FECH Expression Correlates with the Prognosis and Tumor Immune Microenvironment in Clear Cell Renal Cell Carcinoma

Abstract

Background. Clear cell renal cell carcinoma (ccRCC) is, by far, the most prevalent and fatal kind of kidney cancer. Ferrochelatase (FECH) is an enzyme that performs a significant function in the onset and progression of many distinct kinds of malignant tumors. Nevertheless, its predictive usefulness in renal clear cell carcinoma (RCC) has not yet been fully investigated. Methods. FECH expression in ccRCC and healthy adjoining tissues was primarily screened utilizing data sourced from The Cancer Genome Atlas (TCGA) and subsequently validated using data from an independent cohort derived from the Gene Expression Omnibus (GEO) and the Human Protein Atlas HPA databases. The relationship among FECH expression, clinicopathological parameters, and overall survival (OS) was assessed utilizing multivariate analysis and Kaplan–Meier survival curves. Additionally, the protein networks with FECH interaction were constructed with the aid of the online Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). Gene ontology (GO) analysis, and gene set enrichment analysis (GSEA) were conducted based on TCGA data, and a single-sample GSEA was utilized to explore the link between FECH expression and the infiltration status of immune cells in the tumor. The Gene Expression Profiling Interactive Analysis (GEPIA) and TIMER databases were utilized to investigate the relationships of FECH expression with the infiltrating immune cells and the matching gene marker sets. Results. FECH expression was shown to be substantially lowered in ccRCC tumors as opposed to that observed in normal tissues ( p < 0.05 ). Lower levels of FECH expression were shown to have a strong association with higher grades of cancer and more advanced TNM stages. The findings of multivariate and univariate analyses illustrated that the OS in patients with ccRCC with low FECH expression is shorter in contrast with that in the high FECH expression group ( p < 0.05 ). It was discovered that CPOX and frataxin are key proteins that interact with FECH. ccRCC with FECH deficiency was linked to the lack of infiltrating immune cells and their respective marker sets, which included CD4+ T cells. Conclusion. In ccRCC, decreased FECH expression was linked to disease progression, unfavorable prognosis, and impaired immune cell infiltration.

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“…Cells with high rates of metabolic activity, such as cancer cells, inflammatory cells, and bacteria have lower amounts of ferrochelatase (FECH) , an enzyme capable of metabolizing PpIX, so the production of photoactive porphyrins is more pronounced than in healthy cells [ 25 ]. Reduced FECH expression is present in various tumors such as kidney [ 26 ], bladder [ 27 ], and colorectal [ 28 ]. Low FECH activity of cancer cells causes accumulation of PpIX and other porphyrins in tumors, while normal or high FECH activity results in low accumulation of PpIX in tissues [ 29 ].…”