Table_2_Aging-related features predict prognosis and immunotherapy efficacy in hepatocellular carcinoma.xls

The aging microenvironment serves important roles in cancers. However, most studies focus on circumscribed hot spots such as immunity and metabolism. Thus, it is well ignored that the aging microenvironment contributes to the proliferation of tumor. Herein, we established three prognosis-distinctive aging microenvironment subtypes, including AME1, AME2, and AME3, based on aging-related genes and characterized them with “Immune Exclusion,” “Immune Infiltration,” and “Immune Intermediate” features separately. AME2-subtype tumors were characterized by specific activation of immune cells and were most likely to be sensitive to immunotherapy. AME1-subtype tumors were characterized by inhibition of immune cells with high proportion of Catenin Beta 1 (CTNNB1) mutation, which was more likely to be insensitive to immunotherapy. Furthermore, we found that CTNNB1 may inhibit the expression of C-C Motif Chemokine Ligand 19 (CCL19), thus restraining immune cells and attenuating the sensitivity to immunotherapy. Finally, we also established a robust aging prognostic model to predict the prognosis of patients with hepatocellular carcinoma. Overall, this research promotes a comprehensive understanding about the aging microenvironment and immunity in hepatocellular carcinoma and may provide potential therapeutic targets for immunotherapy.

衰老的微环境在癌症的发生发展中扮演着至关重要的角色。然而，大多数研究仅关注免疫和代谢等局限性的热点区域。因此，衰老微环境对肿瘤增殖的促进作用常被忽视。本研究基于与衰老相关的基因，建立了三种预后特征不同的衰老微环境亚型，包括AME1、AME2和AME3，并分别以“免疫排斥”、“免疫浸润”和“免疫中间态”为特征进行表征。AME2亚型肿瘤表现为免疫细胞的特异性激活，最有可能对免疫治疗敏感。AME1亚型肿瘤则以免疫细胞的抑制为特征，其中Catenin Beta 1（CTNNB1）突变比例较高，更可能对免疫治疗不敏感。此外，我们发现CTNNB1可能抑制C-C基序趋化因子配体19（CCL19）的表达，从而抑制免疫细胞并降低对免疫治疗的敏感性。最终，我们还建立了一个稳健的衰老预后模型，用于预测肝细胞癌患者的预后。总体而言，本研究深化了对肝细胞癌中衰老微环境和免疫机制的综合理解，并可能为免疫治疗提供潜在的靶点。