Department of Gastroenterology, Jining First People's Hospital, Jining, China.
Department of Radiotherapy Oncology, The Affiliated Yancheng First Hospital of Nanjing University Medical School, The First People's Hospital of Yancheng, Yancheng, China.
Front Endocrinol (Lausanne). 2023 Mar 24;14:1153562. doi: 10.3389/fendo.2023.1153562. eCollection 2023.
Liver hepatocellular carcinoma (LIHC) is the seventh most commonly diagnosed malignancy and the third leading cause of all cancer death worldwide. The undifferentiated macrophages M0 can be induced into polarized M1 and M2 to exert opposite effects in tumor microenvironment. However, the prognostic value of macrophages M0 phenotype remains obscure in LIHC.
The transcriptome data of LIHC was obtained from TCGA database and ICGC database. 365 LIHC samples from TCGA database and 231 LIHC samples from ICGC database were finally included. Macrophages M0-related genes (MRGs) were screened by Pearson correlation analysis and univariate Cox regression analysis based on the infiltration level of Macrophages M0. LASSO regression analysis was employed to construct a prognostic signature based on MRGs, and risk scores were accordingly calculated. Then we investigated the MRGs-based prognostic signature with respects to prognostic value, clinical significance, strengthened pathways, immune infiltration, gene mutation and drug sensitivity. Furthermore, the expression pattern of MRGs in the tumor microenvironment were also detected in LIHC.
A ten-MRG signature was developed and clarified as independent prognostic predictors in LIHC. The risk score-based nomogram showed favorable capability in survival prediction. Several substance metabolism activities like fatty acid/amino acid metabolism were strengthened in low-risk group. Low risk group was deciphered to harbor TTN mutation-driven tumorigenesis, while TP53 mutation was dominant in high-risk group. We also ascertained that the infiltration levels of immune cells and expressions of immune checkpoints are significantly influenced by the risk score. Besides, we implied that patients in low-risk group may be more sensitive to several anti-cancer drugs. What's more important, single-cell analysis verified the expression of MRGs in the tumor microenvironment of LIHC.
Multidimensional evaluations verified the clinical utility of the macrophages M0-related gene signature to predict prognosis, assist risk decision and guide treatment strategy for patients with LIHC.
肝肝细胞癌（LIHC）是全球第七种最常见的恶性肿瘤，也是所有癌症死亡的第三大主要原因。未分化的巨噬细胞 M0 可以被诱导为极化的 M1 和 M2，在肿瘤微环境中发挥相反的作用。然而，巨噬细胞 M0 表型在 LIHC 中的预后价值仍不清楚。
从 TCGA 数据库和 ICGC 数据库中获取 LIHC 的转录组数据。最终纳入 TCGA 数据库的 365 个 LIHC 样本和 ICGC 数据库的 231 个 LIHC 样本。基于巨噬细胞 M0 的浸润水平，通过 Pearson 相关分析和单因素 Cox 回归分析筛选巨噬细胞 M0 相关基因（MRGs）。利用 LASSO 回归分析构建基于 MRGs 的预后特征，并据此计算风险评分。然后，我们从预后价值、临床意义、增强途径、免疫浸润、基因突变和药物敏感性等方面对基于 MRGs 的预后特征进行了研究。此外，还检测了 LIHC 肿瘤微环境中 MRGs 的表达模式。
构建并验证了一个由十个 MRGs 组成的独立预后预测因子，用于 LIHC。基于风险评分的列线图在生存预测方面表现出良好的能力。在低风险组中，几种物质代谢活动（如脂肪酸/氨基酸代谢）得到了加强。低风险组揭示了 TTN 突变驱动的肿瘤发生，而高风险组则以 TP53 突变为主要特征。我们还确定了免疫细胞的浸润水平和免疫检查点的表达受到风险评分的显著影响。此外，我们暗示低风险组的患者可能对几种抗癌药物更敏感。更重要的是，单细胞分析验证了 LIHC 肿瘤微环境中 MRGs 的表达。
多维度评估验证了巨噬细胞 M0 相关基因特征预测预后、辅助风险决策和指导 LIHC 患者治疗策略的临床实用性。
