Abstract
Background: Head and neck squamous cell carcinoma (HNSCC) is a malignant tumor, which makes the prognosis prediction challenging. Ferroptosis is an iron-dependent form of non-apoptotic regulated cell death, which could affect cancer development. However, the prognostic value of ferroptosis-related long non-coding RNA (lncRNA) in HNSCC is still limited. Methods: In the current study, we employed the DESeq2 method to characterize the differentially expressed ferroptosis-related genes (FEGs) between cancer and normal samples. Next, the FEG-related lncRNAs (FElncRNAs) were identified using Spearman’s correlation analysis and multiple permutation hypotheses. Subsequently, LASSO and stepwise multivariate Cox regression analyses were undertaken to recognize the prognosis-related FElncRNA signature (PFLS) and risk scores. Results: Herein, we first identified 60 dysregulated FEGs and their co-expressed FElncRNAs in HNSCC. Then, we recognized a set of six FElncRNAs PFLS (SLCO4A1-AS1, C1RL-AS1, PCED1B-AS1, HOXB-AS3, MIR9-3HG, and SFTA1P) for predicting patients’ prognostic risks and survival outcomes. We also assessed the efficiency of PFLS in the test set and an external validation cohort. Further parsing of the tumor immune microenvironment showed the PFLS was closely associated with immune cell infiltration abundances. Notably, the low-risk group of the PFLS showed a higher MHC score and cytolytic activity (CYT) score than the high-risk group, implying the low-risk group may have greater tumor surveillance and killing ability. In addition, we observed that the expression levels of two immune checkpoints (ICPs), i.e., programmed cell death protein 1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1), showed significant associations with patients’ risk score, prompting the role of the PFLS in ICP blockade therapy. Finally, we also constructed a drug–PFLS network to reinforce the clinical utilities of the PFLS. Conclusion: In summary, our study indicated that FElncRNAs played an important role in HNSCC survival prediction. Identification of PFLS will contribute to the development of novel anticancer therapeutic strategies.
Highlights
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common type of malignant tumor among adults with a 5year survival rate of less than 70% (Pulte and Brenner, 2010; Johnson et al, 2020)
A total of 36 upregulated and 24 downregulated ferroptosis-related gene (FEG) were identified (Figures 1A,B, Supplementary Table S2). We annotated their biological functions and observed that these FEGs mainly participated in multiple metabolic processes and cancerrelated pathways (Figures 1C,D), such as cellular response to chemical stress (GO:0062197), reactive oxygen species metabolic process (GO:0072593), cellular response to oxidative stress (GO:0034599), microRNAs in cancer, and central carbon metabolism in cancer, etc
FERGs were associated with metabolic processes and might play an important role in HNSCC
Summary
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common type of malignant tumor among adults with a 5year survival rate of less than 70% (Pulte and Brenner, 2010; Johnson et al, 2020). HNSCC frequently appears in linings of the oral cavity, the pharynx, or the larynx (Tumino and Vicario, 2004). These tumors affect over 800,000 individuals worldwide (Johnson et al, 2020). Characterization of the ferroptosis-related lncRNA signature for improving survival prediction in HNSCC is still limited. Head and neck squamous cell carcinoma (HNSCC) is a malignant tumor, which makes the prognosis prediction challenging. The prognostic value of ferroptosis-related long non-coding RNA (lncRNA) in HNSCC is still limited
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