Catalase expression is an independent prognostic marker in liver hepatocellular carcinoma

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-01-05 DOI:10.1515/oncologie-2023-0472

Yu-Chia Chen, Hsin-Hung Chen, Po-Ming Chen

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引用次数: 0

Abstract

Abstract Objectives Liver hepatocellular carcinoma (LIHC) is the most common type of primary liver cancer and originates from hepatocytes, the main functional cells of the liver. It is a serious and aggressive cancer with a generally poor prognosis, especially when diagnosed at advanced stages. Reactive oxygen species (ROS) have been detected in LIHC and are involved in carcinogenesis and tumor progression. Here, a comprehensive analysis was performed to evaluate the effects of ROS-related genes on the prognosis of LIHC. Methods Using bioinformatical tools including Gene Expression Profiling Interactive Analysis (GEPIA2) and Q-omics, a comprehensive analysis was performed to evaluate the effects of ROS-related genes, including superoxide dismutases (SODs), glutathione peroxidases (GPXs), peroxiredoxins (PRDXs) and catalase (CAT) on the prognosis of LIHC using The Cancer Genome Atlas (TCGA) dataset and identified the most appropriate candidate genes. Then we further explored their effects on LIHC cell proliferation and drug selection for LIHC treatment. Results We found that CAT expression was significantly downregulated in late stage’s LIHC tissues compared to normal liver or early stage’s LIHC tissues, and high CAT expression was correlated with a favorable survival prognosis in LIHC. The expression of the CAT gene was associated with an inhibition of the “cell cycle” pathway. HepG2 and Hep3B cells’ growth was increased with a decrease in CAT expression by silencing its mRNA. As silencing of CAT in HepG2 and Hep3B cells, and its association with an increase in the expression of PLK1, CCNB1, CDC20, and PTTG1. A comparative 426 drug response in LIHC cells with different CAT expression, SU11274, a Met inhibitor, could serve as a therapeutic option when CAT levels are low in LIHC cells. Conclusions Our findings revealed that Met inhibitors could potentially control tumor progression and be used as a therapeutic option against LIHC with low CAT.

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过氧化氢酶的表达是肝脏肝细胞癌的独立预后指标

摘要目的肝肝细胞癌（LIHC）是原发性肝癌中最常见的一种，起源于肝脏的主要功能细胞--肝细胞。它是一种严重的侵袭性癌症，预后普遍较差，尤其是在晚期确诊时。在 LIHC 中检测到了活性氧（ROS），它参与了癌变和肿瘤进展。在此，我们进行了一项综合分析，以评估 ROS 相关基因对 LIHC 预后的影响。方法利用基因表达谱交互分析（GEPIA2）和Q-omics等生物信息学工具，通过癌症基因组图谱（TCGA）数据集，对ROS相关基因（包括超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GPX）、过氧化还原酶（PRDX）和过氧化氢酶（CAT））对LIHC预后的影响进行了全面分析，并确定了最合适的候选基因。然后，我们进一步探讨了它们对 LIHC 细胞增殖和治疗 LIHC 药物选择的影响。结果我们发现，与正常肝脏或早期LIHC组织相比，CAT在晚期LIHC组织中的表达明显下调，CAT的高表达与LIHC的良好生存预后相关。CAT 基因的表达与 "细胞周期 "途径的抑制有关。通过沉默 CAT 的 mRNA，HepG2 和 Hep3B 细胞的生长随着 CAT 表达的减少而增加。由于 HepG2 和 Hep3B 细胞中 CAT 的沉默及其与 PLK1、CCNB1、CDC20 和 PTTG1 表达的增加有关。通过比较不同 CAT 表达的 LIHC 细胞对 426 药物的反应，当 LIHC 细胞中 CAT 水平较低时，Met 抑制剂 SU11274 可作为一种治疗选择。结论我们的研究结果表明，Met 抑制剂有可能控制肿瘤进展，并可作为一种治疗 CAT 低的 LIHC 的选择。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.