Objective: NK cells play crucial roles in the immune defense mechanisms against viral infections and transformed cells. However, the developmental progression, transcriptomic landscape, and functional subtypes of liver NK cells are not well defined. Hepatocellular carcinoma (HCC) accounts for approximately 80％ of primary liver cancer worldwide, yet the biological characteristics of NK cells in the HCC environment are unclear. Therefore, we aimed to determine these cells' roles in tumorigenesis and prognosis. Methods: We compared the single-cell RNA sequencing profiles of NK cells purified from blood (n = 1), healthy liver tissues (n = 3), HCC tumor tissues (n = 4), and peritumor liver tissues (n = 1) to identify NK cell subsets. Furthermore, we performed bioinformatics analysis by using The Cancer Genome Atlas (TCGA) data to identify prognostic biomarkers simultaneously overexpressed in the blood and tumor tissues of patients with HCC. Results: Transcriptomic analysis revealed 5 NK cell subsets (L1-NK-CD56bright, L2-NK-CD56dim, L3-NK-HLA, L4-LrNK-FCGR3A, and L5-LrNK-XCL1) in the healthy liver tissues. However, the transitional L3 subset and the CXCR6+CD16+ L4 subset with strong anti-tumor activity were absent in the HCC and peritumor liver tissues. Furthermore, 4 common prognosis-associated genes (RHOB, TALDO1, HLA-DPA1, and TKT) were significantly overexpressed in the paired tumor tissue and blood. Conclusions: Our study revealed 5 specific subsets of NK cells in healthy human liver tissues. However, only 3 of the 5 NK cell subsets were present in HCC and peritumor tissues. The cytotoxic NK cell subsets were absent in HCC tissues. Furthermore, we identified 4 potential non-invasive prognostic biomarkers in patients with HCC.

Huan Liu;Ronghua Zhao;Rongrong Qin;Haoyu Sun;Qiang Huang;Lianxin Liu;Zhigang Tian;Bj?rn Nashan;Cheng Sun;Rui Sun

The First Affiliated Hospital of USTC,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei 230001,China;The CAS Key Laboratory of Innate Immunity and Chronic Disease,School of Basic Medical Sciences,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei 230027,China;Institute of Immunology,University of Science and Technology of China,Hefei 230027,China

癌症生物学与医学（英文版）

[1]Huan Liu;Ronghua Zhao;Rongrong Qin;Haoyu Sun;Qiang Huang;Lianxin Liu;Zhigang Tian;Bj?rn Nashan;Cheng Sun;Rui Sun-.Panoramic comparison between NK cells in healthy and cancerous liver through single-cell RNA sequencing)[J].癌症生物学与医学（英文版）,2022(09):1334-1351

peritumor,CD56dim,LrNK,XCL1,CXCR6+CD16+

Panoramic,comparison,between,cells,healthy,cancerous,liver,through,single,sequencing,Objective,play,crucial,roles,immune,defense,mechanisms,against,viral,infections,transformed,However,developmental,progression,transcriptomic,landscape,functional,subtypes,not,well,defined,Hepatocellular,carcinoma,HCC,accounts,approximately,primary,worldwide,yet,biological,characteristics,environment,unclear,Therefore,aimed,determine,these,tumorigenesis,prognosis,Methods,We,compared,profiles,purified,from,blood,tissues,identify,subsets,Furthermore,performed,bioinformatics,analysis,by,using,Cancer,Genome,Atlas,TCGA,data,prognostic,biomarkers,simultaneously,overexpressed,patients,Results,Transcriptomic,revealed,CD56bright,L2,L3,HLA,L4,FCGR3A,L5,transitional,strong,anti,activity,were,absent,common,associated,RHOB,TALDO1,DPA1,TKT,significantly,paired,Conclusions,Our,study,specific,human,only,present,cytotoxic,identified,potential,invasive

0.478389