PMID- 35693827
OWN - NLM
STAT- MEDLINE
DCOM- 20220614
LR  - 20220716
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 13
DP  - 2022
TI  - Comprehensive Molecular Analyses of a Macrophage-Related Gene Signature With 
      Regard to Prognosis, Immune Features, and Biomarkers for Immunotherapy in 
      Hepatocellular Carcinoma Based on WGCNA and the LASSO Algorithm.
PG  - 843408
LID - 10.3389/fimmu.2022.843408 [doi]
LID - 843408
AB  - Macrophages have been reported to exert a crucial role in hepatocellular 
      carcinoma (HCC). This study aimed to explore the macrophage-related genes and 
      establish a macrophage-related signature (MRS) model to predict the overall 
      survival (OS) of patients with HCC based on these genes' expression. We screened 
      the macrophage-related gene module by weighted gene coexpression network analysis 
      (WGCNA), the least absolute shrinkage and selection operator (LASSO) Cox 
      regression analysis was utilized for further selection, and the selected genes 
      were entered into stepwise regression to develop the MRS model, which was further 
      validated in the Gene Expression Omnibus (GEO) and International Cancer Genome 
      Consortium (ICGC) datasets. We analyzed the biological phenotypes associated with 
      macrophages in terms of functional enrichment, tumor immune signature, and tumor 
      mutational signature. The patient's response to immunotherapy was inferred by the 
      tumor immune dysfunction and exclusion (TIDE) score, the immunophenotype score 
      (IPS), and the IMvigor210 dataset. A novel MRS model was established based on the 
      LASSO regression coefficients of the genes PON1, IL15RA, NEIL3, HILPDA, PFN2, 
      HAVCR1, ANXA10, CDCA8, EPO, S100A9, TTK, KLRB1, SPP1, STC2, CYP26B1, GPC1, G6PD, 
      and CBX2. In either dataset, MRS was identified as an independent risk factor for 
      OS in HCC patients. Additionally, our research indicated that a high-risk score 
      in the MRS model was significantly correlated with tumor staging, pathological 
      grade, tumor-node-metastasis (TNM) stage, and survival. Several genes of the 
      human leukocyte antigen (HLA) family and immune checkpoints were highly expressed 
      in the high-risk group. In addition, the frequency of tumor mutations was also 
      higher in the high-risk group. According to our analyses, a higher risk score in 
      the MRS model may predict a better response to immunotherapy.
CI  - Copyright (c) 2022 Wang, Dai, Shen, Yang, Yang, Yang, Qiu and Wang.
FAU - Wang, Tao
AU  - Wang T
AD  - Department of Liver Surgery and Liver Transplantation Center, West China Hospital 
      of Sichuan University, Chengdu, China.
AD  - State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, 
      Sichuan University, Chengdu, China.
FAU - Dai, Liqun
AU  - Dai L
AD  - State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, 
      Sichuan University, Chengdu, China.
FAU - Shen, Shu
AU  - Shen S
AD  - Department of Liver Surgery and Liver Transplantation Center, West China Hospital 
      of Sichuan University, Chengdu, China.
FAU - Yang, Yi
AU  - Yang Y
AD  - Department of Liver Surgery and Liver Transplantation Center, West China Hospital 
      of Sichuan University, Chengdu, China.
FAU - Yang, Ming
AU  - Yang M
AD  - Department of Liver Surgery and Liver Transplantation Center, West China Hospital 
      of Sichuan University, Chengdu, China.
FAU - Yang, Xianwei
AU  - Yang X
AD  - Department of Thyroid Surgery, Sichuan Provincial People's Hospital, University 
      of Electronic Science and Technology of China, Chengdu, China.
FAU - Qiu, Yiwen
AU  - Qiu Y
AD  - Department of Liver Surgery and Liver Transplantation Center, West China Hospital 
      of Sichuan University, Chengdu, China.
FAU - Wang, Wentao
AU  - Wang W
AD  - Department of Liver Surgery and Liver Transplantation Center, West China Hospital 
      of Sichuan University, Chengdu, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220527
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (PFN2 protein, human)
RN  - 0 (Profilins)
RN  - EC 3.1.8.1 (Aryldialkylphosphatase)
RN  - EC 3.1.8.1 (PON1 protein, human)
SB  - IM
MH  - Algorithms
MH  - Aryldialkylphosphatase
MH  - Biomarkers, Tumor/genetics/metabolism
MH  - *Carcinoma, Hepatocellular/genetics/therapy
MH  - Gene Expression Regulation, Neoplastic
MH  - Gene Regulatory Networks
MH  - Humans
MH  - Immunotherapy
MH  - *Liver Neoplasms/genetics/therapy
MH  - Macrophages/metabolism
MH  - Profilins/genetics
MH  - Prognosis
PMC - PMC9186446
OTO - NOTNLM
OT  - hepatocellular carcinoma (HCC)
OT  - immune drug response
OT  - immunity
OT  - macrophage-related genes
OT  - prognosis
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/06/14 06:00
MHDA- 2022/06/15 06:00
PMCR- 2022/01/01
CRDT- 2022/06/13 03:21
PHST- 2021/12/25 00:00 [received]
PHST- 2022/04/19 00:00 [accepted]
PHST- 2022/06/13 03:21 [entrez]
PHST- 2022/06/14 06:00 [pubmed]
PHST- 2022/06/15 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2022.843408 [doi]
PST - epublish
SO  - Front Immunol. 2022 May 27;13:843408. doi: 10.3389/fimmu.2022.843408. eCollection 
      2022.