PMID- 33314730
OWN - NLM
STAT- MEDLINE
DCOM- 20210719
LR  - 20210719
IS  - 2045-7634 (Electronic)
IS  - 2045-7634 (Linking)
VI  - 10
IP  - 3
DP  - 2021 Feb
TI  - Immune landscape and a promising immune prognostic model associated with TP53 in 
      early-stage lung adenocarcinoma.
PG  - 806-823
LID - 10.1002/cam4.3655 [doi]
AB  - PURPOSE: TP53 mutation, one of the most frequent mutations in early-stage lung 
      adenocarcinoma (LUAD), triggers a series of alterations in the immune landscape, 
      progression, and clinical outcome of early-stage LUAD. Our study was designed to 
      unravel the effects of TP53 mutation on the immunophenotype of early-stage LUAD 
      and formulate a TP53-associated immune prognostic model (IPM) that can estimate 
      prognosis in early-stage LUAD patients. MATERIALS AND METHODS: Immune-associated 
      differentially expressed genes (DEGs) between TP53 mutated (TP53(MUT) ) and TP53 
      wild-type (TP53(WT) ) early-stage LUAD were comprehensively analyzed. Univariate 
      Cox analysis and least absolute shrinkage and selection operator (LASSO) analysis 
      identified the prognostic immune-associated DEGs. We constructed and validated an 
      IPM based on the TCGA and a meta-GEO composed of GSE72094, GSE42127, and 
      GSE31210, respectively. The CIBERSORT algorithm was analyzed for assessing the 
      percentage of immune cell types. A nomogram model was established for clinical 
      application. RESULTS: TP53 mutation occurred in approximately 50.00% of LUAD 
      patients, stimulating a weakened immune response in early-stage LUAD. Sixty-seven 
      immune-associated DEGs were determined between TP53(WT) and TP53(MUT) cohort. An 
      IPM consisting of two prognostic immune-associated DEGs (risk 
      score = 0.098 * ENTPD2 expression + 0.168 * MIF expression) was developed through 
      397 cases in the TCGA and further validated based on 623 patients in a meta-GEO. 
      The IPM stratified patients into low or high risk of undesirable survival and was 
      identified as an independent prognostic indicator in multivariate analysis 
      (HR = 2.09, 95% CI: 1.43-3.06, p < 0.001). Increased expressions of PD-L1, 
      CTLA-4, and TIGIT were revealed in the high-risk group. Prognostic nomogram 
      incorporating the IPM and other clinicopathological parameters (TNM stage and 
      age) achieved optimal predictive accuracy and clinical utility. CONCLUSION: The 
      IPM based on TP53 status is a reliable and robust immune signature to identify 
      early-stage LUAD patients with high risk of unfavorable survival.
CI  - (c) 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
FAU - Wu, Chengde
AU  - Wu C
AD  - Department of Thoracic Surgery, Affiliated Haikou Hospital of Xiangya Medical 
      College, Central South University, Haikou, Hainan, China.
FAU - Rao, Xiang
AU  - Rao X
AD  - Department of Pathology, Affiliated Haikou Hospital of Xiangya Medical College, 
      Central South University, Haikou, Hainan, China.
FAU - Lin, Wei
AU  - Lin W
AUID- ORCID: 0000-0001-9598-7474
AD  - Department of Thoracic Surgery, Affiliated Haikou Hospital of Xiangya Medical 
      College, Central South University, Haikou, Hainan, China.
LA  - eng
PT  - Journal Article
DEP - 20201212
PL  - United States
TA  - Cancer Med
JT  - Cancer medicine
JID - 101595310
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (TP53 protein, human)
RN  - 0 (Tumor Suppressor Protein p53)
SB  - IM
MH  - Adenocarcinoma of Lung/immunology/metabolism/*pathology/therapy
MH  - Biomarkers, Tumor/immunology/*metabolism
MH  - Databases, Genetic
MH  - Female
MH  - Follow-Up Studies
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Lung Neoplasms/immunology/metabolism/*pathology/therapy
MH  - Male
MH  - Middle Aged
MH  - Mutation
MH  - *Nomograms
MH  - Prognosis
MH  - ROC Curve
MH  - Retrospective Studies
MH  - Survival Rate
MH  - Transcriptome
MH  - Tumor Suppressor Protein p53/genetics/*metabolism
PMC - PMC7897963
OTO - NOTNLM
OT  - CIBERSORT
OT  - TP53
OT  - early-stage lung adenocarcinoma
OT  - immune prognostic model
OT  - prognosis
COIS- The authors have declared that no competing interest exists.
EDAT- 2020/12/15 06:00
MHDA- 2021/07/20 06:00
PMCR- 2020/12/12
CRDT- 2020/12/14 11:17
PHST- 2020/08/23 00:00 [received]
PHST- 2020/11/01 00:00 [revised]
PHST- 2020/11/26 00:00 [accepted]
PHST- 2020/12/15 06:00 [pubmed]
PHST- 2021/07/20 06:00 [medline]
PHST- 2020/12/14 11:17 [entrez]
PHST- 2020/12/12 00:00 [pmc-release]
AID - CAM43655 [pii]
AID - 10.1002/cam4.3655 [doi]
PST - ppublish
SO  - Cancer Med. 2021 Feb;10(3):806-823. doi: 10.1002/cam4.3655. Epub 2020 Dec 12.