A Novel Ferroptosis-Related Gene Signature For Clinically Predicting Recurrence After Hepatectomy of Hepatocellular Carcinoma Patients.

Abstract

Background: The high HCC recurrence rate was the main reason for the poor prognosis after hepatectomy. In this present study, we identified a novel ferroptosis-related gene signature for clinically predicting HCC recurrence after hepatectomy.Methods: Ferroptosis-related genes were obtained from the FerrDb database. We identified the ferroptosis-related differentially expressed genes (FDEGs) between HCC tissues and normal tissues from the GSE14520 dataset. These FDEGs were used to perform a univariate and multivariate regression analysis to construct HCC recurrence models. An independent HCC cohort from TCGA database was used to validate the reliability of the multi-gene HCC recurrence model. The predictive nomogram and DCA was built to estimate the recurrence predicting capacity of the multi-gene signature. GO, KEGG and GSEA were used to further investigate the potential mechanism of these FDEGs.Results: A total of 39 FDEGs were identified. A seven-gene signature (MAPK9, SLC1A4, PCK2, ACSL3, STMN1, CDO1, and CXCL2) was constructed for HCC recurrence prediction. Patients in high-risk groups exhibited a significantly poor prognosis compared with low-risk patients in both the training set (GSE14520 cohort) and the validation set (TCGA cohort). Multivariate cox regression analysis demonstrated that the 7-gene signature were independent risk factors for RFS in HCC patients. The nomograms incorporating 7-gene signature and clinical prognostic risk factors were able to effectively predict RFS. KEGG analysis showed that FDEGs were mainly enriched in Ferroptosis, Hepatocellular carcinoma pathway, MAPK signaling pathway, and so on. GSEA analysis revealed that the high-risk group was enriched with multiple oncology characteristics and invasive-related pathways.Conclusion: Our study constructed a seven ferroptosis-related gene signature and established a prognostic nomogram for clinically predicting recurrence after hepatectomy and offered novel research directions for personalized treatment in HCC patients.

A novel oxidative stress- and ferroptosis-related gene prognostic signature for distinguishing cold and hot tumors in colorectal cancer

“…It was also reported that the effects of nanomedicine in targeting ferroptosis and apoptosis can be enhanced by oxidative stress (26). In recent years, some studies focused on constructing oxidative stress or ferroptosis-related risk models for predicting patient survival and immune landscapes in various types of malignant tumors (27)(28)(29)(30)(31). However, few risk models were developed based on a combination of these two phenotypes.…”

Identification of a novel ferroptosis-related gene signature associated with prognosis, the immune landscape, and biomarkers for immunotherapy in ovarian cancer

“…Meanwhile, prognostic analysis suggested that higher PTGS2 expression may be associated with poor OS in OV, but the results of different studies were somewhat conflicting ( Steffensen et al, 2007 ). Moreover, SLC1A4, PCK2 and XBP1 were upregulated by 2-fold in erastin-treated HT-1080 cells ( Dixon et al, 2014 ) and could be used as powerful prognostic markers in hepatobiliary cancer ( Liu et al, 2020 ; Peng et al, 2021 ; Wang et al, 2022 ). As the key genes of ferroptosis, SLC3A2, MT1G and ACSL3 have also been widely explored in multiple FRG prognostic models.…”

Ferroptosis and cuproptosis prognostic signature for prediction of prognosis, immunotherapy and drug sensitivity in hepatocellular carcinoma: development and validation based on TCGA and ICGC databases

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