Integrating transcriptome and metabolomics analyses of hepatocellular carcinoma to discover novel biomarkers and drug targets

IF 2.6 4区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Clinics and research in hepatology and gastroenterology Pub Date : 2025-02-10 DOI:10.1016/j.clinre.2025.102546

Ting Yang, Si-Yu Wang

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引用次数: 0

Abstract

Background

Hepatocellular carcinoma (HCC) ranks sixth in incidence and third in mortality among all cancers. Chronic infection by hepatitis B and C viruses are the predominant risk factors for HCC, but other factors related to metabolic disorders including diabetes and obesity are also involved.

Methods

Ten male HCC patients with chronic HBV infection were included in this study. Primary HCC tissues were obtained from all study participants following liver resection. Normal tissues that were simultaneously collected served as the controls and were defined as tissue at least 5 cm from the tumor edge. Tissues were subjected to untargeted metabolomics and transcriptome analyses.

Results

We identified 31 and 41 differentially expressed metabolites (DEMs) in positive and negative ion modes, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that 15 DEMs were enriched in ABC transporters, nine in purine metabolism, eight in central carbon metabolism in cancer, and seven in biosynthesis of amino acids. Regarding the transcriptome analysis, 1,224 significantly up-regulated and 887 down-regulated RNAs were found. KEGG pathway analysis revealed that the most significantly enriched pathways were metabolic pathways. Integrated analysis showed seven pathways that were highly activated in HCC tissues including PI3K/Akt, ABC transporters, caffeine metabolism, carbon metabolism, biosynthesis of amino acids, arginine biosynthesis, alanine, aspartate, and glutamate metabolism.

Conclusion

Some DEMs could be biomarkers or therapeutic targets for HCC. Moreover, we found that MAGEB2 was significantly elevated in HCC tissues for the first time, and its association with HCC needs to be explored by functional studies.

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整合肝细胞癌的转录组学和代谢组学分析，发现新的生物标志物和药物靶点

背景：在所有癌症中，肝细胞癌（HCC）的发病率排名第六，死亡率排名第三。乙型和丙型肝炎病毒的慢性感染是HCC的主要危险因素，但与糖尿病和肥胖等代谢紊乱相关的其他因素也参与其中。方法选择10例男性HCC合并慢性HBV感染患者为研究对象。所有研究参与者在肝切除术后获得原发性HCC组织。同时采集的正常组织作为对照，定义为离肿瘤边缘至少5厘米的组织。组织进行非靶向代谢组学和转录组学分析。结果在正离子和负离子模式下分别鉴定出31种和41种差异表达代谢物（DEMs）。京都基因与基因组百科全书（KEGG）分析显示，15个dem富集于ABC转运蛋白，9个富集于嘌呤代谢，8个富集于癌症中心碳代谢，7个富集于氨基酸的生物合成。在转录组分析中，发现1224个rna显著上调，887个rna显著下调。KEGG通路分析显示，代谢通路富集程度最高。综合分析显示，HCC组织中有7条通路高度激活，包括PI3K/Akt、ABC转运蛋白、咖啡因代谢、碳代谢、氨基酸生物合成、精氨酸生物合成、丙氨酸、天冬氨酸和谷氨酸代谢。结论部分dem可作为HCC的生物标志物或治疗靶点。此外，我们首次发现MAGEB2在HCC组织中显著升高，其与HCC的关系有待功能研究探索。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinics and research in hepatology and gastroenterology GASTROENTEROLOGY & HEPATOLOGY-

CiteScore

4.30

自引率

3.70%

发文量

198

审稿时长

42 days

期刊介绍： Clinics and Research in Hepatology and Gastroenterology publishes high-quality original research papers in the field of hepatology and gastroenterology. The editors put the accent on rapid communication of new research and clinical developments and so called "hot topic" issues. Following a clear Editorial line, besides original articles and case reports, each issue features editorials, commentaries and reviews. The journal encourages research and discussion between all those involved in the specialty on an international level. All articles are peer reviewed by international experts, the articles in press are online and indexed in the international databases (Current Contents, Pubmed, Scopus, Science Direct). Clinics and Research in Hepatology and Gastroenterology is a subscription journal (with optional open access), which allows you to publish your research without any cost to you (unless you proactively chose the open access option). Your article will be available to all researchers around the globe whose institution has a subscription to the journal.