Full Text | PDF

J Cancer 2024; 15(13):4219-4231. doi:10.7150/jca.96744 This issue Cite

Research Paper

Causal relationship between immune cells and hepatocellular carcinoma: a Mendelian randomisation study

Jingyi Tang^1,2,3,*, Shengke Zhang^3,*, Lai Jiang^3,*, Jie Liu^1,2,4,*, Jiayu Xu⁵, Chenglu Jiang³, Zipei Chen³, Xuancheng Zhou³, Claire Fuller⁶, Jinbang Huang³, Haiqing Chen³, Guanhu Yang⁷, Changsong Bai⁸, Defeng Yin^9,10,✉, Bo Li^1,2,✉, Hao Chi^3,8,✉

1. Department of General Surgery (Hepatopancreatobiliary surgery), The Affiliated Hospital, Southwest Medical University, Luzhou 646000, China.
2. Academician (Expert) Workstation of Sichuan Province, Metabolic Hepatobiliary and Pancreatic Diseases Key Laboratory of Luzhou City, The Affiliated Hospital, Southwest Medical University, Sichuan, China.
3. Department of Clinical Medicine, Southwest Medical University, Luzhou 646000, China.
4. Department of General Surgery, Dazhou Central Hospital, Dazhou 635000, China.
5. School of Science, Minzu University of China, Beijing, 100081 China.
6. Department of Chemical and Biomolecular Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
7. Department of Specialty Medicine, Ohio University, Athens 45701, OH, USA.
8. Department of General Surgery, Xuyong People's Hospital, Luzhou, China.
9. Department of Emergency Medicine, The Affiliated Hospital, Southwest Medical University, 646000 Luzhou, China.
10. Department of Emergency Medicine, Xuyong People's Hospital, Luzhou, China.
*These authors have contributed equally to this work.

✉ Corresponding authors: yindefeng104edu.cn (Defeng Yin); liboer2002com (Bo Li); Chihao7511com (Hao Chi).

Abstract

Background: Hepatocellular carcinoma (HCC), the predominant malignancy of the digestive tract, ranks as the third most common cause of cancer-related mortality globally, significantly impeding human health and lifespan. Emerging immunotherapeutic approaches have ignited fresh optimism for patient outcomes. This investigation probes the link between 731 immune cell phenotypes and HCC through Mendelian Randomization and single-cell sequencing, aiming to unearth viable drug targets and dissect HCC's etiology.

Methods: We conducted an exhaustive two-sample Mendelian Randomization analysis to ascertain the causal links between immune cell features and HCC, utilizing publicly accessible genetic datasets to explore the causal connections of 731 immune cell traits with HCC susceptibility. The integrity, diversity, and potential horizontal pleiotropy of these findings were rigorously assessed through extensive sensitivity analyses. Furthermore, single-cell sequencing was employed to penetrate the pathogenic underpinnings of HCC.

Results: Establishing a significance threshold of pval_Inverse.variance.weighted at 0.05, our study pinpointed five immune characteristics potentially elevating HCC risk: B cell % CD3- lymphocyte (TBNK panel), CD25 on IgD+ (B cell panel), HVEM on TD CD4+ (Maturation stages of T cell panel), CD14 on CD14+ CD16- monocyte (Monocyte panel), CD4 on CD39+ activated Treg ( Treg panel). Conversely, various cellular phenotypes tied to BAFF-R expression emerged as protective elements. Single-cell sequencing unveiled profound immune cell phenotype interactions, highlighting marked disparities in cell communication and metabolic activities.

Conclusion: Leveraging MR and scRNA-seq techniques, our study elucidates potential associations between 731 immune cell phenotypes and HCC, offering a window into the molecular interplays among cellular phenotypes, and addressing the limitations of mono-antibody therapeutic targets.

Keywords: HCC, 731 immune traits, Mendelian Randomization, Single-cell RNA sequence, Pseudo-time analysis, Tumor microenvironment

Citation styles

©2024 Ivyspring International Publisher. Terms of use