Screening and identification of immune-related genes for immunotherapy and prognostic assessment in colorectal cancer patients

Abstract

Background Increasing evidence indicates that the immune microenvironment plays a key role in the genesis and progression of colorectal cancer (CRC). This study aimed to establish an immune-related gene (IRG) signature and determine its clinical prognostic value in patients with CRC. Methods The RNA sequencing and associated clinical data of CRC were downloaded from The Cancer Genome Atlas (TCGA) database. We then screened for differentially expressed IRGs by intersecting with IRGs obtained from the Immunology Database and Analysis Portal. Functional enrichment analyses were carried out to determine the potential biological functions and pathways of the IRGs. We also explored the specific molecular mechanisms of the IRGs by constructing regulatory networks. Prognostic IRGs were obtained by LASSO regression analysis, and subsequently, gene models were constructed in the TCGA dataset to confirm the predictive capacity of these IRGs. Finally, we used the TIMER tool to assess the immune properties of prognostic IRGs and correlate them with immune cells. Results We identified 409 differentially expressed IRGs in patients with CRC. Kyoto Encyclopaedia of Genes and Genomes and Gene Ontology enrichment analyses suggested that these differentially expressed IRGs were significantly related to 102 cancer signalling pathways and various biological functions. Based on the prediction and interaction results, we obtained 59 TF–IRG, 48 miRNA–IRG, and 214 drug–IRG interaction networks for CRC. Four prognostic genes (POMC, TNFRSF19, FGF2, and SCG2) were developed by integrating 47 survival-related IRGs and 42 characteristic CRC genes. The results of gene model showed that patients in the low risk group had better survival outcomes compared to those in the high risk group. The expression of POMC, TNFRSF19, FGF2, and SCG2 was significantly correlated with immune cells. Conclusion This study identified some valid IRGs, and these findings can provide strong evidence for precision immunotherapy in patients with CRC.

Sympathetic nerve infiltration promotes stomach adenocarcinoma progression via norepinephrine/β2-adrenoceptor/YKL-40 signaling pathway

“…We used UALCAN, an interactive web resource ( http://ualcan.path.uab.edu/index.html ) which provides cancer OMICS data, including TCGA (The Cancer Genome Atlas) [ 22 ] and MET500 database [ 23 ], to screen the top 50 overexpressed genes and to analyze the expression of YKL-40 (CHI3L1) in STAD patients. TIMER (Tumor Immune Estimation Resource) [ 24 ] ( https://cistrome.shinyapps.io/timer ) provides survival module between gene expression and clinical outcome in a multivariable Cox proportional hazard model, and has the functions to draw Spearman's correlation curves and to provide pair-wise gene expression correlation analysis for given sets of TCGA and/or GTEx (the Genotype-Tissue Expression) database [ 25 ]. Using TIMER, we performed the correlation analysis between ADRB genes (ADRB1, ADRB2, and ADRB3) and CHI3L1, and analyzed the correlations of NGF expression and macrophage infiltration with the cumulative survival rate.…”

Constructing a prognostic model for colon cancer: insights from immunity-related genes

“…Typically, the immune system serves as a defense mechanism against neoplasia development. However, mounting evidence suggests that immune cell [5,6] infiltration is closely associated with the prognosis of CC patients. Specifically, the presence of cytotoxic CD8 + T cells within the central or peripheral regions of the tumor is indicative of a reduced risk of recurrence in patients with CC [7].…”