Abstract
The heterogeneity and complexity of tumor-immune microenvironments lead to diverse immunotherapy effects among colon cancer patients. It is crucial to identify immune microenvironment-related biomarkers and construct prognostic risk models. In this study, the immune and stromal scores of 415 cases from TCGA were calculated using the ESTIMATE algorithm. AXIN2, CCL22, CLEC10A, CRIP2, RUNX3, and TRPM5 were screened and established a prognostic immune-related gene (IRG) signature using by univariate, LASSO, and multivariate Cox regression models. The predicted performance of IRG signature was external validated by GSE39582 (n=519). Stratified survival analysis showed IRG signature was an effective predictor of survival in patients with different clinical characteristics. The protein expression level of six genes was validated by immunohistochemistry analysis. Difference analysis indicated the mutation rate, immune cell of resting NK cells and regulatory T cells infiltration and four immune checkpoints of PD-1, PD-L1, LAG3 and VSIR expression levels in the high-risk group were significantly higher than those in the low-risk group. A nomogram incorporating the gene signatures and clinical factors was demonstrated had a good accuracy (1-, 3-, and 5-year AUC= 0.799, 0.791, 0.738). Our study identified a novel IRG signature, which may provide some references for the clinical precision immunotherapy of patients.
Keywords:
colon cancer; immune checkpoints; immune-related genes; prognostic model; tumor mutation burden.
Publication types
-
Research Support, Non-U.S. Gov't
-
Validation Study
MeSH terms
-
Adaptor Proteins, Signal Transducing / genetics
-
Adaptor Proteins, Signal Transducing / immunology
-
Adenocarcinoma / genetics*
-
Adenocarcinoma / immunology
-
Adenocarcinoma / mortality
-
Adenocarcinoma / pathology
-
Aged
-
Antigens, CD / genetics
-
Antigens, CD / immunology
-
Axin Protein / genetics
-
Axin Protein / immunology
-
B7 Antigens / genetics
-
B7 Antigens / immunology
-
B7-H1 Antigen / genetics
-
B7-H1 Antigen / immunology
-
Chemokine CCL22 / genetics
-
Chemokine CCL22 / immunology
-
Colonic Neoplasms / genetics*
-
Colonic Neoplasms / immunology
-
Colonic Neoplasms / mortality
-
Colonic Neoplasms / pathology
-
Core Binding Factor Alpha 3 Subunit / genetics
-
Core Binding Factor Alpha 3 Subunit / immunology
-
Databases, Genetic
-
Female
-
Humans
-
Killer Cells, Natural
-
LIM Domain Proteins / genetics
-
LIM Domain Proteins / immunology
-
Lectins, C-Type / genetics
-
Lectins, C-Type / immunology
-
Lymphocyte Activation Gene 3 Protein
-
Lymphocytes, Tumor-Infiltrating
-
Male
-
Middle Aged
-
Multivariate Analysis
-
Nomograms
-
Prognosis
-
Programmed Cell Death 1 Receptor / genetics
-
Programmed Cell Death 1 Receptor / immunology
-
Proportional Hazards Models
-
Survival Rate
-
T-Lymphocytes, Regulatory
-
TRPM Cation Channels / genetics
-
TRPM Cation Channels / immunology
-
Transcriptome*
-
Tumor Microenvironment / genetics
-
Tumor Microenvironment / immunology
Substances
-
AXIN2 protein, human
-
Adaptor Proteins, Signal Transducing
-
Antigens, CD
-
Axin Protein
-
B7 Antigens
-
B7-H1 Antigen
-
CCL22 protein, human
-
CD274 protein, human
-
CLEC10A protein, human
-
CRIP2 protein, human
-
Chemokine CCL22
-
Core Binding Factor Alpha 3 Subunit
-
LIM Domain Proteins
-
Lectins, C-Type
-
PDCD1 protein, human
-
Programmed Cell Death 1 Receptor
-
Runx3 protein, human
-
TRPM Cation Channels
-
TRPM5 protein, human
-
VSIR protein, human
-
Lymphocyte Activation Gene 3 Protein
-
Lag3 protein, human