TACE responser NDRG1 acts as a guardian against ferroptosis to drive tumorgenesis and metastasis in HCC.

IF 3.7 3区生物学 Q1 BIOCHEMICAL RESEARCH METHODS Biological Procedures Online Pub Date : 2023-05-19 DOI:10.1186/s12575-023-00199-x

Bufu Tang, Yajie Wang, Jinyu Zhu, Jingjing Song, Shiji Fang, Qiaoyou Weng, Yang Yang, Jianfei Tu, Zhongwei Zhao, Minjiang Chen, Min Xu, Weiqian Chen, Jiansong Ji

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引用次数: 1

Abstract

Background: The treatment efficacy of transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) varies widely between individuals. The aim of this study was to identify subtype landscapes and responser related to TACE, and further clarify the regulatory effect and corresponding mechanism of NDRG1 on HCC tumorgenesis and metastasis.

Methods: The principal component analysis (PCA) algorithm was used to construct a TACE response scoring (TRscore) system. The random forest algorithm was applied to identify the TACE response-related core gene NDRG1 of HCC, and its role in the prognosis of HCC was explored. The role of NDRG1 in the progression and metastasis of HCC and functional mechanism were confirmed using several experimental methods.

Results: Based on the GSE14520 and GSE104580 cohorts, we identified 2 TACE response-related molecular subtypes for HCC with significant differences in clinical features, and the TACE prognosis of Cluster A was significantly better than that of Cluster B (p < 0.0001). We then established the TRscore system and found that the low TRscore group showed a higher probability of survival and a lower rate of recurrence than the high TRscore group (p < 0.05) in both the HCC and TACE-treated HCC cohorts within the GSE14520 cohort. NDRG1 was determined to be the the hub gene associated with the TACE response of HCC and its high expression suggested a poor prognosis. Furthermore, The suppression of NDRG1 konckdown in tumorgenesis and metastasis of HCC was clarified in both vivo and vitro, which was importantly achieved through inducing ferroptosis in HCC cells, especially contributing to RLS3-induced ferroptosis.

Conclusion: The constructed TACE response-related molecular subtypes and TRscores can specifically and accurately predict TACE prognosis for HCC. In addition, the TACE response-related hub gene NDRG1 may act as a guardian against ferroptosis to drive tumorgenesis and metastasis in HCC, which laid a new foundation for the development of new potential targeted therapy strategies to improve disease prognosis in HCC patients.

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在HCC中，TACE应答者NDRG1作为铁下垂的守护者，驱动肿瘤发生和转移。

背景:经动脉化疗栓塞(TACE)治疗肝细胞癌(HCC)的疗效在个体之间差异很大。本研究旨在鉴定与TACE相关的亚型格局及应答物，进一步阐明NDRG1对HCC肿瘤发生转移的调控作用及相应机制。方法:采用主成分分析(PCA)算法构建TACE反应评分(TRscore)系统。应用随机森林算法识别HCC TACE反应相关核心基因NDRG1，探讨其在HCC预后中的作用。多种实验方法证实了NDRG1在HCC进展转移中的作用及其作用机制。结果:基于GSE14520和GSE104580队列，我们确定了2个临床特征有显著差异的HCC TACE反应相关分子亚型，A类TACE预后明显好于B类(p)。结论:构建的TACE反应相关分子亚型和trscore能够特异性、准确预测HCC TACE预后。此外，TACE应答相关枢纽基因NDRG1可能作为铁上沉的守护者，驱动HCC的肿瘤发生和转移，这为开发新的潜在靶向治疗策略，改善HCC患者的疾病预后奠定了新的基础。

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

Biological Procedures Online 生物-生化研究方法

CiteScore

10.50

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0.00%

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审稿时长

>12 weeks

期刊介绍： iological Procedures Online publishes articles that improve access to techniques and methods in the medical and biological sciences. We are also interested in short but important research discoveries, such as new animal disease models. Topics of interest include, but are not limited to: Reports of new research techniques and applications of existing techniques Technical analyses of research techniques and published reports Validity analyses of research methods and approaches to judging the validity of research reports Application of common research methods Reviews of existing techniques Novel/important product information Biological Procedures Online places emphasis on multidisciplinary approaches that integrate methodologies from medicine, biology, chemistry, imaging, engineering, bioinformatics, computer science, and systems analysis.