Ferroptosis-Related Long Non-Coding RNA Signature Contributes to the Prediction of Prognosis Outcomes in Head and Neck Squamous Cell Carcinomas

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.

Cuproptosis-Related lncRNAs are Biomarkers of Prognosis and Immune Microenvironment in Head and Neck Squamous Cell Carcinoma

“…Studies have shown that lncRNA is abnormally expressed and regulated in a variety of tumors (Castro-Oropeza et al, 2018). It has been reported that abnormal lncRNAs can be used as prognostic indicators of various cancers (Ai et al, 2020;Gai et al, 2020;Jiang et al, 2021). At present, there are few studies on cuproptosis-related lncRNAs and their association with the prognosis of HNSC patients.…”

C10orf55, CASC2, and SFTA1P lncRNAs Are Potential Biomarkers to Assess Radiation Therapy Response in Head and Neck Cancers

“…In cell lines of non-small cell lung cancer, it is transcriptionally activated, which is responsible for the inhibition of cell proliferation or induction of apoptosis [ 48 ]. However, in 2020 and 2021, two studies were conducted, demonstrating its importance also in HNSCC [ 49 , 50 ]. SFTA1P has potential prognostic significance and can be used to assess survival outcomes [ 50 ].…”

More than a duologue: In-depth insights into epitranscriptomics and ferroptosis

“…On this groundwork, in tumoral and normal tissue-derived exosomes, their team discovered a distinctive expression level of miR-4443 between cisplatin-sensitive and cisplatin-resistant tissues and cell lines, and further functional and bioinformatics studies confirmed that m 6 A writer METTL3 was negatively regulated by miR-4443 overexpression to lower the m 6 A level on ferroptosis-suppressing protein 1 (FSP1), inhibiting its activity to suppress ferroptosis. Bioinformatics analyses on lncRNAs also revealed m 6 A regulators, namely, FMR1, HNRNPC, METTL16, METTL3, and METTL5, were expressed in higher levels than those in ferroptosis low-risk groups ( Jiang, W. et al, 2021a ). The aforementioned studies provided evidence that epitranscriptomics are phenomenally involved in ferroptotic disease models, particularly in drug-resistant cancers that have the characteristic to overcome cell death events.…”