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

Wenru Jiang; Yingtao Song; Zhaowei Zhong; Jili Gao; Xiaofei Meng

doi:10.3389/fgene.2021.785839

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

Front Genet. 2021 Dec 17:12:785839. doi: 10.3389/fgene.2021.785839. eCollection 2021.

Authors

Wenru Jiang¹, Yingtao Song¹, Zhaowei Zhong¹, Jili Gao¹, Xiaofei Meng²

Affiliations

¹ Department of Implant and Prosthodontics, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
² Donglai Road Stomatological Clinic, Laizhou, China.

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.

Keywords: head and neck squamous cell carcinoma; immune checkpoint blockade therapy; lncRNA; prognosis prediction; tumor immune microenvironment.