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

Yijian Zhang; Kai Chen; Li Li; Weidong Mao; Dong Shen; Ninghua Yao; Lei Zhang

doi:10.21037/atm-21-3936

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

Ann Transl Med. 2021 Sep;9(18):1443. doi: 10.21037/atm-21-3936.

Authors

Yijian Zhang¹, Kai Chen², Li Li³, Weidong Mao⁴, Dong Shen⁴, Ninghua Yao⁵, Lei Zhang¹

Affiliations

¹ Department of Otolaryngology-Head and Neck Surgery, Affiliated Hospital of Jiangnan University, Wuxi, China.
² Department of Radiotherapy, First People's Hospital of Yancheng, Yancheng, China.
³ Department of Oncology, Huaian Hospital, Huai'an, China.
⁴ Department of Oncology, Jiangyin People's Hospital, Wuxi, China.
⁵ Department of Oncology, Affiliated Hospital of Nantong University, Nantong, China.

Abstract

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 CCR4 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 CCR4 in tumor and non-tumor tissue. Kaplan-Meier survival analysis was used to analyze the relationship between CCR4 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 CCR4 expression. Gene Set Enrichment Analysis (GSEA) was used to explore the potential role of CCR4 in HNSC. Additionally, we explored the relationship between CCR4 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 CCR4 was a prognostic marker related to HNSC immune infiltration, and patients with high expression of CCR4 had a better prognosis.

Keywords: CC chemokine receptor 4 (CCR4); biomarker; head and neck squamous cell carcinoma (HNSC); immune infiltrates.