Identification and in vitro validation of prognostic lncRNA signature in head and neck squamous cell carcinoma

Long non-coding RNAs (lncRNAs) are promising cancer prognostic markers. However, the clinical significance of lncRNA signatures in evaluating overall survival (OS) outcomes of head and neck squamous cell carcinoma (HNSCC) has not been explored. This study aimed to assess the significance of lncRNA in HNSCC and to develop a lncRNA signature related to OS in HNSCC. LncRNA expression matrices were retrieved from the Cancer Genome Atlas (TCGA) data. Least Absolute Shrinkage and Selection of the Operator (LASSO), univariate and multivariate Cox regression were used for establishing a prognostic model. In vitro experiments were carried out to demonstrate the biological role of lncRNA. A prognosis model based on 7 DElncRNAs was finally established.The patients were then divided into high-risk and low-risk groups. Relative to the low-risk group, overall survival times for patients in the high-risk group were significantly low (P=2.466e-07). Risk score remained an independent prognostic factor in univariate (HR=1.329, 95%CI=1.239-1.425, p < 0.001) and multivariate (HR=1.279, 95%CI=1.184-1.382, p < 0.001) Cox regression analyses. The area under the curve (AUC) of the signature was as high as 0.78. Expressions of FOXD2-AS1 in tumor tissues were elevated, and significantly correlated with OS (P=0.008). FOXD2-AS1 silencing then significantly reduced HNSCC cell proliferation, invasion, and migration. In conclusion, a lncRNA signature was established for HNSCC prognostic prediction and FOXD2-AS1 was identified as an HNSCC oncogene.

Automated summary

This study established an lncRNA signature related to the overall survival outcomes of HNSCC patients, identifying FOXD2-AS1 as an oncogene in HNSCC. In vitro experiments demonstrated that FOXD2-AS1 plays a significant biological role in HNSCC cell proliferation, invasion, and migration.