Construction and Validation of a Ferroptosis-Related Prognostic Signature for Melanoma Based on Single-Cell RNA Sequencing

Abstract

Melanoma, the deadliest type of skin cancer, is on the rise globally. The generally poor prognosis makes melanoma still an enormous public health problem. Ferroptosis is a newly emerging form of iron-dependent regulated cell death, which has been implicated in the development and treatment of several tumors. However, whether there is a connection between ferroptosis-related genes and the prognosis of melanoma patients remains an enigma. In the present study, we identified a ferroptosis-related genes signature to predict the prognosis of melanoma patients by analyzing single-cell RNA-sequencing data from the Gene Expression Omnibus (GEO). Single-cell trajectory analysis was performed to explore malignant differentiation. CellChat was used to investigate intercellular communications in melanoma. Collectively, a novel four-gene signature (CP, MAP1LC3A, transferrin, and TP53) was constructed for prognosis prediction. COX proportional hazards regression analysis showed that the established ferroptosis-associated risk model was an independent prognostic predictor for melanoma patients (HR = 2.3293; 95%CI 1.1528–4.706) (p < 0.018). Patients with low-risk scores had significantly better overall survival (OS) than those with high-risk scores in The Cancer Genome Atlas, GSE59455, and GSE22153 dataset (p = 0.0015, p = 0.031, p = 0.077). Furthermore, the gene expression level of the four genes were verified in multistrain melanoma cell lines and normal human epidermal melanocytes (NHEM). The protein expression level of the four genes in clinical samples were further verified in the Human Protein Atlas (HPA) databases. Taken together, our study identified the prognostic significance of the ferroptosis-related genes in melanoma and developed a novel four-gene prognostic signature, which may shed light on the prognostic assessment and clinical decision making for melanoma patients.

Comprehensive Analysis of Cuproptosis-Related Genes in Immune Infiltration and Prognosis in Melanoma

“…Evaluation of the prognostic value of ferroptosis regulated genes has been widely conducted in diverse tumors, such as melanoma, clear cell renal cell carcinoma, breast cancer, lung adenocarcinoma, hepatocellular carcinoma, and so on ( Liang et al, 2020 ; Jin et al, 2021 ; Li et al, 2021 ; Wang et al, 2021 ; Ping et al, 2022 ). The correlation between ferroptosis regulators and immune signatures has also been explored in different tumors, including melanoma ( Fan et al, 2021 ; Wang et al, 2021 ; Liu et al, 2022 ). Dividing tumor patients into subgroups based on their molecular signatures, such as ferroptosis-related gene signatures, enable us to predict their diverse phenotypes, treatment response, and prognosis ( Wang et al, 2021 ).…”

Serum Iron Level and 10-Year Survival after Melanoma

“…There are studies exploring prognostic gene models related to ferroptosis in tumors. Liu et al identified the prognostic significance of ferroptosis-related genes (FRGs) in melanoma, and proposed a novel four-gene prognostic signature that may impact the assessment and clinical decision making for melanoma patients [ 23 ]. A recent study suggested a 10-biomarker signature that could be clinically used to predict the prognosis of cutaneous melanoma [ 24 ].…”

Ce6-modified Fe ions-doped carbon dots as multifunctional nanoplatform for ferroptosis and photodynamic synergistic therapy of melanoma

“…The concept of ferroptosis has provided innovative insights into the development of effective combination therapies and synergistic strategies for cancer treatments [ 10 – 12 ]. According to previous reports, melanoma is potentially more susceptible to ferroptosis than other tumors, which stems from the higher levels of dissociative iron in melanoma cells [ 13 ], revealing the bright prospect of ferroptosis in developing innovative strategies for melanoma therapy. Nevertheless, there is still a lack of stable and valid ferroptosis inducers, highlighting the need for further optimization of novel nanomaterials to activate ferroptosis.…”