RT Journal Article
SR Electronic
T1 Panoramic comparison between NK cells in healthy and cancerous liver through single-cell RNA sequencing
JF Cancer Biology & Medicine
JO Cancer Biology & Medicine
FD China Anti-Cancer Association
SP 20220050
DO 10.20892/j.issn.2095-3941.2022.0050
A1 Huan Liu
A1 Ronghua Zhao
A1 Rongrong Qin
A1 Haoyu Sun
A1 Qiang Huang
A1 Lianxin Liu
A1 Zhigang Tian
A1 Björn Nashan
A1 Cheng Sun
A1 Rui Sun
YR 2022
UL http://www.cancerbiomed.org/content/early/2022/07/21/j.issn.2095-3941.2022.0050.abstract
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.