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This study quantifies immune cell subsets by flow cytometry and profiles PBL transcriptomes using 10× single-cell sequencing, supported by GEO-derived cases and R-based bioinformatics. Elevated NK and CD8+ T cells differentiate ICC/HCC from benign liver disease, and both associate with recurrence-free survival in a multivariate Cox model. Single-cell data reveal TGFβ signaling downregulation in tumor-derived CD8+ T cells, alongside selenium metabolism dysregulation, with SELENBP1 upregulation and SEPP1 reduction. Overall, primary liver cancer reshapes PBL composition and selenoprotein metabolism.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/peripheral-lymphocytes-in-primary-liver-cancers-elevated-nk-and-cd8-t-cells-and-dysregulated-selenium-metabolism/337498/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/peripheral-lymphocytes-in-primary-liver-cancers-elevated-nk-and-cd8-t-cells-and-dysregulated-selenium-metabolism/337498.png","ImageObject",300,407,{"name":92,"@type":93},"Anda","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-27","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",13,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"How are peripheral blood lymphocytes analyzed in this study?","Question",{"text":113,"@type":114},"Flow cytometry quantifies immune cell populations, while PBL transcriptomes are analyzed using 10× single-cell sequencing. GEO datasets are also incorporated for further investigation.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"Which lymphocyte subsets are elevated in primary liver cancers?",{"text":118,"@type":114},"NK cells and CD8+ T cells are elevated in both ICC and HCC compared with benign liver disease.",{"name":120,"@type":111,"acceptedAnswer":121},"What molecular immune and selenium-related changes are reported?",{"text":122,"@type":114},"Tumor-derived CD8+ T cells show downregulation of TGFβ signaling, and selenium metabolism is dysregulated. 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Peripheral Lymphocytes in Primary Liver Cancers: Elevated NK and CD8+ T Cells and Dysregulated Selenium Metabolism. Biomolecules 2024, 14, 222 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)biom14020222  \nAcademic Editors: Wei Zhong and Jorge Joven  \nReceived: 16 January 2024  \nRevised: 8 February 2024  \nAccepted: 10 February 2024  \nPublished: 14 February 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 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; [zhoucheng16@fudan.edu.cn](zhoucheng16@fudan.edu.cn) (C.Z.); [21111210106@m.fudan.edu.cn](21111210106@m.fudan.edu.cn) (B.S.)  \n2 Department of Anesthesia, Zhongshan Hospital, Fudan University, Shanghai 200032, China; [lu.zhufeng@zs-hospital.sh.cn](lu.zhufeng@zs-hospital.sh.cn)  \n3 Department of Hepatic Oncology, Xiamen Clinical Research Center for Cancer Therapy, Zhongshan Hospital, Fudan University (Xiamen Branch), Xiamen 361015, China  \n4 Center for Evidence-Based Medicine, Shanghai Medical School, Fudan University, Shanghai 200032, China  \n* [Correspondence: wang.zheng@zs-hospital.sh.cn](Correspondence: wang.zheng@zs-hospital.sh.cn) (Z.W.); [qiu.shuangjian@zs-hospital.sh.cn](qiu.shuangjian@zs-hospital.sh.cn) (S.-J.Q.)† These authors contributed equally to this work.  \nAbstract: 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 aberrationsin 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.  \nKeywords: primary liver cancer; peripheral blood lymphocytes; SELENBP1; SEPP1  \n1. Introduction  \nPrimary liver cancer (PLC), which is the third leading cause of cancer mortality, is classified into hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and combined hepatocellular-cholangiocarcinoma by pathology [1] . The former two types account for 99% of PLC, while combined hepatocellular-cholangiocarcinoma is generally considered to be a combinat","cbCaigVD72ZKk4My","https://ap.wps.com/l/cbCaigVD72ZKk4My","pdf",4342580,14,"English","# Abstract\n# Introduction\n## Background and classification of primary liver cancer\n## Immune relevance and limited study of peripheral lymphocytes\n## Systemic therapies and T cell exhaustion\n## Role of single-cell sequencing technology","[{\"question\":\"How are peripheral blood lymphocytes analyzed in this study?\",\"answer\":\"Flow cytometry quantifies immune cell populations, while PBL transcriptomes are analyzed using 10× single-cell sequencing. GEO datasets are also incorporated for further investigation.\"},{\"question\":\"Which lymphocyte subsets are elevated in primary liver cancers?\",\"answer\":\"NK cells and CD8+ T cells are elevated in both ICC and HCC compared with benign liver disease.\"},{\"question\":\"What molecular immune and selenium-related changes are reported?\",\"answer\":\"Tumor-derived CD8+ T cells show downregulation of TGFβ signaling, and selenium metabolism is dysregulated. Proteomic results indicate increased SELENBP1 and decreased SEPP1 after tumor resection.\"}]","Peripheral Lymphocytes in Primary Liver Cancers - Elevated NK and CD8+ T Cells and Dysregulated Selenium Metabolism | PDF",1790019347,35]