Identification of a Novel Necroptosis-related LncRNA Signature for Prognostic Prediction and Immune Response in Oral Squamous Cell Carcinoma

Background: Necroptosis is a caspase-independent regulated necrotic cell death modality that elicits strong adaptive immune responses, and has the potential to activate antitumor immunity. Long non-coding RNAs (lncRNAs) have critical effects on oral squamous cell carcinoma (OSCC), which are closely associated with the prognosis and immune regulation of OSCC patients.

Objective: This study aimed to identify a novel necroptosis-related lncRNAs signature to predict the prognosis and immune response of OSCC patients and provide patients with anti-tumor drug selection through bioinformatics analysis and in vitro experiments.

Methods: A series of analyses, including differential lncRNA screening, survival analysis, Cox regression analysis, ROC analysis, nomogram prediction, enrichment analysis, tumor-infiltrating immune cells, drug sensitivity analysis, and consensus cluster analysis, were performed to determine and validate the prognostic value of necroptosis-associated lncRNAs signature in OSCC. And real-time quantitative polymerase chain reaction (RT-qPCR) was used to determine the expression levels of these lncRNAs.

Results: This signature including 5 lncRNAs (AC099850.3, StarD4-AS1, AC011978.1, LINC01503, CDKN2A-DT) in OSCC associated with necroptosis were established and verified by bioinformatics. Further, ROC, K-M, univariate/multivariate Cox regression, and nomogram analysis were used to evaluate the model's features for OSCC prognosis. Using multiple bioinformatics techniques, the levels of tumor-infiltrating immune cells, immune checkpoints and semi-inhibitory concentrations showed significant differences across risk subtypes. By consensus cluster analysis, there were significant differences between clusters in survival, immune checkpoint expression, clinicopathological correlation, and tumor immunity. RT-qPCR showed that AC099850.3, AC011978.1, LINC01503 were up-regulated, STARD4-AS1 and CDKN2A-DT were down-regulated in OSCC cell lines compared with human normal oral keratinoid cell line.

Conclusion: We established 5-NRLs markers, which is useful for assessing OSCC immune response and prognosis, recommending personalized antitumor drugs. The expression level of 5-NRLs in OSCC was identified in vitro, and the results preliminarily verified this model. And this study would generate new insights for future experimental research.