Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, China.
Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, China.
Aging (Albany NY). 2023 Jun 22;15(12):5751-5774. doi: 10.18632/aging.204830.
Hepatocellular carcinoma (HCC) is a heterogeneous malignancy with a rising prevalence worldwide. Immunotherapy has been shown to improve treatment outcomes for HCC. We aimed to construct a T-cell exhaustion-related gene prognostic model (TEXPM) for HCC and to elucidate the immunologic characteristics and advantages of immunotherapy in T-cell exhaustion-Related Gene-defined HCC groups.
Single-cell RNA sequencing data were used in conjunction with TCGA Differentially expressed genes (DEGs) to screen for T-cell exhaustion-Related Genes (TEXGs) for subsequent evaluation. Using univariate Cox regression analysis and LASSO regression analysis, five genes (FTL, GZMA, CD14, NPC2, and IER3) were subsequently selected for the construction of a TEXPM. Then, we evaluated the immunologic characteristics and advantages of immunotherapy in groups identified by TEXPM.
The TEXPM was formed with FTL, GZMA, CD14, NPC2, and IER3. The results of the training and validation team studies were consistent, with the low TEXPM group surviving longer than the high TEXPM group (P < 0.001). Multivariate Cox regression analysis demonstrated that TEXPM (HR: 2.347, 95%CI: 1.844-2.987; HR: 2.172, 95% CI: 1.689-2.793) was an independent prognostic variable for HCC patients. The low-TEXPM group was linked to active immunity, less aggressive phenotypes, strong infiltration of CD8+ T cells, CD4 + T cells, and M1 macrophages, and a better response to ICI treatment. A high TEXPM group, on the other hand, was associated with suppressive immunity, more aggressive phenotypes, a significant infiltration of B cells, M0 macrophages, and M2 macrophages, and a reduced response to ICI treatment. FTL is an independent prognostic variable in HCC patients and the knockdown of FTL can affect the biological behavior of hepatocellular carcinoma cells.
TEXPM is a promising prognostic biomarker connected to the immune system. Differentiating immunological and molecular features and predicting patient outcomes may be facilitated by TEXPM grouping. Furthermore, the expression of FTL was found to be an independent prognostic factor for HCC. Knockdown of FTL significantly inhibited proliferation, migration, and invasive activity in liver cancer cells.
肝细胞癌（HCC）是一种异质性恶性肿瘤，全球发病率呈上升趋势。免疫疗法已被证明可以改善 HCC 的治疗效果。我们旨在构建一个与 T 细胞耗竭相关的基因预后模型（TEXPM），并阐明免疫疗法在 T 细胞耗竭相关基因定义的 HCC 组中的免疫特征和优势。
使用单细胞 RNA 测序数据结合 TCGA 差异表达基因（DEGs）筛选与 T 细胞耗竭相关的基因（TEXGs），随后进行评估。采用单因素 Cox 回归分析和 LASSO 回归分析，选择五个基因（FTL、GZMA、CD14、NPC2 和 IER3）构建 TEXPM。然后，我们评估了 TEXPM 鉴定的组中免疫疗法的免疫特征和优势。
TEXPM 由 FTL、GZMA、CD14、NPC2 和 IER3 组成。训练组和验证组的结果一致，低 TEXPM 组的生存期长于高 TEXPM 组（P<0.001）。多因素 Cox 回归分析表明，TEXPM（HR：2.347，95%CI：1.844-2.987；HR：2.172，95%CI：1.689-2.793）是 HCC 患者的独立预后变量。低 TEXPM 组与主动免疫、侵袭性表型较弱、CD8+T 细胞、CD4+T 细胞和 M1 巨噬细胞浸润较强以及对 ICI 治疗反应较好有关。另一方面，高 TEXPM 组与抑制性免疫、侵袭性表型较强、B 细胞、M0 巨噬细胞和 M2 巨噬细胞浸润显著以及对 ICI 治疗反应降低有关。FTL 是 HCC 患者的独立预后变量，FTL 的敲低可以影响肝癌细胞的生物学行为。
TEXPM 是一种有前途的与免疫系统相关的预后生物标志物。通过 TEXPM 分组，可以区分免疫和分子特征并预测患者预后。此外，FTL 的表达被发现是 HCC 的独立预后因素。FTL 的敲低显著抑制肝癌细胞的增殖、迁移和侵袭活性。
