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

作者：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 · 发表于：Biological Procedures Online · 年份：2023 · DOI：10.1186/s12575-023-00199-x · 被引用次数：18 · 研究领域：Mechanisms of cancer metastasis、Hippo pathway signaling and YAP/TAZ、Cancer Mechanisms and Therapy

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 metastas...