Colorectal and Anal Surgery Department, General Surgery Center, First Hospital of Jilin University, Changchun, Jilin, China.
Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians University, Munich, Germany.
Front Immunol. 2023 Jul 27;14:1237350. doi: 10.3389/fimmu.2023.1237350. eCollection 2023.
Hepatocellular carcinoma (HCC) represents a prominent gastrointestinal malignancy with a grim clinical outlook. In this regard, the discovery of novel early biomarkers holds substantial promise for ameliorating HCC-associated mortality. Efferocytosis, a vital immunological process, assumes a central position in the elimination of apoptotic cells. However, comprehensive investigations exploring the role of efferocytosis-related genes (EFRGs) in HCC are sparse, and their regulatory influence on HCC immunotherapy and targeted drug interventions remain poorly understood.
RNA sequencing data and clinical characteristics of HCC patients were acquired from the TCGA database. To identify prognostically significant genes in HCC, we performed the limma package and conducted univariate Cox regression analysis. Subsequently, machine learning algorithms were employed to identify hub genes. To assess the immunological landscape of different HCC subtypes, we employed the CIBERSORT algorithm. Furthermore, single-cell RNA sequencing (scRNA-seq) was utilized to investigate the expression levels of ERFGs in immune cells and to explore intercellular communication within HCC tissues. The migratory capacity of HCC cells was evaluated using CCK-8 assays, while drug sensitivity prediction reliability was determined through wound-healing assays.
We have successfully identified a set of nine genes, termed EFRGs, that hold significant potential for the establishment of a hepatocellular carcinoma-specific prognostic model. Furthermore, leveraging the individual risk scores derived from this model, we were able to stratify patients into two distinct risk groups, unveiling notable disparities in terms of immune infiltration patterns and response to immunotherapy. Notably, the model's capacity to accurately predict drug responses was substantiated through comprehensive experimental investigations, encompassing wound-healing assay, and CCK8 experiments conducted on the HepG2 and Huh7 cell lines.
We constructed an EFRGs model that serves as valuable tools for prognostic assessment and decision-making support in the context of immunotherapy and chemotherapy.
肝细胞癌 (HCC) 是一种突出的胃肠道恶性肿瘤，临床预后较差。在这方面，发现新的早期生物标志物有很大希望改善与 HCC 相关的死亡率。噬作用是一种重要的免疫过程，在清除凋亡细胞中起着核心作用。然而，全面研究噬作用相关基因 (EFRGs) 在 HCC 中的作用的研究很少，它们对 HCC 免疫治疗和靶向药物干预的调节影响知之甚少。
从 TCGA 数据库中获取 HCC 患者的 RNA 测序数据和临床特征。为了鉴定 HCC 中具有预后意义的基因，我们使用 limma 包进行了单变量 Cox 回归分析。随后，使用机器学习算法识别了枢纽基因。为了评估不同 HCC 亚型的免疫景观，我们使用了 CIBERSORT 算法。此外，使用单细胞 RNA 测序 (scRNA-seq) 来研究免疫细胞中 EFRGs 的表达水平，并探索 HCC 组织内的细胞间通讯。使用 CCK-8 测定评估 HCC 细胞的迁移能力，通过划痕愈合测定确定药物敏感性预测的可靠性。
我们成功鉴定了一组 9 个基因，称为 EFRGs，它们具有建立 HCC 特异性预后模型的巨大潜力。此外，利用该模型得出的个体风险评分，我们能够将患者分为两个不同的风险组，揭示了在免疫浸润模式和对免疫治疗的反应方面的显著差异。值得注意的是，该模型通过对 HepG2 和 Huh7 细胞系进行的划痕愈合测定和 CCK8 实验等全面的实验研究，准确预测药物反应的能力得到了证实。
我们构建了一个 EFRGs 模型，该模型可作为免疫治疗和化疗背景下预后评估和决策支持的有价值的工具。
