Assessment of Diagnosis, Prognosis and Immune Infiltration Response to the Expression of the Ferroptosis-Related Molecule HAMP in Clear Cell Renal Cell Carcinoma

Abstract

Background. Hepcidin antimicrobial peptide (HAMP) is a key factor in maintaining iron metabolism, which may induce ferroptosis when upregulated. However, its prognostic value and relation to immune infiltrating cells remains unclear. Methods. This study analyzed the expression levels of HAMP in the Oncomine, Timer and Ualcan databases, and examined its prognostic potential in KIRC with R programming. The Timer and GEPIA databases were used to estimate the correlations between HAMP and immune infiltration and the markers of immune cells. The intersection genes and the co-expression PPI network were constructed via STRING, R programming and GeneMANIA, and the hub genes were selected with Cytoscape. In addition, we analyzed the gene set enrichment and GO/KEGG pathways by GSEA. Results. Our study revealed higher HAMP expression levels in tumor tissues including KIRC, which were related to poor prognosis in terms of OS, DSS and PFI. The expression of HAMP was positively related to the immune infiltration level of macrophages, Tregs, etc., corresponding with the immune biomarkers. Based on the intersection genes, we constructed the PPI network and used the 10 top hub genes. Further, we performed a pathway enrichment analysis of the gene sets, including Huntington’s disease, the JAK-STAT signaling pathway, ammonium ion metabolic process, and so on. Conclusion. In summary, our study gave an insight into the potential prognosis of HAMP, which may act as a diagnostic biomarker and therapeutic target related to immune infiltration in KIRC.

High Hepcidin Levels Promote Abnormal Iron Metabolism and Ferroptosis in Chronic Atrophic Gastritis

“…The immune function of macrophages is influenced by their ability to regulate cellular iron homeostasis [ 47 ], and M1 macrophages have a high ferritin content and are susceptible to iron deposition [ 48 ]. The hepcidin level is related to the immune infiltration level of macrophages, positively correlating with the M1 type and negatively correlating with the M2 type [ 49 ]. A study demonstrated that activated hepcidin led to iron overload in macrophages within plaques, resulting in cellular cholesterol imbalance and the formation of foam cells [ 50 ].…”

TRP Gene Family as a Prognostic Marker for Kidney Renal Clear Cell Carcinoma: Analysis of TCGA Data

“…Even though surgical resection remains the primary method of therapy for restricted KIRC, some patients could still have distant metastases after surgery. Additionally, some patients failed to respond to radiation and chemotherapy, so their treatment outcomes and prognosis are quite unsatisfactory, leading to the 5-year relative survival rate of advanced KIRC less than 10% [8][9][10] . It is essential to avoid underestimating the potential future costs of kidney cancer to the global health system and the economy.…”