CEP55 as a prognostic indicator and a predictive marker in oral squamous cell carcinoma

Abstract

Objective: To investigate the role of CEP55 in the occurrence and development of oral squamous cell carcinoma (OSCC). Materials and Methods: Through the utilization of the online OSCC database and bioinformatic analysis, we examine CEP55 expression and its correlation with prognosis, pathways, and immune infiltration. CEP55 and other biomarkers were stained using immunohistochemical methods in 57 cases of OSCC and 44 cases of adjacent paired tissues, demonstrating the clear involvement of CEP55. Results: The expression levels of CEP55 were significantly higher in OSCC tissues compared to normal tissues. Additionally, higher levels of CEP55 were associated with a worse prognosis. CEP55 expression levels were significantly higher in OSCC tissues compared to normal tissues. Additionally, higher levels of CEP55 were associated with a worse prognosis. GSEA results indicated a correlation between CEP55 and the cell cycle. Immunohistochemical staining revealed a significant positive correlation between CEP55 and cell cycle-related protein markers (PCNA, P16, P21, and P53). Furthermore, CEP55 was found to significantly inhibit tumor immune infiltration. As a result, CEP55 expression decreased infiltration of 9 types of immune cells (iDC, mast cells, pDC, DC, Th17 cells, TFH, Treg, T cells, and neutrophils), while increasing infiltration of only 3 types of immune cells (Tcm, T Helper cells, and Th2 cells). Conclusion: The results suggest that CEP55 plays a crucial role in the progression of OSCC promoting cell cycle progression and suppressing immune infiltration.

Keywords: CEP55; OSCC; cell cycle; immune infiltration; prognosis.

Figure 1

Comparison of CEP55 between OSCC and normal samples. (A-B) Comparison of CEP55 mRNA levels between normal and OSCC tissue samples as a whole (A) and after sample pairing (B) in TCGA database, unpaired t-test vs. paired t-test, respectively. (C-D) Comparison of CEP55 mRNA levels between normal and OSCC tissue samples as a whole in the GEO and TCGA databases (C. GSE30748; D. GSE37991), unpaired t-test. (E) Paired IHC images of CEP55 in OSCC and paracancerous tissues. (F-G) Unpaired t-test versus paired t-test of CEP55 protein levels between OSCC and paracancerous tissues.

Figure 2

Survival analysis based on CEP55 mRNA levels. (A-C) Overall survival (A), disease-specific survival (B), and progression-free interval survival (C) in the CEP55 high-expression group versus the low-expression group, Log-rank test. (D) ROC curves for the variability of the degree of CEP55 elevation in OSCC.

Figure 3

Screening and enrichment analysis of differentially expressed genes (DEGs) between high and low expression groups divided by CEP55 mRNA levels. (A-B) Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Analyses of Differentially Expressed Genes in OSCC CEP55 High and Low Expression Groups. (C-D) Gene Set Enrichment Analysis (GSEA) Showing Activation and Inhibition Pathways of CEP55 High Expression in OSCC. (E) Heatmap of CEP55 Up-regulated Differentially Expressed Genes (DEGs) and Down-regulated Differentially Expressed Genes in OSCC, *** p < 0.001.

Figure 4

CEP55 expression and tumor immune infiltration. To this end, we have analyzed the stromalScore, immuneScore, and ESTIMATEScore of CEP55 expression in high and low expression groups. Furthermore, we have investigated the relationship between CEP55 and the infiltration level of various immune cells. (A) StromalScore, ImmuneScore, and ESTIMATEScore of the high and low expression groups of CEP55, * p < 0.05, ** p < 0.01, ns= no significance. (B-C) Correlation between CEP55 expression and the infiltration level of various immune cells, * p < 0.05, *** p < 0.001, ns= no significance.

Figure 5

CEP55 and OSCC Cell Proliferation Markers P16, P21, P53, and PCNA. (A) IHC images of OSCC tissues in the high and low CEP55 expression groups. The IHC staining markers include CEP55 and proliferation markers P16, P21, P53, and PCNA. (B) Unpaired T-test of the protein levels of proliferation markers in OSCC tissues between the high and low CEP55 expression groups.

Figure 6

CEP55 and OSCC Cell Proliferation Markers TGFB1, MAPK, p-AKT, and β-catenin. (A) IHC images of OSCC tissues in the high and low CEP55 expression groups. The IHC staining markers include CEP55 and TGFB1, MAPK, p-AKT, and β-catenin. (B) Unpaired T-test of the protein levels of TGFB1, MAPK, p-AKT, and β-catenin in OSCC tissues between the high and low CEP55 expression groups.

Figure 7

IP images of OSCC tissues in the high and low CEP55 expression groups. The IP staining markers include immune phenotype markers CD3 (green), CD4 (red), CD8 (pink), and DAPI (blue). The scale bar is indicated in the figure.