CCR7 Has Potential to Be a Prognosis Marker for Cervical Squamous Cell Carcinoma and an Index for Tumor Microenvironment Change

Abstract

The tumor microenvironment (TME) has an essential role in the development of cervical squamous cell carcinoma (CSCC); however, the dynamic role of the stromal and immune cells is still unclear in TME. We downloaded data from The Cancer Genome Atlas (TCGA) database and applied ESTIMATE and CIBERSORT algorithms to measure the quantity of stromal and immune cells and the composition of tumor-infiltrating immune cell (TIC) in 253 CSCC cases. The protein-protein interaction (PPI) network and Cox regression analysis presented the differentially expressed genes (DEGs). Then, C-C chemokine receptor type 7 (CCR7) was screened out as a prognostic marker by the univariate Cox and intersection analysis of PPI. Further analysis showed a positive correlation between the expression of CCR7 and the survival of CSCC patients. The result of the Gene Set Enrichment Analysis (GSEA) of genes in the high CCR7 expression group displayed a predominant enrichment in immune-related pathways. An enrichment in metabolic activities was observed in the low CCR7 expression group. CIBERSORT analysis showed a positive correlation between Plasma cells, CD8+ T cells, and regulatory T cells and the CCR7 expression, suggesting that CCR7 might play a crucial role in maintaining the immunological dominance status for TME. Therefore, the expression level of CCR7 might help predict the survival of CSCC cases and be an index that the status of TME transitioned from immunological dominance to metabolic activation, which presented a new insight into the treatment of CSCC.

The Role of Chemokines in Cervical Cancers

“…These changes were found for many cancers. Tian et al showed that CCR7 has the potential to be a prognosis marker for squamous cell cervical carcinoma cells and an index for tumor microenvironment change [85]. The CIBERSORT analysis showed a positive correlation between plasma cells, CD8 + T cells, and regulatory T cells and CCR7 expression within this study, suggesting that CCR7 could play a crucial role in maintaining the immunological dominance status for the tumor microenvironment [85].…”

Comprehensive analysis of lncRNA-mRNAs co-expression network identifies potential lncRNA biomarkers in cutaneous squamous cell carcinoma

“…UV irradiation, particularly UVB, is one of the classical cellular stressors causing DNA damage in skins, which receives chronic sun exposure, and ultimately leading to skin development of cSCC [ 16 ]. Therefore, many present studies investigated the potential oncogenic role of molecules and pathways in cSCC and tried to evaluate the promising diagnostic biomarkers value for cSCC [ 17 – 20 ]. It is currently aimed to elucidate DNA binding/differentiation 4 (ID4) function in cSCC development [ 21 ].…”

C-C Chemokine Receptor 7 in Cancer

“…High expression of these four genes—CCR7, programmed cell death-1 (PD-1), ZAP70 and CD28—was linked to a better 5 year overall survival [ 97 ]. Further analysis of TCGA and protein–protein interactions supported a positive correlation between CCR7 expression in cervical squamous carcinoma cells and patient survival, which was linked to a predominant augmentation of immune-related pathways, as opposed to a more metabolic pathway described for the low CCR7 expression group [ 98 ]. Another recent analysis of TCGA database suggested an immune gene-related prognostic model for cervical cancer that includes CCR7, along with CD3d, CD3e, β2 integrin, family with sequence similarity 133 member A and p53 for forecasting survival and immune responses for cervical cancer patients [ 99 ].…”