SLC39A7

Bladder cancer (BLCA) is one of the most prevalent cancers worldwide. Ferroptosis is a newly discovered form of non-apoptotic cell death that plays an important role in tumors. However, the prognostic value of ferroptosis-related genes (FRGs) in BLCA has not yet been well studied.

In this study, we performed consensus clustering based on FRGS and categorized BLCA patients into 2 clusters (C1 and C2). Immune cell infiltration score and immune score for each sample were computed using the CIBERSORT and ESTIMATE methods. Functional annotation of differentially expressed genes were performed by Gene Ontology (GO) and KEGG pathway enrichment analysis. Protein expression validation were confirmed in Human Protein Atlas. Gene expression validation were performed by qPCR in human bladder cancer cell lines lysis samples.

C2 had a significant survival advantage and higher immune infiltration levels than C1. Additionally, C2 showed substantially higher expression levels of immune checkpoint markers than C1. According to the Cox and LASSO regression analyses, a novel ferroptosis-related prognostic signature was developed to predict the prognosis of BLCA effectively. High-risk and low-risk groups were divided according to risk scores. Kaplan-Meier survival analyses showed that the high-risk group had a shorter overall survival than the low-risk group throughout the cohort. Furthermore, a nomogram combining risk score and clinical features was developed. Finally, SLC39A7 was identified as a potential target in bladder cancer.

In conclusion, we identified two ferroptosis-clusters with different prognoses using consensus clustering in BLCA. We also developed a ferroptosis-related prognostic signature and nomogram, which could indicate the outcome.

The tumor microenvironment (TME) significantly influences disease progression through immune infiltration, while ferroptosis, a recently discovered cell death mechanism, plays a crucial role in tumor suppression. However, its role in breast cancer is not clear. In this study, we analyzed bulk RNA and single-cell RNA sequencing data from 1217 samples, including 1104 breast cancer patients and 113 controls, to identify ferroptosis-related genes (FRGs) and construct a prognostic model. Using univariate cox regression, LASSO regression, and multivariate cox regression analysis, we discovered 21 FRGs and 3 TME-related immune cell types with prognostic value. Dimensionality reduction clustering and visualization were performed using the UMAP method, while the immune infiltration process was calculated with the TIP online tool. We employed GSEA enrichment analysis, WGCNA clustering analysis, and correlation analysis to examine functional differences, and the mutation analysis of the best and worst prognosis groups was conducted using the maftools package. Our findings revealed that knocking down the expression of the hub gene SLC39A7 significantly impacted cancer cell apoptosis and combining ferroptosis and TME scores yielded high prognostic power. Epithelial cells and B cells exhibited higher ferroptosis scores, which were independently associated with immune checkpoint blockade (ICB) response and ICB gene expression. This study provides a foundation for further exploration of the relationship between ferroptosis and ICB response in breast cancer. In conclusion, we developed a prognostic model based on ferroptosis and infiltrated immune cells that effectively stratified breast cancer patients and demonstrated the role of SLC39A7 in breast cancer pathogenesis through the regulation of apoptosis.

Systemic sclerosis (SSc) is a multisystem connective tissue disease. Skin fibrosis, the hallmark of this disease, is defined as the excess deposition and accumulation of extracellular matrix, mainly type 1 collagen, in the dermis. SLC39A7 is an intracellular zinc transporter that plays a unique role in connective tissue formation. Therefore, we investigated the expression and role of SLC39A7 in SSc. Using immunohistochemical staining we demonstrated the overexpression of SLC39A7 in the skin of SSc patients. Quantitative real-time PCR and western blot data analysis showed that both SLC39A7 mRNA and protein levels were significantly upregulated in dermal fibroblasts from SSc patients compared to healthy controls. We used the shRNA lentiviral particle transduction system to stably knockdown the expression of SLC39A7 in SSc fibroblasts. The results showed that knockdown of SLC39A7 suppressed the production of type 1 collagen. These findings provide evidence that SLC39A7 is involved in the pathogenesis of SSc and that SLC39A7 plays a positive role in its progression.