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作为与免疫浸润和铁死亡相关的肝细胞癌潜在预后生物标志物。

as a potential prognostic biomarker in hepatocellular carcinoma linked to immune infiltration and ferroptosis.

作者信息

Chen Hongyu, Ao Qiangguo, Wang Yueling, Qian Yue, Cheng Qingli, Zhang Wei

机构信息

Department of Nephrology, the Second Medical Center of PLA General Hospital, National Clinical Research Center for Geriatric Diseases, Beijing 100853, China.

Clinical Laboratory, the First Affiliated Hospital of Henan University, Kaifeng 475000, China.

出版信息

Chin J Cancer Res. 2024 Aug 30;36(4):378-397. doi: 10.21147/j.issn.1000-9604.2024.04.03.

DOI:10.21147/j.issn.1000-9604.2024.04.03
PMID:39246708
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11377886/
Abstract

OBJECTIVE

is expressed in numerous malignancies, including hepatocellular carcinomas (HCC), but its oncogenic function has not been elucidated. Here, we performed a comprehensive bioinformatics analysis of the Liver Hepatocellular Carcinoma (LIHC) dataset to investigate the function of in tumorgenesis.

METHODS

expression data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were validated by immunohistochemistry (IHC). Co-expression, differential expression, and functional analyses utilized TCGA-LIHC, Timer 2.0, Metascape, GTEx, and LinkedOmics databases. Associations with immune infiltration, ferroptosis, and immune checkpoint genes were assessed. Genetic changes were explored via CBioPortal. Logistic regression, receiver operating characteristic curve (ROC), Kaplan-Meier analysis, and nomogram modeling evaluated associations with HCC clinicopathological features. 's impact on proliferation and migration was studied in HepG2 and HuH7 cell lines.

RESULTS

was significantly elevated in HCC tumors compared to controls. -associated genes exhibited differential expression in pathways involving extracellular membrane ion channels. Significant associations were found between levels, immune infiltration, ferroptosis, and immune checkpoint genes in HCC tissue. levels correlated with HCC stage, histologic grade, and tumor status, and independently predicted overall and disease-specific survival. expression effectively distinguished between tumor and normal liver tissue. Spearman correlations highlighted a significant relationship between and ferroptosis-associated genes. Decreased levels in HepG2 and HuH7 cells resulted in reduced proliferation and migration.

CONCLUSIONS

was found to represent a promising biomarker within HCC diagnosis and prognosis together with being a possible drug-target.

摘要

目的

在包括肝细胞癌(HCC)在内的多种恶性肿瘤中均有表达,但其致癌功能尚未阐明。在此,我们对肝细胞癌(LIHC)数据集进行了全面的生物信息学分析,以研究其在肿瘤发生中的作用。

方法

通过免疫组织化学(IHC)验证了来自癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)的表达数据。利用TCGA-LIHC、Timer 2.0、Metascape、GTEx和LinkedOmics数据库进行共表达、差异表达和功能分析。评估了与免疫浸润、铁死亡和免疫检查点基因的关联。通过CBioPortal探索基因变化。逻辑回归、受试者工作特征曲线(ROC)、Kaplan-Meier分析和列线图建模评估了与HCC临床病理特征的关联。在HepG2和HuH7细胞系中研究了其对增殖和迁移的影响。

结果

与对照组相比,HCC肿瘤中显著升高。相关基因在涉及细胞外膜离子通道的途径中表现出差异表达。在HCC组织中,水平与免疫浸润、铁死亡和免疫检查点基因之间存在显著关联。水平与HCC分期、组织学分级和肿瘤状态相关,并独立预测总生存期和疾病特异性生存期。表达有效地鉴别了肿瘤和正常肝组织。Spearman相关性突出了与铁死亡相关基因之间的显著关系。HepG2和HuH7细胞中水平降低导致增殖和迁移减少。

结论

被发现是HCC诊断和预后中一个有前景的生物标志物,同时也是一个可能的药物靶点。