Overexpression of APOA2 is Associated with Progression and Poor Prognosis in Gastric Cancer
Authors: Bao Machicheng , Xu Jing , Liu Jia 
Published: February 2022

Abstract
Background: Gastric cancer is a malignant tumor originating from gastric mucosal epithelium, and more than 90% of them are gastric adenomas. At present, surgical treatment is the main method to cure gastric cancer. We were able to find through bioinformatics that many genes are aberrantly expressed in gastric cancer. APOA2, a gene in the apolipoprotein A family, is the major apolipoprotein of high-density lipoprotein (HDL). APOA2 is composed of 77 amino acid residues of two polypeptide chains and exists in the plasma dimer form. APAO2 is closely related to obesity, atherosclerosis, diabetes, and hyperlipidemia, and can also be used as a diagnostic marker for diseases such as pancreatic cancer and liver cancer. Objective: To investigate the expression and mechanism of APOA2 in gastric cancer cells, and to find out miRNAs that target and regulate APOA2. Methods: The clinical data of gastric cancer were downloaded using GCTA database, the relationship between APOA2 and the occurrence and development of gastric cancer was analyzed using bioinformatics, and the clinical samples were verified. Its potential miRNA regulatory mechanism was also sought. The correlation between APOA2 expression and clinicopathological parameters in clinical cases with different stage grades was statistically analyzed with t-test and chi-square test. The log-rank test was used to predict and find the relationship between APOA2 expression and overall survival (OS) and relapse-free survival (RFS). Gene set enrichment analysis (GSEA) was performed to screen KEGG pathways associated with APOA2 expression during gastric carcinogenesis. MiRNA expression data of gastric cancer were downloaded from the TCGA database, their differential expression was analyzed, and miRNAs targeting APOA2 expression were screened, along with their relationship with gastric cancer progression and prognosis. Paraffin sections of gastric cancer tissues and normal gastric tissues were collected in 5 cases each, and the expression of APOA2 in these samples was verified by PCR.Results: APOA2 expression was significantly different between gastric cancer tumor samples and normal tissue samples by analysis of TCGA database samples (p < 0.001). Cox regression analysis showed that upregulation of APOA2 expression was associated with overall survival (OS) and recurrence-free survival (RFS) in gastric cancer. In addition, miR-27b-3p targeted up-regulation of APOA2 and resulted in decreased OS and RFS. APOA2 was found to be significantly enriched in the "DNA replication", "cell cycle" pathways by GSEA analysis. Conclusion: APOA2 is involved in the whole process of gastric cancer development and is regulated by miR-27b-3p, and affects the overall survival and recurrence-free survival of patients, which mainly promotes the progression of gastric cancer by affecting the "DNA replication" and "cell cycle" of cancer cells. APOA2 is expected to be a promising prognostic biomarker and candidate therapeutic target for gastric cancer. Keywords: APOA2, gastric cancer, miR-27b-3p