The prognostic significance of a novel ferroptosis-related gene model in breast cancer

Abstract

Background: Breast cancer (BRCA) is the most common malignancy with high heterogeneity in women, and the prognostic prediction for BRCA has remained poor. Ferroptosis, a recently identified iron-dependent form of programmed cell death, plays a significant role in BRCA treatment. Some BRCA cell lines are proven to be sensitive to ferroptosis, and some ferroptosis-related genes have been identified as divers or suppressors in the progress of BRCA. This study aimed to explore the prognostic value of ferroptosis-related genes in BRCA.Methods: A ferroptosis-related gene list, messenger RNA (mRNA) gene expression of BRCA patients, and corresponding clinicopathological data were collected from public databases. The patients of the Cancer Genome Atlas (TCGA) were identified as the training cohort, and the ones of the Gene Expression Omnibus (GEO) were looked as the validation cohort. Univariate Cox regression analysis was utilized to identify prognostic ferroptosis-related genes, and subsequent multivariate analysis further screened out important genes to establish a prognostic model. Receiver operating characteristic (ROC) curves were used to validate the model in both internal and external cohorts. Functional analysis was generated to evaluate the potential correlation between tumor immunity and ferroptosis-related genes in BRCA.Results: A ferroptosis-related gene signature stratifying patients into 2 risk score groups was established based on the TCGA cohort, and validated in the GEO cohort. Patients with lower risk scores had better overall survival (OS) compared to those with higher risk scores (P<0.001, TCGA cohort; P<0.05, GEO cohort). The risk score was independently associated with the OS of BRCA patients (P<0.001, TCGA cohort; P<0.05, GEO cohort). The area under the curves (AUCs) of the model in the training and validation cohorts were all around 0.7. Immune-related biological pathways and immune status were significantly different between the 2 divided risk groups. Conclusions:The novel prognostic model composed of 9 ferroptosis-related genes accurately predicts the survival of BRCA patients. It might provide a new sight for ferroptosis-related BRCA therapy.

The cuproptosis-related signature predicts prognosis and indicates immune microenvironment in breast cancer

“…To further explore the predictive ability of our signature, a comparison was performed among several significant molecular signatures employed for predicting OS in patients with BC. Compared with the other signature, such as ferroptosis, necroptosis, pyroptosis, and immune-related ( Lin et al, 2020 ; Zhong et al, 2020 ; Wang et al, 2021a ; Wu et al, 2021a ; Zhu et al, 2021b ; Ding et al, 2021 ; Ye et al, 2021 ; Lu et al, 2022a ; Lu et al, 2022b ; Chen et al, 2022 ; Chu et al, 2022 ; Yu et al, 2022 ; Zou et al, 2022 ), our signature indicated much higher AUCs, which indicated a better predictive ability, especially in predicting the long-term survival status. Furthermore, we constructed a prognostic nomogram that could simplify treatment decision-making for patients with BC.…”

“…In our study, the AUCs of the signatures at 3-, 5-, and 10-year were 0.683, 0.640, and 0.794, respectively, significantly higher than most hallmark predictive models. Table 1 showed that the 3-, 5-, and 10-year AUCs of the other four prognostic signatures, namely, the 9 ferroptosis-related gene signature (3-, 5-, and 10-year AUCs: 0.713, 0.713, and 0.684) ( Lu et al, 2022a ), 4 immune-related gene signature (3-, 5-, and 10-year AUCs: 0.692, 0.691, and 0.715) ( Ding et al, 2021 ), 7 pyroptosis-related gene signature (3-, 5-, and 10-year AUCs: 0.785, 0.769, and 0.711) ( Chu et al, 2022 ), and 6 autophagy-related gene signature (3-, 5-, and 10-year AUCs: 0.640, 0.600, and 0.610) ( Zhong et al, 2020 ) were comparable to the predictive capabilities of our predictive model, and our signature stand out with a clear advantage in predicting the long-term survival of BC patients, with a 10-year AUC of 0.819. We also listed the other signatures that focus more on short-term survival, such as 1-year, 2-year, 3-year, and 5-year survival.…”

A ferroptosis-related gene signature for overall survival prediction and immune infiltration in lung squamous cell carcinoma

“…The ferroptosis-related gene signature has been successfully constructed to predict the prognosis in patients with hepatocellular carcinoma [ 56 ], breast cancer [ 57 ], pancreatic adenocarcinoma [ 58 ], and cholangiocarcinoma [ 59 ]. Additionally, in LUAD, a ferroptosis-related gene signature including five genes was constructed to predict prognosis [ 60 ].…”

Identification of CISD1 as a Prognostic Biomarker for Breast Cancer

“… 5 Studies have shown that some ferroptosis-related genes have been identified as suppressor genes in the process of BRCA. 6 , 7 …”

“…5 Studies have shown that some ferroptosisrelated genes have been identified as suppressor genes in the process of BRCA. 6,7 CISD1 is a protein containing the CDGSH iron-sulfur domain, which is located in the outer membrane of mitochondria and is known to negatively regulate ferroptosis. 8 While studies have found that CISD1 plays an important role in promoting tumorigenesis and tumor progression in many cancer types, 9 recent studies also suggest that CISD1 can be used as a biomarker and target for breast cancer.…”