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The interplay between autophagy and ferroptosis has been highlighted as an important event to decide cancer cell fate. However, the underlying mechanisms remain largely unclear. In this study, we systematically explored the expression, prognostic value and functional roles of lncRNA in autophagy and ferroptosis. By a set of bioinformatics analyses, we identified 363 autophagy- and ferroptosis-related lncRNAs (AF-lncRNAs) and found 17 of them are dramatically related to the prognosis of head and neck squamous cell carcinoma (HNSC) patients, named as prognosis-related AF-lncRNAs (PAF-lncRNAs). Based on six key PAF-lncRNAs, a risk score model was developed and used to categorize the TCGA-retrieved HNSC patients into two groups (high-risk vs. low-risk). Functional analysis showed the differentially expressed genes (DEGs) between the two groups were mainly enriched in immune-related pathways and regulated by a PAF-lncRNA-directed ceRNA (competitive endogenous RNA) network. Combined with a variety of immune infiltration analyses, we also found a decreased landscape of immune cell infiltration in high-risk groups. Together, by revealing PAF-lncRNAs with tumor prognostic features functioned through immune-related pathways, our work would contribute to show the pathogenesis of a lncRNA-directed interplay among autophagy, ferroptosis and tumor immunity in HNSC and to develop potential prognostic biomarkers and targets for tumor immunotherapy.

Identification of Autophagy- and Ferroptosis-Related lncRNAs Functioned through Immune-Related Pathways in Head and Neck Squamous Carcinoma