{"title":"免疫细胞与肝细胞癌之间的因果关系：孟德尔随机化（MR）","authors":"Pengkhun Nov, Yangfeng Zhang, Duanyu Wang, Syphanna Sou, Socheat Touch, Samnang Kouy, Virak Vicheth, Lilin Li, Xiang Liu, Changqian Wang, Peizan Ni, Qianzi Kou, Ying Li, Chongyang Zheng, Arzoo Prasai, Wen Fu, Wandan Li, Kunpeng Du, Jiqiang Li","doi":"10.3332/ecancer.2024.1794","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>Hepatocellular carcinoma (HCC) is a complex and multifaceted disease that is increasingly prevalent globally. The involvement of immune cells in the tumour microenvironment has been linked to the progression of HCC, but the exact cause-and-effect relationship is not yet clear. In this study, we utilise Mendelian randomization (MR) to investigate the potential causal links between immune factors and the development of HCC.</p><p><strong>Method: </strong>We executed a comprehensive MR study, leveraging publicly accessible genetic datasets to explore the potential causal links between 731 types of immune cells and HCC. Our analysis primarily applied inverse variance weighting and weighted median methods. To evaluate the robustness of our findings and probe for the presence of heterogeneity and pleiotropy, we also conducted thorough sensitivity analyses.</p><p><strong>Results: </strong>We found 36 immune cells were associated with HCC, CD64 on CD14- CD16+ monocytes (OR = 1.328, 95% CI = 1.116- 1.581, <i>p</i> = 0.001), CD3- lymphocyte %lymphocytes (OR = 1.341, 95% CI = 1.027- 1.750, p = 0.031), HLA DR on CD14+ monocytes (OR = 1.256, 95% CI = 1.089- 1.448, <i>p</i> = 0.002), CD19 on CD19 on Plasma Blast-Plasma Cell (OR = 1.224, 95% CI = 1.073- 1.396, <i>p</i> = 0.003), CCR2 on monocytes (OR = 1.204, 95% CI = 1.073- 1.351, <i>p</i> = 0.002) and Naive CD4+ T cell Absolute Count (OR = 0.797, 95% CI = 0.655- 0.969, <i>p</i> = 0.023) were the most strongly associated with HCC. Among them, CD64 on CD14- CD16+ monocytes, CD3 - lymphocyte %lymphocytes, HLA DR on CD14+ monocytes and CD19 on Plasma Blast-Plasma Cells are the risk factors, while Naive CD4+ T cell Absolute Count are protective factors for HCC.</p><p><strong>Conclusion: </strong>Our MR analysis of the role of immune cells and HCC provides a framework for knowledge of circulating immune status. Systematic assays of infiltrating immune cells in HCC can help dissect the immune status of HCC, assess the current use of checkpoint blockers, and most importantly, aid in the development of innovative immunotherapies. Further research is necessary to validate these findings and explore the underlying mechanisms that influence the immune response to HCC.</p>","PeriodicalId":11460,"journal":{"name":"ecancermedicalscience","volume":"18 ","pages":"1794"},"PeriodicalIF":1.2000,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11735144/pdf/","citationCount":"0","resultStr":"{\"title\":\"The causal relationship between immune cells and hepatocellular carcinoma: a Mendelian randomization (MR).\",\"authors\":\"Pengkhun Nov, Yangfeng Zhang, Duanyu Wang, Syphanna Sou, Socheat Touch, Samnang Kouy, Virak Vicheth, Lilin Li, Xiang Liu, Changqian Wang, Peizan Ni, Qianzi Kou, Ying Li, Chongyang Zheng, Arzoo Prasai, Wen Fu, Wandan Li, Kunpeng Du, Jiqiang Li\",\"doi\":\"10.3332/ecancer.2024.1794\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>Hepatocellular carcinoma (HCC) is a complex and multifaceted disease that is increasingly prevalent globally. The involvement of immune cells in the tumour microenvironment has been linked to the progression of HCC, but the exact cause-and-effect relationship is not yet clear. In this study, we utilise Mendelian randomization (MR) to investigate the potential causal links between immune factors and the development of HCC.</p><p><strong>Method: </strong>We executed a comprehensive MR study, leveraging publicly accessible genetic datasets to explore the potential causal links between 731 types of immune cells and HCC. Our analysis primarily applied inverse variance weighting and weighted median methods. To evaluate the robustness of our findings and probe for the presence of heterogeneity and pleiotropy, we also conducted thorough sensitivity analyses.</p><p><strong>Results: </strong>We found 36 immune cells were associated with HCC, CD64 on CD14- CD16+ monocytes (OR = 1.328, 95% CI = 1.116- 1.581, <i>p</i> = 0.001), CD3- lymphocyte %lymphocytes (OR = 1.341, 95% CI = 1.027- 1.750, p = 0.031), HLA DR on CD14+ monocytes (OR = 1.256, 95% CI = 1.089- 1.448, <i>p</i> = 0.002), CD19 on CD19 on Plasma Blast-Plasma Cell (OR = 1.224, 95% CI = 1.073- 1.396, <i>p</i> = 0.003), CCR2 on monocytes (OR = 1.204, 95% CI = 1.073- 1.351, <i>p</i> = 0.002) and Naive CD4+ T cell Absolute Count (OR = 0.797, 95% CI = 0.655- 0.969, <i>p</i> = 0.023) were the most strongly associated with HCC. Among them, CD64 on CD14- CD16+ monocytes, CD3 - lymphocyte %lymphocytes, HLA DR on CD14+ monocytes and CD19 on Plasma Blast-Plasma Cells are the risk factors, while Naive CD4+ T cell Absolute Count are protective factors for HCC.</p><p><strong>Conclusion: </strong>Our MR analysis of the role of immune cells and HCC provides a framework for knowledge of circulating immune status. Systematic assays of infiltrating immune cells in HCC can help dissect the immune status of HCC, assess the current use of checkpoint blockers, and most importantly, aid in the development of innovative immunotherapies. Further research is necessary to validate these findings and explore the underlying mechanisms that influence the immune response to HCC.</p>\",\"PeriodicalId\":11460,\"journal\":{\"name\":\"ecancermedicalscience\",\"volume\":\"18 \",\"pages\":\"1794\"},\"PeriodicalIF\":1.2000,\"publicationDate\":\"2024-11-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11735144/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ecancermedicalscience\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.3332/ecancer.2024.1794\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q4\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ecancermedicalscience","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3332/ecancer.2024.1794","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q4","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
目的：肝细胞癌（HCC）是一种复杂的、多方面的疾病，在全球范围内日益流行。免疫细胞在肿瘤微环境中的参与与HCC的进展有关，但确切的因果关系尚不清楚。在这项研究中，我们利用孟德尔随机化（MR）来研究免疫因素与HCC发展之间的潜在因果关系。方法：我们进行了一项全面的MR研究，利用可公开访问的遗传数据集来探索731种免疫细胞与HCC之间的潜在因果关系。我们的分析主要采用方差逆加权和加权中位数法。为了评估我们研究结果的稳健性，并探索异质性和多效性的存在，我们还进行了彻底的敏感性分析。结果:我们发现36免疫细胞与肝癌有关,CD64 CD14 - CD16 +单核细胞(OR = 1.328, 95% CI = 1.116 - 1.581, p = 0.001), CD3 -淋巴细胞淋巴细胞百分比(OR = 1.341, 95% CI = 1.027 - 1.750, p = 0.031),在CD14 +单核细胞HLA DR (OR = 1.256, 95% CI = 1.089 - 1.448, p = 0.002), CD19在等离子Blast-Plasma CD19细胞(OR = 1.224, 95% CI = 1.073 - 1.396, p = 0.003), CCR2在单核细胞(OR = 1.204, 95% CI = 1.073 - 1.351, p = 0.002)和幼稚的CD4 + T细胞绝对计数(或= 0.797,95% CI = 0.655 ~ 0.969, p = 0.023)与HCC的相关性最强。其中CD14- CD16+单核细胞上的CD64、CD3 -淋巴细胞%淋巴细胞上的CD64、CD14+单核细胞上的HLA DR、Plasma Blast-Plasma Cells上的CD19是HCC的危险因素，Naive CD4+ T细胞绝对计数是HCC的保护因素。结论：我们对免疫细胞和HCC作用的MR分析为了解循环免疫状态提供了一个框架。肝细胞癌浸润免疫细胞的系统分析可以帮助剖析肝细胞癌的免疫状态，评估当前检查点阻断剂的使用，最重要的是，有助于开发创新的免疫疗法。需要进一步的研究来验证这些发现，并探索影响HCC免疫反应的潜在机制。
The causal relationship between immune cells and hepatocellular carcinoma: a Mendelian randomization (MR).
Objective: Hepatocellular carcinoma (HCC) is a complex and multifaceted disease that is increasingly prevalent globally. The involvement of immune cells in the tumour microenvironment has been linked to the progression of HCC, but the exact cause-and-effect relationship is not yet clear. In this study, we utilise Mendelian randomization (MR) to investigate the potential causal links between immune factors and the development of HCC.
Method: We executed a comprehensive MR study, leveraging publicly accessible genetic datasets to explore the potential causal links between 731 types of immune cells and HCC. Our analysis primarily applied inverse variance weighting and weighted median methods. To evaluate the robustness of our findings and probe for the presence of heterogeneity and pleiotropy, we also conducted thorough sensitivity analyses.
Results: We found 36 immune cells were associated with HCC, CD64 on CD14- CD16+ monocytes (OR = 1.328, 95% CI = 1.116- 1.581, p = 0.001), CD3- lymphocyte %lymphocytes (OR = 1.341, 95% CI = 1.027- 1.750, p = 0.031), HLA DR on CD14+ monocytes (OR = 1.256, 95% CI = 1.089- 1.448, p = 0.002), CD19 on CD19 on Plasma Blast-Plasma Cell (OR = 1.224, 95% CI = 1.073- 1.396, p = 0.003), CCR2 on monocytes (OR = 1.204, 95% CI = 1.073- 1.351, p = 0.002) and Naive CD4+ T cell Absolute Count (OR = 0.797, 95% CI = 0.655- 0.969, p = 0.023) were the most strongly associated with HCC. Among them, CD64 on CD14- CD16+ monocytes, CD3 - lymphocyte %lymphocytes, HLA DR on CD14+ monocytes and CD19 on Plasma Blast-Plasma Cells are the risk factors, while Naive CD4+ T cell Absolute Count are protective factors for HCC.
Conclusion: Our MR analysis of the role of immune cells and HCC provides a framework for knowledge of circulating immune status. Systematic assays of infiltrating immune cells in HCC can help dissect the immune status of HCC, assess the current use of checkpoint blockers, and most importantly, aid in the development of innovative immunotherapies. Further research is necessary to validate these findings and explore the underlying mechanisms that influence the immune response to HCC.
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