High expression of centromere protein N as novel biomarkers for gastric adenocarcinoma

The role and mechanism of centromeric protein N (CENP-N), which has been associated with the development of various cancer types, are yet unclear in stomach adenocarcinoma (STAD).

According to our data, CENP-N acts as an oncogene in STAD and may be a viable therapeutic target.

Data from the Cancer Genome Atlas and Genotype-Tissue Expression were used to determine whether CENP-N expression was altered in STAD tumors compared to normal tissues. Xiantao was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis on CENP-N. The relationship between CENP-N expression and immune cell infiltration was assessed using TCGA database. The expression of CENP-N in STAD and surrounding tissues was confirmed using immunohistochemical staining and the correlation between CENP-N expression and clinicopathological characteristics was examined. The effects of CENP-N knockdown by siRNA on proliferation were measured by CCK-8 and EdU assays in AGS cells. Following siRNA transfection, flow cytometry was performed to evaluate cell cycle and apoptotic alterations in AGS cells. The effect of CENP-N knockdown on the expression level of related proteins was detected by Westren blot.

CENP-N was highly expressed in STAD tissues, which was confirmed by our immunohistochemistry results. The degree of invasion, TNM stage, and lymph node metastases were all strongly associated with CENP-N expression. CENP-N was essential for the cell cycle, DNA replication, chromosomal segregation, and nuclear division; there was a positive correlation between CENP-N expression and infiltrating Th2 and NK CD56dim cells and a negative correlation between CENP-N expression and mast, pDC, NK, and B cell infiltration. When CENP-N expression in AGS cells was knocked down, cell proliferation dramatically reduced (p < .05) and the percentage of cells in the S and G2-M phases decreased significantly (p < .05). Silencing CENP-N significantly promoted the apoptosis of AGS cells (p < .05). Mechanistic investigations showed that silencing CENP-N expression may inhibit STAD proliferation through the Cyclin E1 and promote STAD apoptosis through the Bcl-2/Bax.