Yang Liang, Li Peiping, Zhao JiaLi, Bai Zirui, Zeng Guifang, Liu Xialei, Zou Baojia, Li Jian
Department of Hepatobiliary Surgery, The Fifth Affiliated Hospital of Sun Yat-Sen University, 52 Mei Hua East Road, Zhuhai, 519000, Guangdong Province, China.
Discov Oncol. 2025 Mar 7;16(1):272. doi: 10.1007/s12672-025-02051-y.
Hepatocellular carcinoma (HCC) is a malignant tumour characterized by high morbidity and mortality. Immunotherapy is an important treatment newly approved for the treatment for advanced hepatocellular carcinoma. However, how NASH progresses to HCC and the association between the immune signature in HCC and patient prognosis remain unclear.
Data from NASH and NASH-HCC patients were obtained from the GEO database. Differentially expressed genes were screened and hub genes were identified. The enrichment analysis, clustering, cibersort, ssGSEA, Xcell and immune checkpoint expression data of the samples were analysed. Survival analysis of dual genes was performed using TCGA liver cancer samples and the lasso regression model, and Cox regression analysis was conducted. Pathology specimens from 21 NASH-associated hepatocellular carcinoma patients were collected, and immunohistochemical staining was used to verify gene expression.
Compared with HCC patients with high CAT and low CXCL8 expression, those with low CAT and high CXCL8 expression had significantly higher levels of infiltration of multiple immune cell types and the common immune checkpoints CD274, PDCD1 and CTLA4. Furthermore, CAT was a protective factor, and CXCL8 was a risk factor for the prognosis of HCC patients.
CAT and CXCL8 might impact NASH-HCC progression. HCC patients with low CAT and high CXCL8 expression might have more extensive immune cell infiltration and stronger tumour immune escape. However, probably due to their different effects on CD8 + T cells and reactive oxygen species, increased expression of CAT contributes to improved prognosis in HCC patients, whereas increased expression of CXCL8 leads to a poor prognosis.
肝细胞癌（HCC）是一种发病率和死亡率都很高的恶性肿瘤。免疫疗法是新批准用于治疗晚期肝细胞癌的重要治疗方法。然而，非酒精性脂肪性肝炎（NASH）如何进展为HCC以及HCC中的免疫特征与患者预后之间的关联仍不清楚。
从基因表达综合数据库（GEO数据库）获取NASH和NASH-HCC患者的数据。筛选差异表达基因并鉴定核心基因。对样本的富集分析、聚类分析、Cibersort分析、单样本基因集富集分析（ssGSEA）、Xcell分析和免疫检查点表达数据进行分析。使用癌症基因组图谱（TCGA）肝癌样本和套索回归模型对双基因进行生存分析，并进行Cox回归分析。收集21例NASH相关肝细胞癌患者的病理标本，采用免疫组织化学染色验证基因表达。
与CAT高表达和CXCL8低表达的HCC患者相比，CAT低表达和CXCL8高表达的患者多种免疫细胞类型以及常见免疫检查点CD274、程序性死亡受体1（PDCD1）和细胞毒性T淋巴细胞相关蛋白4（CTLA4）的浸润水平显著更高。此外，CAT是HCC患者预后的保护因素，而CXCL8是危险因素。
CAT和CXCL8可能影响NASH-HCC的进展。CAT低表达和CXCL8高表达的HCC患者可能有更广泛的免疫细胞浸润和更强的肿瘤免疫逃逸。然而，可能由于它们对CD8 + T细胞和活性氧的影响不同，CAT表达增加有助于改善HCC患者的预后，而CXCL8表达增加则导致预后不良。
