Laboratory of Translational Cancer Genomics, Biomedical Center,Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1665/76, 323 00, Pilsen, Czech Republic.
Laboratory of Cancer Treatment and Tissue Regeneration, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Prague, Czech Republic.
BMC Cancer. 2022 Aug 13;22(1):884. doi: 10.1186/s12885-022-09989-0.
Hepatocellular carcinoma (HCC) is a fatal disease characterized by early genetic alterations in telomerase reverse transcriptase promoter (TERTp) and β-catenin (CTNNB1) genes and immune cell activation in the tumor microenvironment. As a novel approach, we wanted to assess patient survival influenced by combined presence of mutations and densities of CD8+ cytotoxic T cells.
Tissue samples were obtained from 67 HCC patients who had undergone resection. We analysed CD8+ T cells density, TERTp mutations, rs2853669 polymorphism, and CTNNB1 mutations. These variables were evaluated for time to recurrence (TTR) and disease free survival (DFS).
TERTp mutations were found in 75.8% and CTNNB1 mutations in 35.6% of the patients. TERTp mutations were not associated with survival but polymorphism rs2853669 in TERTp was associated with improved TTR and DFS. CTNNB1 mutations were associated with improving TTR. High density of CD8+ T-lymphocytes in tumor center and invasive margin correlated with longer TTR and DFS. Combined genetic and immune factors further improved survival showing higher predictive values. E.g., combining CTNNB1 mutations and high density of CD8+ T-lymphocytes in tumor center yielded HRs of 0.12 (0.03-0.52), p = 0.005 for TTR and 0.25 (0.09-0.74), p = 0.01 for DFS.
The results outline a novel integrative approach for prognostication through combining independent predictive factors from genetic and immune cell profiles. However, larger studies are needed to explore multiple cell types in the tumor microenvironment.
肝细胞癌（HCC）是一种致命疾病，其特征是端粒酶逆转录酶启动子（TERTp）和β-连环蛋白（CTNNB1）基因的早期遗传改变，以及肿瘤微环境中的免疫细胞激活。作为一种新方法，我们希望评估突变和 CD8+细胞毒性 T 细胞密度综合存在对患者生存的影响。
从接受过切除术的 67 名 HCC 患者中获取组织样本。我们分析了 CD8+T 细胞密度、TERTp 突变、rs2853669 多态性和 CTNNB1 突变。这些变量用于评估无复发生存期（TTR）和无病生存期（DFS）。
75.8%的患者存在 TERTp 突变，35.6%的患者存在 CTNNB1 突变。TERTp 突变与生存无关，但 TERTp 中的 rs2853669 多态性与 TTR 和 DFS 的改善相关。CTNNB1 突变与 TTR 的改善相关。肿瘤中心和侵袭边缘高 CD8+T 淋巴细胞密度与较长的 TTR 和 DFS 相关。联合遗传和免疫因素进一步提高了生存率，显示出更高的预测值。例如，将 CTNNB1 突变与肿瘤中心高 CD8+T 淋巴细胞密度相结合，TTR 的 HR 为 0.12（0.03-0.52），p=0.005，DFS 的 HR 为 0.25（0.09-0.74），p=0.01。
这些结果概述了一种通过整合遗传和免疫细胞谱中的独立预测因子进行预后的新综合方法。然而，需要更大的研究来探索肿瘤微环境中的多种细胞类型。
