High expression of centromere protein N as

novel biomarkers for gastric adenocarcinoma

Xiaojie Wang^1,2, Keyuan Zhang^1,2, Cun Fu ^1,2, Fei Wu¹, Junjie Zhang¹, Bin Han³, Hai Pan⁴, Lan Luan^1*

¹ Department of Pathology, Central Hospital Affiliated to Shenyang Medical College, Shenyang, China.

² Basic Medical School, Shenyang Medical College, Shenyang, China.

³ Department of Urology, Shengjing Hospital of China Medical University, Shenyang, China.

⁴ Central Laboratory, Central Hospital Affiliated to Shenyang Medical College, Shenyang, China.

* Correspondence: Lan Luan luanlan33@symc.edu.cn

Keywords: CENPN; gastric adenocarcinoma; proliferation; cycle; apoptosis.

Abstract

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

Methods: Data from The Cancer Genome Atlas and Genotype Tissue Expression were used to examine the expression of CENPN in STAD and neighboring tissues. Xiantao Academic was used to perform Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis on CENPN. By reviewing TCGA database, the relationship between CENPN expression and immune cell infiltration was assessed. The expression of CENPN in STAD and surrounding tissues was confirmed by immunohistochemical staining, and the correlation between CENPN expression and clinicopathological characteristics was examined. CENPN was depleted in AGS cells with siRNAs, and its impact on proliferation was measured by CCK-8 and EdU assays. Following siRNA transfection, flow cytometry was performed to identify cell cycle and apoptotic alterations in AGS cells.

Results: CENPN was highly expressed in STAD tissues. The degree of invasion, TNM stage, and lymph node metastases were all substantially linked with CENPN expression. GO|KEGG Enrichment analysis revealed that CENPN was essential for the cell cycle, DNA replication, chromosomal segregation, and nuclear division, among other important signaling pathways. Further investigation revealed a positive correlation between CENPN expression and Th2 cells and NK CD56dim cells and a negative correlation between CENPN expression and mast cells , pDC cells,NK cells and B cells. When CENPN expression in AGS cells was knocked down, cell proliferation dramatically reduced, and the percentage of cells in the S and G2-M phases decreased significantly. In addition, compared to the control group, the proportion of apoptotic AGS cells significantly increased after downregulating the expression level of CENPN.

Conclusion: According to our data, CENPN acts as an oncogene in STAD and may be a viable therapeutic target.