PMID- 37030269
OWN - NLM
STAT- MEDLINE
DCOM- 20230421
LR  - 20230421
IS  - 1879-0534 (Electronic)
IS  - 0010-4825 (Linking)
VI  - 158
DP  - 2023 May
TI  - Deciphering the immune heterogeneity dominated by natural killer cells with 
      prognostic and therapeutic implications in hepatocellular carcinoma.
PG  - 106872
LID - S0010-4825(23)00337-2 [pii]
LID - 10.1016/j.compbiomed.2023.106872 [doi]
AB  - Belonging to type 1 innate lymphoid cells (ILC1), natural killer (NK) cells play 
      an important role not only in fighting microbial infections but also in 
      anti-tumor response. Hepatocellular carcinoma (HCC) represents an 
      inflammation-related malignancy and NK cells are enriched in the liver, making 
      them an essential component of the HCC immune microenvironment. In this study, we 
      performed single-cell RNA-sequencing (scRNA-seq) analysis to identify the NK cell 
      marker genes (NKGs) and uncovered 80 prognosis-related ones by the TCGA-LIHC 
      dataset. Based on prognostic NKGs, HCC patients were categorized into two 
      subtypes with distinct clinical outcomes. Subsequently, we conducted LASSO-COX 
      and stepwise regression analysis on prognostic NKGs to establish a five-gene 
      (UBB, CIRBP, GZMH, NUDC, and NCL) prognostic signature-NKscore. Different 
      mutation statuses of the two risk groups stratified by NKscore were 
      comprehensively characterized. Besides, the established NKscore-integrated 
      nomogram presented enhanced predictive performance. Single sample gene set 
      enrichment analysis (ssGSEA) analysis was used to uncover the landscape of the 
      tumor immune microenvironment (TIME) and the high-NKscore risk group was 
      characterized with an immune-exhausted phenotype while the low-NKscore risk group 
      held relatively strong anti-cancer immunity. T cell receptor (TCR) repertoire, 
      tumor inflammation signature (TIS), and Immunophenoscore (IPS) analyses revealed 
      differences in immunotherapy sensitivity between the two NKscore risk groups. 
      Taken together, we developed a novel NK cell-related signature to predict the 
      prognosis and immunotherapy efficacy for HCC patients.
CI  - Copyright (c) 2023 Elsevier Ltd. All rights reserved.
FAU - Guo, Chengbin
AU  - Guo C
AD  - Faculty of Medicine, Macau University of Science and Technology, Tapai, Macau, 
      999078, China.
FAU - Tang, Yuqin
AU  - Tang Y
AD  - Clinical Bioinformatics Experimental Center, Henan Provincial People's Hospital, 
      Zhengzhou University, 450003, Zhengzhou, China.
FAU - Li, Qizhuo
AU  - Li Q
AD  - School of Computer Science and Engineering, Sun Yat-sen University, Guangzhou, 
      510006, China.
FAU - Yang, Zhao
AU  - Yang Z
AD  - West China School of Medicine, West China Hospital, Sichuan University, Chengdu, 
      610041, China.
FAU - Guo, Yuqi
AU  - Guo Y
AD  - Clinical Bioinformatics Experimental Center, Henan Provincial People's Hospital, 
      Zhengzhou University, 450003, Zhengzhou, China. Electronic address: 
      yuqiguo@zzu.edu.cn.
FAU - Chen, Chuanliang
AU  - Chen C
AD  - Clinical Bioinformatics Experimental Center, Henan Provincial People's Hospital, 
      Zhengzhou University, 450003, Zhengzhou, China. Electronic address: 
      henanccl@163.com.
FAU - Zhang, Yongqiang
AU  - Zhang Y
AD  - West China School of Medicine, West China Hospital, Sichuan University, Chengdu, 
      610041, China; Guangzhou Women and Children's Medical Center, Guangzhou Medical 
      University, Guangzhou, 510623, China. Electronic address: zyq1014zyq1014@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230404
PL  - United States
TA  - Comput Biol Med
JT  - Computers in biology and medicine
JID - 1250250
RN  - 0 (CIRBP protein, human)
RN  - 0 (RNA-Binding Proteins)
SB  - IM
MH  - Humans
MH  - Prognosis
MH  - *Carcinoma, Hepatocellular/genetics/therapy
MH  - Immunity, Innate
MH  - *Liver Neoplasms/genetics/therapy
MH  - Inflammation
MH  - Killer Cells, Natural
MH  - Tumor Microenvironment
MH  - RNA-Binding Proteins
OTO - NOTNLM
OT  - Hepatocellular carcinoma
OT  - Immune heterogeneity
OT  - Natural killer cell
OT  - Prognosis
OT  - Therapeutic response
COIS- Conflict of interest The authors have declared that no competing interest exists.
EDAT- 2023/04/09 06:00
MHDA- 2023/04/21 06:41
CRDT- 2023/04/08 18:11
PHST- 2023/02/06 00:00 [received]
PHST- 2023/03/15 00:00 [revised]
PHST- 2023/03/30 00:00 [accepted]
PHST- 2023/04/21 06:41 [medline]
PHST- 2023/04/09 06:00 [pubmed]
PHST- 2023/04/08 18:11 [entrez]
AID - S0010-4825(23)00337-2 [pii]
AID - 10.1016/j.compbiomed.2023.106872 [doi]
PST - ppublish
SO  - Comput Biol Med. 2023 May;158:106872. doi: 10.1016/j.compbiomed.2023.106872. Epub 
      2023 Apr 4.