New Biomarkers Identified for Predicting Prognosis in Laryngeal Cancer
Laryngeal cancer is a serious and aggressive cancer that occurs in the larynx, or voice box. Although it is not among the most common cancers, it carries a poor survival rate compared to many other cancers. Surgery remains a key treatment, but the risk of lymph node metastasis and recurrence is high. New biomarkers are urgently needed to improve early diagnosis, guide treatment, and predict patient outcomes more accurately.
The Importance of m6A Modification and Ferroptosis
Recent research has shown that RNA molecules can be chemically modified through a process called m6A methylation, which affects how genes are expressed and how cells behave. Another important process is ferroptosis, a form of cell death that depends on iron and oxidative stress. Both m6A modifications and ferroptosis are closely linked to cancer progression, including in laryngeal cancer. Understanding these connections opens up new possibilities for identifying key biomarkers and therapeutic targets.
What This Study Set Out to Do
Researchers used large public datasets, including TCGA-HNSC and GSE65858, to identify genes involved in both m6A regulation and ferroptosis that might predict prognosis in laryngeal cancer. They aimed to build a risk model that could classify patients into high- and low-risk groups and explore how these biomarkers might relate to the tumor’s immune environment and drug sensitivity.
How the Study Was Conducted
The scientists performed bioinformatics analyses to find differentially expressed genes linked to both m6A and ferroptosis. Using statistical methods like univariate Cox regression and LASSO regression, they narrowed down the candidates to three key genes: TFRC, RGS4, and FTH1. These genes were then used to construct a risk model, which was validated using independent datasets. Additional experiments, including qRT-PCR and western blotting, confirmed the expression of these genes in laryngeal cancer tissues and cell lines.
Key Findings
TFRC, RGS4, and FTH1 were found to be highly expressed in laryngeal cancer compared to normal tissues. Patients with higher expression of TFRC and FTH1 had worse survival outcomes, making them important prognostic markers. The risk model based on these three genes could accurately predict overall survival, and patients in the low-risk group had significantly better outcomes than those in the high-risk group.
Immune Microenvironment and Drug Sensitivity
The study showed that the high-risk group had a more immunosuppressive tumor environment, with higher stromal and immune scores. PD-L1 expression was significantly higher in the high-risk group, suggesting potential responsiveness to immune checkpoint therapies. Mutation analysis revealed different genetic mutation profiles between the high- and low-risk groups. Drug sensitivity analysis showed that patients in different risk groups responded differently to various chemotherapy agents, suggesting that the risk model could also help guide treatment selection.
Building a Predictive Tool
A nomogram was developed by combining the risk score with clinical factors like gender and tumor stage. This tool can predict a patient’s probability of surviving two, three, or four years after diagnosis, with strong accuracy as shown by calibration curves and ROC analysis.
Biological Insights from Pathway Analysis
Genes that differed between high- and low-risk groups were involved in important biological processes such as extracellular matrix remodeling and neuroactive ligand-receptor interactions. These pathways are known to influence tumor growth, immune escape, and metastasis, offering more potential targets for therapy.
Potential Applications in Diagnosis and Monitoring
The researchers proposed that TFRC, RGS4, and FTH1 could serve as biomarkers for early detection through methods like liquid biopsy or circulating tumor DNA analysis. Abnormal methylation patterns of these genes could also be used to monitor disease progression or response to therapy.
The study relied heavily on public datasets, which have variability. Experiments to directly test the roles of TFRC, RGS4, and FTH1 in laryngeal cancer progression and treatment resistance are still needed.
To learn more, check this out!: Identification of m6 A-regulated ferroptosis biomarkers for prognosis in laryngeal cancer | BMC Cancer | Full Text
