PMID- 34108619
OWN - NLM
STAT- MEDLINE
DCOM- 20211221
LR  - 20221030
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Linking)
VI  - 40
IP  - 26
DP  - 2021 Jul
TI  - A risk model developed based on tumor microenvironment predicts overall survival 
      and associates with tumor immunity of patients with lung adenocarcinoma.
PG  - 4413-4424
LID - 10.1038/s41388-021-01853-y [doi]
AB  - Tumor microenvironment (TME) has been reported to exhibit a crucial effect in 
      lung cancer. Therefore, this study was aimed to investigate the genes associated 
      with TME and develop a risk score to predict the overall survival (OS) of 
      patients with lung adenocarcinoma (LUAD) based on these genes. The immune and 
      stromal scores were generated by the ESTIMATE algorithm for LUAD patients in The 
      Cancer Genome Atlas (TCGA) database. Differentially expressed gene and weighted 
      gene co-expression network analyses were used to derive immune- and 
      stromal-related genes. The Least Absolute Shrinkage and Selection Operator 
      (LASSO)-Cox regression was applied for further selection and the selected genes 
      were inputted into stepwise regression to develop TME-related risk score 
      (TMErisk) which was further validated in Gene Expression Omnibus (GEO) datasets. 
      TMErisk-related biological phenotypes were analyzed in function enrichment, tumor 
      immune signature, and tumor mutation signature. The patient's response to 
      immunotherapy was inferred by the tumor immune dysfunction and exclusion (TIDE) 
      score and immunophenoscore (IPS). According to our results, TMErisk was developed 
      based on SERPINE1, CX3CR1, CD200R1, GBP1, IRF1, STAP1, LOX, and OR7E47P. 
      Furthermore, high TMErisk was identified as a poor factor for OS in TCGA and GEO 
      datasets, as well as in subgroup analysis with different gender, smoking status, 
      age, race, anatomic site, therapies, and tumor-node-metastasis (TNM) stages. 
      Higher TMErisk is also associated negatively with the abundance of B cells, 
      CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and other stromal or immune 
      cells. Several genes of the human leukocyte antigen (HLA) family and immune 
      checkpoints were less expressed in the high-TMErisk group. Mutations of 19 genes 
      occurred more frequently in the high-TMErisk group. These mutations may be 
      associated with TME change and indicate patients' response to immunotherapy. 
      According to our analyses, a lower TMErisk score may indicate better response and 
      OS outcome of immunotherapy.
FAU - Wu, Jie
AU  - Wu J
AD  - Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China.
FAU - Li, Lan
AU  - Li L
AD  - Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China.
FAU - Zhang, Huibo
AU  - Zhang H
AD  - Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China.
FAU - Zhao, Yaqi
AU  - Zhao Y
AD  - Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China.
FAU - Zhang, Haohan
AU  - Zhang H
AD  - Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China.
FAU - Wu, Siyi
AU  - Wu S
AD  - Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China.
FAU - Xu, Bin
AU  - Xu B
AUID- ORCID: 0000-0002-0499-0430
AD  - Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China. 
      xubin_oncology@whu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210609
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Biomarkers, Tumor)
SB  - IM
MH  - Adenocarcinoma of Lung/genetics/immunology/mortality/pathology
MH  - Biomarkers, Tumor/genetics
MH  - Gene Expression Regulation, Neoplastic/genetics/immunology
MH  - Humans
MH  - Immunity/genetics/*immunology
MH  - Immunotherapy/methods
MH  - Lung Neoplasms/genetics/*immunology/*mortality/pathology
MH  - Mutation/genetics
MH  - Prognosis
MH  - Tumor Microenvironment/genetics/*immunology
EDAT- 2021/06/11 06:00
MHDA- 2021/12/22 06:00
CRDT- 2021/06/10 06:36
PHST- 2020/03/11 00:00 [received]
PHST- 2021/05/21 00:00 [accepted]
PHST- 2021/05/10 00:00 [revised]
PHST- 2021/06/11 06:00 [pubmed]
PHST- 2021/12/22 06:00 [medline]
PHST- 2021/06/10 06:36 [entrez]
AID - 10.1038/s41388-021-01853-y [pii]
AID - 10.1038/s41388-021-01853-y [doi]
PST - ppublish
SO  - Oncogene. 2021 Jul;40(26):4413-4424. doi: 10.1038/s41388-021-01853-y. Epub 2021 
      Jun 9.