LINC01614 is a promising diagnostic and prognostic marker in HNSC linked to the tumor microenvironment and oncogenic function.

Abstract

Tumor initiation and metastasis influence tumor immune exclusion and immunosuppression. Long non-coding RNA (lncRNA) LINC01614 is associated with the prognosis and metastasis of several cancers. However, the relationship between LINC01614 and cancer immune infiltration and the biofunction of LINC01614 in head and neck squamous cell carcinoma (HNSC) remain unclear. The Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) datasets were used to analyze the expression difference and diagnostic value of LINC01614 in normal and tumor tissues. The correlation of pan-cancer prognosis and tumor stage of LINC01614 was analyzed based on the TCGA database. The pan-cancer association of LINC01614 expression with the tumor microenvironment (TME) including immune infiltration, expression of immune-related genes, and genomic instability parameters, was analyzed using the Spearman correlation method. The correlation between LINC01614 and tumor stemness evaluation indicators, RNA methylation-related genes, and drug resistance was also analyzed. The functional analysis of LINC01614 was performed using the clusterProfiler R package. The protein-protein interaction (PPI) network and ceRNA network of LINC01614 co-expressed genes and miRNA were constructed and visualized by STRING and Cytoscape, respectively. Finally, the cell location and influence of LINC01614 on cell proliferation and metastasis of HNSC cell lines were evaluated using FISH, CCK-8, wound-healing assay, and transwell assay. LINC01614 was found to be overexpressed in 23 cancers and showed a highly sensitive prediction value in nine cancers (AUC >0.85). LINC01614 dysregulation was associated with tumor stage in 12 cancers and significantly influenced the survival outcomes of 26 cancer types, with only Lymphoid Neoplasm Diffuse Large B-cell Lymphoma (DLBC), uterine corpus endometrial carcinoma (UCEC), and bladder urothelial carcinoma (BLCA) showing a benign influence. LINC01614 was also associated with immune cell infiltration, tumor heterogeneity, cancer stemness, RNA methylation modification, and drug resistance. The potential biological function of LINC01614 was verified in HNSC, and it was found to play important roles in proliferation, immune infiltration, immunotherapy response, and metastasis of HNSC. LINC01614 may serve as a cancer diagnosis and prognosis biomarker and an immunotherapy target for specific cancers.