several solid tumors. However, the research on exploring the association between TMB and mutant genes with high frequency of liver cancer is limited. Besides, previous research on prognostic factors primarily focus on pathological features, probing the effects of genetic variations are urgently needed to study. Methods: Whole-exome sequencing data of 377 liver tumors from the Cancer Genome Altas (TCGA) and next generation sequencing (NGS) data of 655 liver tumors from Chinese clinical dataset were analyzed to explore the associated between LRP1B or TP53 gene alteration and TMB. TMB was defined as total number of somatic non-synonymous mutations in coding region. Results: In total, 9.3% (35/377) of hepatic tumors in TCGA and 7.8% (51/655) in clinical cohort harboring LRP1B mutation. LRP1B mutation was significantly associated with higher TMB in both TCGA cohort (P = 0.0003) and clinical cohort (P = 0.0005). The frequency of TP53 mutation was 28.1% (106/377) in TCGA cohort, however, TP53 mutation represented a greater rate of 54.5% (357/655) in Chinese clinical cohort. TP53 mutation was also associated with higher TMB in the two cohort (P = 0.0005 for the TCGA cohort and P = 0.0010 for the clinical cohort). In addition, prognosis analysis was performed on patients in TCGA cohort. LRP1B statue resulted in significantly shorter overall survival (OS, median, 20.9 vs 61.7 months; HR, 2.22; P = 0.0012), and a decreasing trend on progression-free survival (PFS) without significant difference (median, 8.7 vs 16.6 months; HR, 1.28; P = 0.2839). TP53 mutation was an independent risk factors affecting both OS (HR 1.58, P = 0.0109) and PFS (HR 1.59, P = 0.0027), respectively. Conclusions: The results indicated that LRP1B or TP53 mutation was a poor prognostic factor in LC, and patients harboring any of these two gene mutations might easily benefit from the immunotherapy.