CCR4 is a prognostic biomarker and correlated with immune infiltrates in head and neck squamous cell carcinoma.

BACKGROUND

Increased evidence has indicated that the tumour microenvironment plays an essential in the development, treatment and prognosis of head and neck squamous cell carcinoma (HNSC). Recent studies have indicated CC chemokine receptor 4 (CCR4) plays an essential role in tumor invasion and other adverse biological behavior. This study used data from the Cancer Genome Atlas (TCGA) database to explore the role of in HNSC and its clinical significance.

METHODS

The gene expression and clinical data of HNSC patients in the TCGA database were extracted. Gene Expression Profiling Interactive Analysis (GEPIA) was used to analyze the expression of in tumor and non-tumor tissue. Kaplan-Meier survival analysis was used to analyze the relationship between expression and overall survival rate (OS), disease-specific survival (DSS), and progression-free interval (PFI) in HNSC. A logistic regression model was used to analyze the relationships between various clinical factors and expression. Gene Set Enrichment Analysis (GSEA) was used to explore the potential role of in HNSC. Additionally, we explored the relationship between and immune infiltration.

RESULTS

The expression of CCR4 in HNSC was not significantly different from that in normal tissue. The expression level of CCR4 in wild-type TP53 was higher than that in mutant TP53. Cox regression analysis showed the expression level of CCR4 was related to the patient's tumor grade and Tumor-Node-Metastasis (TNM) stage. CCR4 expression level is an independent prognostic factor. CCR4 is positively correlated with immune infiltration and immune checkpoints expression levels. The results of GSEA revealed that the high CCR4 expression group genes were enriched in allograft rejection, inflammatory response, IL-6/JAK/STAT3 signaling, interferon gamma response, and KRAS signaling up. Low CCR4 expression group genes were enriched in oxidative phosphorylation, MYC targets v1, DNA repair, reactive oxygen species pathway, and P53 pathway. Further, our study indicated CCR4 can also predict the prognosis of radiotherapy patients.

CONCLUSIONS

Our study found that was a prognostic marker related to HNSC immune infiltration, and patients with high expression of had a better prognosis.