Screening of ferroptosis-related genes with prognostic effect in colorectal cancer by bioinformatic analysis

Abstract

Colorectal cancer (CRC) remains a common malignant tumor of digestive tract with high incidence rate and high mortality in the worldwide. The current clinical treatments of CRC often fail to achieve satisfactory results. Searching for more effective prediction or prognosis biomarkers, or developing more targeted therapeutic schedule may help to improve the outcomes of CRC patients. Here, we tried to study the effect of ferroptosis-related genes on CRC prognosis and make it clearer that ferroptosis has connection with immune environment. First, we obtained gene expression data of CRC and normal tissues, as well as corresponding clinical data from the Gene Expression Omnibus (GEO) database and the Cancer Genome Atlas (TCGA) database. The differentially expressed genes (DEGs) were intersected with ferroptosis-related gene set downloaded from FerrDb database, and 93 abnormally expressed ferroptosis-related genes were obtained. Then, these genes were analyzed for functional enrichment. Univariate Cox regression and multivariate Cox regression analyses were performed to establish prognostic model based on ferroptosis-related genes. In the process of exploring the correlation between prognostic genes and immune infiltration, we found that these genes were closely related to B cells, CD8+ T cells, CD4+ T cells, macrophages and other cells in CRC. In addition, we found a large proportion of plasma cells and macrophages in TCGA-COADREAD. Finally, a prognostic nomogram of ferroptosis-related genes was established, including age, sex, grade and other predicted values. To summary, we established a prognostic model of colorectal cancer (CRC) based on ferroptosis-related genes and further explored the relationship between these genes with immune microenvironment.

Molecular characteristics, clinical significance, and immune landscape of extracellular matrix remodeling-associated genes in colorectal cancer

“…The AUC values of the model predicting patients’ OS at 1, 3, and 5 years were 0.64 (95% CI = 0.71-0.57), 0.61 (95% CI = 0.66-0.56), and 0.60 (95% CI = 0.65-0.55), respectively ( Figure 5F ). Compared with other existing prognostic models for CRC, such as the ferroptosis-related genes prognostic model (AUC = 0.64, 0.64, 0.71 for 1,3,5-year OS, respectively) ( 23 ), the platelet-related prognostic model (AUC = 0.722, 0.706, 0.689 for 1,3,5-year OS,respectively) ( 24 ), and the anoikis and immune-related genes prognostic model (AUC = 0.671, 0.634, 0.638 for 1,3,5-year OS,respectively) ( 25 ), our model also demonstrated good predictive performance. With the increase of EAG_Score, the OS of patients decreased and the mortality rate gradually increased ( Figures 5G, H ).…”

Characterization of butyrate-metabolism in colorectal cancer to guide clinical treatment

“…AUC value of the risk model was 0.739, 0.753 and 0.727 for 1-, 3- and 5-year respectively, exhibiting superior performance than some other signatures in predicting the prognosis of CRC. In previous studies, ferroptosis-related gene signature was constructed in CRC, and AUC was 0.64, 0.64, and 0.71 for 1-, 3- and 5-year respectively 32 . A necroptosis-related risk score model was also identified, and AUC was 0.665, 0.712, and 0.758 for the 1-, 3-, and 5-year OS 33 .…”

Analysis of the correlation between non-alcoholic fatty liver disease and the risk of colorectal neoplasms

“…With the help of this gene set, a dual positive effects or a less negative effect could be achieved in the treatment of these patients. Third, FRGs have prognostic value in CRC ( Hu et al, 2022 ). According to our results, an inner correlation between FRG in NAFLD and those in CRC exists.…”