Department of Thoracic Surgery, The People's Hospital of Beilun District, Ningbo, Zhejiang, China.
Health Science Center, Ningbo University, Zhejiang, China.
Medicine (Baltimore). 2023 Nov 17;102(46):e36190. doi: 10.1097/MD.0000000000036190.
Liver hepatocellular carcinoma (LIHC) is characterized by high morbidity, rapid progression and early metastasis. Although many efforts have been made to improve the prognosis of LIHC, the situation is still dismal. Inability to initiate anoikis process is closely associated with cancer proliferation and metastasis, affecting patients' prognosis. In this study, a corresponding gene signature was constructed to comprehensively assess the prognostic value of anoikis-related genes (ARGs) in LIHC. Using TCGA-LIHC dataset, the mRNA levels of the differentially expressed ARGs in LIHC and normal tissues were compared by Student t test. And prognostic ARGs were identified through Cox regression analysis. Prognostic signature was established and then externally verified by ICGC-LIRI-JP dataset and GES14520 dataset via LASSO Cox regression model. Potential functions and mechanisms of ARGs in LIHC were evaluated by functional enrichment analyses. And the immune infiltration status in prognostic signature was analyzed by ESTIMATE algorithm and ssGSEA algorithm. Furthermore, ARGs expression in LIHC tissues was validated via qRT-PCR and IHC staining from the HPA website. A total of 97 differentially expressed ARGs were detected in LIHC tissues. Functional enrichment analysis revealed these genes were mainly involved in MAP kinase activity, apoptotic signaling pathway, anoikis and PI3K-Akt signaling pathway. Afterward, the prognostic signature consisting of BSG, ETV4, EZH2, NQO1, PLK1, PBK, and SPP1 had a moderate to high predictive accuracy and served as an independent prognostic indicator for LIHC. The prognostic signature was also applicable to patients with distinct clinical parameters in subgroup survival analysis. And it could reflect the specific immune microenvironment in LIHC, which indicated high-risk group tended to profit from ICI treatment. Moreover, qRT-PCR and IHC staining showed increasing expression of BSG, ETV4, EZH2, NQO1, PLK1, PBK and SPP1in LIHC tissues, which were consistent to the results from TCGA database. The current study developed a novel prognostic signature comprising of 7 ARGs, which could stratify the risk and effectively predict the prognosis of LIHC patients. Furthermore, it also offered a potential indicator for immunotherapy of LIHC.
肝细胞癌（LIHC）的特点是发病率高、进展迅速、早期转移。尽管为改善 LIHC 的预后做出了许多努力，但情况仍然不容乐观。无法启动失巢凋亡过程与癌症增殖和转移密切相关，影响患者的预后。在这项研究中，构建了一个相应的基因特征，以全面评估失巢凋亡相关基因（ARGs）在 LIHC 中的预后价值。使用 TCGA-LIHC 数据集，通过 Student t 检验比较 LIHC 和正常组织中差异表达的 ARGs 的 mRNA 水平。并通过 Cox 回归分析确定预后 ARGs。通过 LASSO Cox 回归模型，利用 ICGC-LIRI-JP 数据集和 GES14520 数据集建立并外部验证预后特征。通过功能富集分析评估 ARGs 在 LIHC 中的潜在功能和机制。并通过 ESTIMATE 算法和 ssGSEA 算法分析预后特征中的免疫浸润状态。此外，通过 HPA 网站的 qRT-PCR 和 IHC 染色验证 LIHC 组织中 ARGs 的表达。在 LIHC 组织中检测到 97 个差异表达的 ARGs。功能富集分析显示这些基因主要参与 MAP 激酶活性、凋亡信号通路、失巢凋亡和 PI3K-Akt 信号通路。随后，由 BSG、ETV4、EZH2、NQO1、PLK1、PBK 和 SPP1 组成的预后特征具有中等到高度的预测准确性，并作为 LIHC 的独立预后指标。在亚组生存分析中，预后特征也适用于具有不同临床参数的患者。并且它可以反映 LIHC 特定的免疫微环境，这表明高危组可能从 ICI 治疗中获益。此外，qRT-PCR 和 IHC 染色显示 BSG、ETV4、EZH2、NQO1、PLK1、PBK 和 SPP1 在 LIHC 组织中的表达增加，与 TCGA 数据库的结果一致。本研究构建了一个由 7 个 ARGs 组成的新型预后特征，可对风险进行分层，有效预测 LIHC 患者的预后。此外，它还为 LIHC 的免疫治疗提供了一个潜在的指标。
