Development and experimental validation of a machine learning-based disulfidptosis-related ferroptosis score for hepatocellular carcinoma
Development and experimental validation of a machine learning-based disulfidptosis-related ferroptosis score for hepatocellular carcinoma
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DOI：
10.1007/s10495-023-01900-x
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发表时间：
2023-10
期刊：
影响因子：
7.2
通讯作者：
Cong Zhang;Tiantian Xu;Kun Ji;Shoujin Cao;Jing Ai;Junhan Pan;Yunbo Cao;Yuning Yang;
中科院分区：
文献类型：
--
作者：
Cong Zhang;Tiantian Xu;Kun Ji;Shoujin Cao;Jing Ai;Junhan Pan;Yunbo Cao;Yuning Yang;
二硫下垂和铁性下垂是两种不同的程序性细胞死亡途径，由于其潜在的治疗靶点而引起了人们的极大关注。然而，尽管这些途径具有重要意义，但与二硫下垂相关的铁下垂基因在肝细胞癌中的作用仍不清楚。在这项研究中，我们采用了一种综合的方法，利用各种复杂的技术，如皮尔逊分析、差异分析、单因素COX回归、套索分析、RANGER和多变量COX回归来计算二硫化下垂相关的下垂(DRF)评分。然后，我们将肝癌患者分为高分组和低分组，以检查DRF评分与各种预后的相关性，包括预后、功能丰富、免疫浸润、免疫治疗、TACE敏感性、药物敏感性和单细胞水平功能。最后，我们进行了体外实验，以验证KIF20A的功能。我们的分析表明，KIF20A、G6PD、SLC7A11和SLC2A1是构成DRF评分的完整基因。我们的研究结果显示，与DRF评分高的患者相比，DRF评分低的患者预后明显更好，对免疫治疗、TACE和化疗的反应也更好。基于我们从整体RNA-SEQ、单细胞RNA-SEQ和体外实验中获得的结果，我们确定细胞周期途径是高得分组和低得分组之间的主要区分因素。本研究揭示了与二硫下垂相关的铁下垂基因在肝细胞癌发生发展中的作用。从这项研究中收集到的信息可以帮助我们更好地理解它们作为肝癌治疗靶点的潜力。
Disulfidoptosis and ferroptosis are two distinct programmed cell death pathways that have garnered considerable attention due to their potential as therapeutic targets. However, despite their significance of these pathways, the role of disulfidoptosis-related ferroptosis genes in hepatocellular carcinoma (HCC) remains unclear. In this study, we employed a comprehensive approach that utilized various sophisticated techniques such as Pearson analysis, differential analysis, uniCox regression, lasso, ranger, and multivariable Cox regression to develop the disulfidoptosis-related ferroptosis (DRF) score. We then classified patients with HCC into high- and low-score groups to examine the association between the DRF score and various outcomes, including prognosis, functional enrichment, immune infiltration, immunotherapy, TACE sensitivity, drug sensitivity, and single-cell level function. Finally, we conducted in vitro experiments to validate the function of KIF20A. Our analysis revealed that KIF20A, G6PD, SLC7A11, and SLC2A1 were integral to constructing the DRF score. Our findings showed that patients with low DRF scores had significantly better prognoses and were more responsive to immunotherapy, TACE, and chemotherapy than those with high DRF scores. Based on our results obtained from bulk RNA-seq, single-cell RNA-seq, and in vitro experiments, we identified the cell cycle pathway as the primary distinguished factor between high-score and low-score groups. This study sheds light on the contribution of disulfidoptosis-related ferroptosis genes to the development and progression of HCC. The information gleaned from this study can be leveraged to improve our understanding of their potential as therapeutic targets for HCC treatment.