DKC1 as a Novel and Potential Prognostic Biomarker in Head and Neck Squamous Cell Carcinoma correlating With Immune Infiltrates

Abstract

Abstract Objective This study aims to investigate the association between DKC1 expression and prognosis in head and neck squamous cell carcinoma (HNSCC) Methods We obtained RNA-seq data for a cohort of patients with HNSCC from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases for the purpose of analysis. The expression levels of DKC1 were compared between HNSCC and paracancerous tissue to assess their differences. The Transwell invasion assay and flow cytometry were used to detect cellular invasion and apoptosis following the siRNA-mediated knockdown of DKC1 in HNSCC cell lines. Functional enrichment analysis was performed using the DAVID and KEGG databases to explore potential signaling pathways and associated biological functions. Gene set enrichment analysis of a single sample was performed using the ssGSEA algorithm to assess immune cell infiltration and predict sensitivity to immunotherapy. DKC1 methylation status was analyzed using the UALCAN and MethSurv databases. The tumor immune dysfunction and rejection (TIDE) framework was used to compare response rates to immunotherapy in low-versus high-risk patients based on their immune profiles and tumor characteristics. Kaplan-Meier survival curves and log-rank tests were used to compare the overall survival (OS) and disease-specific survival (DSS) of HNSCC patients with different levels of DKC1 expression. Cox proportional hazard regression analysis was performed to determine the independent prognostic value of DKC1. A nomogram was developed based on multivariate Cox regression analysis to predict the probability of OS at 1, 3, and 5 years after diagnosis, using age, M stage, Lymphovascular invasion, and DKC1 expression as predictors. Results Overexpression of DKC1 in HNSCC was meaningfully associated with T stage, pathologic grade, and survival time. DKC1 overexpression resulted in significantly decreased OS and DSS(disease-specific survival). The invasion and proliferative capacity of DKC1 knockdown cells were decreased by Transwell and flow cytometry. Single-factor Cox analysis confirmed DKC1 as an independent negative prognostic marker for OS. There is a close relationship between the hypomethylation status of DKC1 and a bad prognosis. The results of enrichment analysis reflected the NOD-like receptor/ interleukin-17 signaling pathway, drug resistance, leukocyte transepithelial migration, and neuroactive ligand-receptor interaction were enriched pathways. Overexpression of DKC1 was correlated with negative levels of CD8 + T cells, natural killer cells, effector memory T cells, and infiltration of macrophages. Using the TIDE framework, we found that patients with HNSCC in the high-risk group had considerably higher response rates to immunotherapy compared with those in the contrary group. Conclusion DKC1 could be a promising novel prognostic biomarker to predict HNSCC.