Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Department of Anesthesia, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Biomolecules. 2024 Feb 14;14(2):222. doi: 10.3390/biom14020222.
Peripheral blood lymphocytes (PBLs), which play a pivotal role in orchestrating the immune system, garner minimal attention in hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). The impact of primary liver cancers on PBLs remains unexplored. In this study, flow cytometry facilitated the quantification of cell populations, while transcriptome of PBLs was executed utilizing 10× single-cell sequencing technology. Additionally, pertinent cases were curated from the GEO database. Subsequent bioinformatics and statistical analyses were conducted utilizing R (4.2.1) software. Elevated counts of NK cells and CD8+ T cells were observed in both ICC and HCC when compared to benign liver disease (BLD). In the multivariate Cox model, NK cells and CD8+ T cells emerged as independent risk factors for recurrence-free survival. Single-cell sequencing of PBLs uncovered the downregulation of TGFβ signaling in tumor-derived CD8+ T cells. Pathway enrichment analysis, based on differential expression profiling, highlighted aberrations in selenium metabolism. Proteomic analysis of preoperative and postoperative peripheral blood samples from patients undergoing tumor resection revealed a significant upregulation of SELENBP1 and a significant downregulation of SEPP1. Primary liver cancer has a definite impact on PBLs, manifested by alterations in cellular quantities and selenoprotein metabolism.
外周血淋巴细胞 (PBLs) 在调节免疫系统中起着关键作用,但在肝细胞癌 (HCC) 和肝内胆管癌 (ICC) 中却很少受到关注。原发性肝癌对 PBLs 的影响尚未得到探索。在这项研究中,流式细胞术有助于量化细胞群体,同时利用 10×单细胞测序技术对 PBLs 的转录组进行分析。此外,还从 GEO 数据库中整理了相关病例。随后利用 R(4.2.1)软件进行生物信息学和统计学分析。与良性肝病 (BLD) 相比,ICC 和 HCC 中 NK 细胞和 CD8+T 细胞的计数均升高。在多变量 Cox 模型中,NK 细胞和 CD8+T 细胞是无复发生存的独立危险因素。PBLs 的单细胞测序揭示了肿瘤衍生的 CD8+T 细胞中 TGFβ 信号的下调。基于差异表达谱的通路富集分析突出了硒代谢的异常。对接受肿瘤切除的患者术前和术后外周血样本的蛋白质组学分析显示,SELENBP1 显著上调,SEPP1 显著下调。原发性肝癌对 PBLs 有明确的影响,表现为细胞数量和硒蛋白代谢的改变。