Sun Jianming, Liu Chun, Liu Dongdong, Hu Xinlian, Ren Shirong, Jiang Guoying, Zhang Daizhong, Hu Shuai, Yuan Xiaojing, Tao Jun
Department of General Surgery, Dazhou Central Hospital, Dazhou, 635000, China.
Department of Oncology, Chongqing General Hospital, Chongqing University, Chongqing, 401147, China.
Discov Oncol. 2025 Aug 17;16(1):1569. doi: 10.1007/s12672-025-03362-w.
OBJECTIVES: This study aimed to delineate global research trends in immunogenic cell death (ICD) within hepatocellular carcinoma (HCC) by mapping collaborative networks, thematic shifts, and high-impact findings. Using VOSviewer network visualisation and R-bibliometrix quantitative metrics, we sought to show how scientific output has evolved and to pinpoint research gaps that may guide future investigations. METHODS: We retrieved 568 publications from the Web of Science Core Collection (2000-2024) using a tailored keyword strategy encompassing "Hepatocellular carcinoma" and "Immunogenic cell death." Data were analyzed with VOSviewer and R-bibliometrix to visualize co-authorship patterns, keyword clusters, institutional collaborations, and citation metrics. RESULTS: Annual publication volumes rose markedly, peaking at 68 in 2023, and this quantitative surge parallels a qualitative shift toward clinically actionable research outputs. Over the entire period, the corpus accumulated 13 161 citations (mean 23.2 citations/article), indicating strong and growing academic influence. Keyword co-occurrence revealed three main clusters highlighting immunotherapeutic mechanisms, molecular pathways (e.g., HMGB1 and calreticulin), and epidemiological concerns. China and the United States led in overall output, with universities such as the University of California System, Harvard University, and Shanghai-based institutions forming robust collaborative networks. Highly cited articles, such as Zhong et al. (2016, Cell) on autophagy-inflammation crosstalk and Yu et al. (2020, ACS Nano) on mitophagy-augmented doxorubicin, underscored the role of autophagy, checkpoint inhibitors, and combination therapies in harnessing ICD to overcome HCC's immunosuppressive microenvironment. These patterns indicate that the field is transitioning from descriptive bibliometrics to translational studies, signalling that forthcoming work will likely accelerate rational design of ICD-based clinical trials and inform funding priorities. CONCLUSION: The findings confirm ICD as an emerging cornerstone of HCC research, with demonstrated capacity to reshape clinical-trial portfolios and refine biomarker-driven patient stratification, reflecting both deeper mechanistic insights and accelerating translational efforts. Ongoing challenges include refining biomarkers, integrating ICD inducers with immunotherapies, and accounting for HCC's inherent complexities such as chronic liver disease and metabolic dysfunction. Future research directions focus on the use of nanotechnology for precise drug delivery, the integration of metabolomics and genomics data to enable personalised treatment, and the improvement of combination therapies combined with local interventions.
目的:本研究旨在通过绘制合作网络、主题转变和高影响力研究成果,描绘肝细胞癌(HCC)中免疫原性细胞死亡(ICD)的全球研究趋势。我们使用VOSviewer网络可视化和R-bibliometrix定量指标,试图展示科学产出是如何演变的,并找出可能指导未来研究的差距。 方法:我们使用包含“肝细胞癌”和“免疫原性细胞死亡”的定制关键词策略,从科学网核心合集(2000 - 2024年)中检索了568篇出版物。使用VOSviewer和R-bibliometrix对数据进行分析,以可视化共同作者模式、关键词聚类、机构合作和引用指标。 结果:年度出版物数量显著增加,在2023年达到68篇的峰值,这种数量上的激增与向临床可操作研究成果的质量转变相平行。在整个时期,该文献库累计获得13161次引用(平均每篇文章23.2次引用),表明其学术影响力强大且不断增长。关键词共现揭示了三个主要聚类,突出了免疫治疗机制、分子途径(如高迁移率族蛋白B1和钙网蛋白)以及流行病学关注点。中国和美国在总体产出方面领先,加利福尼亚大学系统、哈佛大学等大学以及上海的机构形成了强大的合作网络。高被引文章,如Zhong等人(2016年,《细胞》)关于自噬 - 炎症相互作用以及Yu等人(2020年,《美国化学会纳米》)关于线粒体自噬增强阿霉素的文章,强调了自噬、检查点抑制剂和联合疗法在利用ICD克服HCC免疫抑制微环境中的作用。这些模式表明该领域正在从描述性文献计量学向转化研究转变,这意味着即将开展的工作可能会加速基于ICD的临床试验的合理设计,并为资金优先事项提供参考。 结论:研究结果证实ICD是HCC研究的一个新兴基石,具有重塑临床试验组合和完善生物标志物驱动的患者分层的能力,反映了更深入的机制见解和加速的转化努力。当前的挑战包括完善生物标志物、将ICD诱导剂与免疫疗法整合,以及考虑HCC固有的复杂性,如慢性肝病和代谢功能障碍。未来的研究方向集中在利用纳米技术进行精确药物递送、整合代谢组学和基因组学数据以实现个性化治疗,以及改进联合疗法与局部干预相结合。
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