CCR5 as a prognostic biomarker correlated with immune infiltrates in head and neck squamous cell carcinoma by bioinformatic study

• Published in: Hereditas Vol. 159; no. 1; pp. 1 - 37
• Main Authors: Li, Chunhong, Chen, Shanlin, Liu, Chuanyu, Mo, Chune, Gong, Weiwei, Hu, Jiahua, He, Min, Xie, Lei, Hou, Xianliang, Tang, Jianhong, Ou, Minglin
• Format: Journal Article
• Language: English
• Published: Lund BioMed Central 27-09-2022; BMC
• Subjects: Angiogenesis; Biomarkers; C-C chemokine receptor 5; Cancer therapies; CCR5 protein; CD4 antigen; Chemokine receptors; Chemokines; Datasets; Dendritic cells; Gene expression; Head & neck cancer; Head and neck carcinoma; Head and neck squamous cell carcinoma; Immune infiltration; Immunomodulation; Infiltration; Leukocytes (neutrophilic); Lymphatic system; Lymphocytes; Lymphocytes T; Macrophages; Medical prognosis; Metastases; Metastasis; Neutrophils; Pancreatic cancer; Patients; Prognosis; Prognostic biomarker; Squamous cell carcinoma; Survival analysis; Therapeutic targets; Tumor microenvironment; Tumor-infiltrating lymphocytes; Tumors
• ISSN: 1601-5223; 0018-0661; 1601-5223
• DOI: 10.1186/s41065-022-00251-y

Abstract
Background
C-C chemokine receptor 5 (CCR5) has recently been recognized as an underlying therapeutic target for various malignancies. However, the association of CCR5 with prognosis in the head and neck squamous cell carcinoma (HNSC) patients and tumor-infiltrating lymphocytes (TILs) is unclear.
Methods
In the current experiment, methods such as the Tumor Immune Estimation Resource Analysis (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, and Kaplan-Meier plotter Analysis were used to comprehensively evaluate the expression of CCR5 in human various malignancies and the clinical prognosis in HNSC patients. Subsequently, we used the TIMER database and the TISIDB platform to investigate the correlation between CCR5 expression levels and immune cell infiltration in the HNSC tumor microenvironment. Furthermore, immunomodulatory and chemokine profiling were performed using the TISIDB platform to analyse the correlation between CCR5 expression levels and immunomodulation in HNSC patients.
Results
We found that CCR5 expression in HNSC tumor tissues was significantly upregulated than in normal tissues. In HNSC, patients with high CCR5 expression levels had worse overall survival (OS, HR = 0.59,
p
 = 0.00015) and worse recurrence-free survival (RFS, HR = 3.27,
p
 = 0.00098). Upregulation of CCR5 expression is closely associated with immunomodulators, chemokines, and infiltrating levels of CD4+ T cells, neutrophils, macrophages, and myeloid dendritic cells. Furthermore, upregulated CCR5 was significantly associated with different immune markers in the immune cell subsets of HNSC.
Conclusions
High expression of CCR5 plays an important prognostic role in HNSC patients and may serve as a prognostic biomarker correlated with immune infiltration, and further studies are still needed to investigate therapeutic targeting HNSC patients in the future.