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肝细胞癌中对氧磷酶1表达的转录组学分析及其对肿瘤免疫的潜在影响。

Transcriptomic analysis of Paraoxonase 1 expression in hepatocellular carcinoma and its potential impact on tumor immunity.

作者信息

Dong Linhuan, Dong Changjun, Yu Yunlin, Jiao Xin, Zhang Xiangwei, Zhang Xianlin, Li Zheng

机构信息

Department of General surgery, Affiliated Renhe Hospital of China Three Gorges University, Yichang, 443000, China.

Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, 443002, China.

出版信息

Clin Transl Oncol. 2025 Feb;27(2):612-629. doi: 10.1007/s12094-024-03598-y. Epub 2024 Jul 20.

Abstract

BACKGROUND

Hepatocellular carcinoma (HCC) is characterized by a complex pathogenesis that confers aggressive malignancy, leading to a lack of dependable biomarkers for predicting invasion and metastasis, which results in poor prognoses in patients with HCC. Glycogen storage disease (GSD) is an uncommon metabolic disorder marked by hepatomegaly and liver fibrosis. Notably, hepatic adenomas in GSD patients present a heightened risk of malignancy compared to those in individuals without the disorder. In this investigation, PON1 emerged as a potential pivotal gene for HCC through bioinformatics analysis.

METHODS

Transcriptomic profiling data of liver cancer were collected and integrated from TCGA and GEO databases. Bioinformatics analysis was conducted to identify mutated mRNAs associated with GSD, and the PON1 gene was selected as a key gene. Patients were grouped based on the expression levels of PON1, and differences in clinical characteristics, biological pathways, immune infiltration, and expression of immune checkpoints were compared.

RESULTS

The expression levels of the PON1 gene showed significant differences between the high-expression group and the low-expression group in HCC patients. Further analysis indicated that the PON1 gene at different expression levels might influence the clinical manifestations, biological processes, immune infiltration, and expression of immune checkpoints in HCC. Additionally, immunohistochemistry (IHC) results revealed high expression of PON1 in normal tissues and low expression in HCC tissues. These findings provide important clues and future research directions for the early diagnosis, prognosis, immunotherapy, and potential molecular interactions of HCC.

CONCLUSION

Our investigation underscores the noteworthy prognostic significance of PON1 in HCC, suggesting its potential pivotal role in modulating tumor progression and immune cell infiltration. These findings establish PON1 as a novel tumor biomarker with significant implications for the prognosis, targeted therapy, and immunotherapy of patients with HCC.

摘要

背景

肝细胞癌(HCC)的发病机制复杂,具有侵袭性恶性特征,导致缺乏可靠的预测侵袭和转移的生物标志物,从而使HCC患者预后较差。糖原贮积病(GSD)是一种罕见的代谢紊乱疾病,其特征为肝肿大和肝纤维化。值得注意的是,与非GSD患者相比,GSD患者的肝腺瘤发生恶性肿瘤的风险更高。在本研究中,通过生物信息学分析,对氧磷酶1(PON1)成为HCC的一个潜在关键基因。

方法

从TCGA和GEO数据库收集并整合肝癌的转录组分析数据。进行生物信息学分析以鉴定与GSD相关的突变mRNA,并选择PON1基因作为关键基因。根据PON1的表达水平对患者进行分组,并比较临床特征、生物学途径、免疫浸润和免疫检查点表达的差异。

结果

HCC患者中,PON1基因的表达水平在高表达组和低表达组之间存在显著差异。进一步分析表明,不同表达水平的PON1基因可能影响HCC的临床表现、生物学过程、免疫浸润和免疫检查点的表达。此外,免疫组织化学(IHC)结果显示,PON1在正常组织中高表达,而在HCC组织中低表达。这些发现为HCC的早期诊断、预后、免疫治疗以及潜在的分子相互作用提供了重要线索和未来研究方向。

结论

我们的研究强调了PON1在HCC中具有显著的预后意义,表明其在调节肿瘤进展和免疫细胞浸润方面可能具有关键作用。这些发现确立了PON1作为一种新型肿瘤生物标志物,对HCC患者的预后、靶向治疗和免疫治疗具有重要意义。

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