Prognostic implications of ferroptosis-associated gene signature in colon adenocarcinoma

Abstract

BACKGROUND Colon adenocarcinoma (COAD) is one of the most common and fatal malignant tumors, which increases the difficulty of prognostic predictions. Thus, new biomarkers for the diagnosis and prognosis of COAD should be explored. Ferroptosis is a recently identified programmed cell death process that has the characteristics of iron-dependent lipid peroxide accumulation. However, the predictive value of ferroptosis-related genes (FRGs) for COAD still needs to be further clarified. AIM To identify some critical FRGs and construct a COAD patient prognostic signature for clinical utilization. METHODS The Cancer Genome Atlas database (TCGA) and Gene Expression Omnibus databases were the data sources for mRNA expression and corresponding COAD patient clinical information. Differentially expressed FRGs were recognized using R and Perl software. We constructed a multi-FRG signature of the TCGA-COAD cohort by performing a univariate Cox regression and least absolute shrinkage and selection operator Cox regression analysis. COAD patients from the Gene Expression Omnibus cohort were utilized for verification. RESULTS Our research showed that most of the FRGs (85%) were differentially expressed between the corresponding adjacent normal tissues and cancer tissues in the TCGA-COAD cohort. Seven FRGs were related to overall survival (OS) in the univariate Cox analysis (all P < 0.05). A model with five FRGs ( AKR1C1, AKR1C3, ALOX12, CRYAB, and FDFT1 ) was constructed to divide patients into high- and low-risk groups. The OS of patients in the high-risk group was significantly lower than that of the low-risk group (all P < 0.01 in the TCGA and Gene Expression Omnibus cohorts). The risk score was an independent prognosticator of OS in the multivariate Cox analysis (hazard ratio > 1, P < 0.01). The predictive capacity of the model was verified by a receiver operating characteristic curve analysis. In addition, a nomogram based on the expression of five hub FRGs and risk score can precisely predict the OS of individual COAD cancer patients. Immune correlation analysis and functional enrichment analysis results revealed that immunology-related pathways were abundant, and the immune states of the high-risk group and the low-risk group were different. CONCLUSION In conclusion, a novel five FRG model can be utilized for predicting prognosis in COAD. Targeting ferroptosis may be a treatment option for COAD.

AKR1C1 overexpression leads to lenvatinib resistance in hepatocellular carcinoma

“…Studies have revealed that AKR1C1 is linked to numerous ferroptosis-associated cancers, such as glioblastoma ( 26 ), colon adenocarcinoma ( 27 ), non-small cell lung cancer ( 28 ), breast cancer ( 29 ) and clear cell renal cell carcinoma ( 30 ). Recent research has indicated that sorafenib can elicit ferroptosis, a type of programmed cell death characterized by iron-dependent lipid peroxide accumulation ( 31 , 32 ).…”

AKR1C1 overexpression leads to lenvatinib resistance in hepatocellular carcinoma

“…Studies have revealed that AKR1C1 is linked to numerous ferroptosis-associated cancers, such as glioblastoma (26), colon adenocarcinoma (27), non-small cell lung cancer (28), breast cancer (29) and clear cell renal cell carcinoma (30). Recent research has indicated that sorafenib can elicit ferroptosis, a type of programmed cell death characterized by iron-dependent lipid peroxide accumulation (31,32).…”