Abstract 2739: ARID1A deficiency in HBV related hepatocarcinoma patients is associated with upregulated immune activity
Authors: Tao Xing, Han Wang, Xiaosong Rao, Guilan Dong, Xuan Gao, Yaping Xu, Xuefeng Xia, Yanfang Guan, Yiran Chen, Jing Zhao, Jun Liang, Li Li, Zhenping Wen
Journal: Cancer Research (2021)

Abstract Background: As the function of ARID1A loss is controversial in liver cancer, we aim to elucidate how this most frequently mutated SWI/SNF gene would affect the biological process in patients with HBV related hepatocarcinoma, a common type of liver cancer in China, and enlighten the therapy strategies. Methods: Mutation and survival data of 425 HBV patients from three cohorts (TCGA-LIHC, AMC, CHCC) was integrated to assess the Tumor mutational burden (TMB), mutation pattern and OS between ARID1A deficiency patients and normal patients. Single-sample gene set enrichment analysis and Wilcox test were performed with expression data from CHCC-HBV patients for immune signatures and genes associated with ARID1A deficiency. Results: The most frequently loss of function mutation or deletion in ARID1A would lead to deficiency in liver cancer patients. We found that EMT and cell cycle related pathway are enriched. In addition, Mesenchymal marker genes were highly expressed in ARID1A deficiency group. These results revealed that ARID1A deficiency is associated with invasion which corresponded to the worse overall survival. However, these HBV-HCC patients with ARID1A loss may have better response to immunotherapy as the TMB was higher in the ARID1A deficiency group as well as the mutation rate in base excision repair pathway which represent an unstable status in the genome. Investigation showed that immune infiltration level, including the CD8 T cell, Cytotoxic cells (Table 1) was increased in ARID1A deficiency group. Meanwhile, the expression of immune checkpoint gene TIM3 were significantly higher in ARID1A loss patients. Conclusion: ARID1A deficiency defined a group of HBV related liver cancer patients who had worse outcome due to promotion in cell migration. However, the higher TMB, higher mutation rate in DNA damage pathway, higher expression of TIM3 and upregulated immune activity suggested that they might be beneficial target for immunotherapy. p value between the ARID1A deficiency group and normal groupImmune infiltration levelCD8 T cells0.037Immune infiltration levelNeutrophils0.029Immune infiltration leveliDC0.045Immune infiltration levelDC0.024Immune infiltration levelCytotoxic cells0.035Immune infiltration levelTgd cells0.036Immune infiltration levelTreg cells0.041Immune infiltration levelM1 macrophage0.024Immune infiltration levelAll immune0.044GSEA for hallmark pathwayE2F_TARGETS0.006GSEA for hallmark pathwayTNFA_SIGNALING_VIA_NFKB&amp;lt;0.001GSEA for hallmark pathwayINFLAMMATORY_RESPONSE&amp;lt;0.001GSEA for hallmark pathwayTGF_BETA_SIGNALING0.017mRNA expressionTIM30.04mRNA expressionIL60.0015mRNA expressionIFNG0.068MutationTMB0.01 Citation Format: Tao Xing, Han Wang, Xiaosong Rao, Guilan Dong, Xuan Gao, Yaping Xu, Xuefeng Xia, Yanfang Guan, Yiran Chen, Jing Zhao, Jun Liang, Li Li, Zhenping Wen. ARID1A deficiency in HBV related hepatocarcinoma patients is associated with upregulated immune activity [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 2739.