PT - JOURNAL ARTICLE AU - Huan Liu AU - Ronghua Zhao AU - Rongrong Qin AU - Haoyu Sun AU - Qiang Huang AU - Lianxin Liu AU - Zhigang Tian AU - Björn Nashan AU - Cheng Sun AU - Rui Sun TI - Panoramic comparison between NK cells in healthy and cancerous liver through single-cell RNA sequencing AID - 10.20892/j.issn.2095-3941.2022.0050 DP - 2022 Jul 21 TA - Cancer Biology & Medicine PG - 20220050 4099 - http://www.cancerbiomed.org/content/early/2022/07/21/j.issn.2095-3941.2022.0050.short 4100 - http://www.cancerbiomed.org/content/early/2022/07/21/j.issn.2095-3941.2022.0050.full AB - 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.