GC is still a disease with a high prevalence and mortality rate. Its treatment is mostly based on surgery, supplemented by radiotherapy, chemotherapy, targeted therapy, and gene therapy. However, its survival rate is still very low, with a 5-year survival rate still below 30% [12]. In this regard, it is important to study GC progression as well as pathogenesis in order to guide drug interventions, suggest prognosis or improve survival. The rapid development of platforms focusing on high-throughput detection of gene expression in disease progression has provided new research directions and new preventions for cancer diagnosis, treatment and prognosis. In this study, a total of 90 DEGs were screened, including 33 up-regulated genes and 57 down-regulated genes. These up-regulated genes are mainly involved in ion transport in biological processes and response to viruses, while the down-regulated genes are mainly involved in cell proliferation and division. Among these genes, seven genes were highly expressed in tumor tissues and significantly associated with poor overall survival in GC patients, including CEACAM7, THBS2, TREM2, MFAP2, BGN, MMP1 and NUSAP1. The pathogenesis of cancer is multifactorial and is associated with the interaction of genetic, environmental and lifestyle factors. Among them CEACAM7 gene it is a member of a specific CEA gene family of carcinoembryonic antigen (CEA) family genes, CEA cell adhesion molecule-7 (CEACAM-7), which is regulating normal cell differentiation [13].Abnormalities in CEACAM-7 expression have been shown to occur early in colorectal tumorigenesis; changes in the expression of adenomas, proliferative polyps [13, 14] .
So far, there is little information on the expression of CEACAM7 in gastric non-neoplastic and neoplastic lesions. Meanwhile, related studies have shown that the expression of CEACAM7 is closely related to the differentiation of gastric cancer. the expression of CEACAM7 gradually increases during the development of gastric cancer and can be used as a prognostic predictor for gastric cancer patients after surgery [15, 21]. THBS2 is platelet-responsive protein 2, a protein that may regulate the cell surface properties of mesenchymal cells and is involved in cell adhesion and migration, and some studies have shown that that patients with low THBS2 expression have a better prognosis and may be studied as a signature protein for gastric cancer prognosis [15]. Trigger receptor expressed on myeloid cells 2 (TREM2) is a member of the immunoglobulin superfamily, which can form a complex of signaling pathways with TYRO protein tyrosine kinase binding proteins on the cell membrane, and one study found significant differences in the expression of TREM2 in gastric cancer and paraneoplastic tissues, and TREM2 in prognostic role in GC found that TREM2 inhibits T cell proliferation and is a negative regulator of tumor immunity,It was also found that TREM2 expression was higher in lung cancer patients than in healthy individuals, and TREM2 expression may be a potent prognostic biomarker for GC [16].
Recently, MFAP2 has been found to regulate the deposition of pro-elastin into microfibrils and participate in the formation of elastic fibers. It is thought to be a co-expressed gene of the NF-kB/Snail/YY1/RKIP circuit, with upregulated expression in tumor tissues; the extent of this upregulation is specific evidence of lymph node metastasis, and MFAP2 expression is significantly elevated in gastric tumor tissues compared to adjacent normal tissues, correlating with poor prognosis in GC patients [17].In a study by Chen et al. BGN overexpression was found to be associated with GC poor prognosis and resulted in elevated levels of immune infiltration of cytotoxic cells, DCs, macrophages, neutrophils, Th17 cells, and Th2 cells [18], revealing that BGN may be a potential GC biomarker. Metallo-matrix proteinase 1 (MMP1),a member of the zinc-dependent endopeptidase family, has been shown to be closely associated with the migration and invasion of many cancers [19]. Recent studies have found that MMP1 can also promote the proliferation of cancer cells, and in a study by Liu et al. it was demonstrated that MMP1 can promote the proliferation and metastasis of hepatocellular carcinoma cells [20], while the poor prognostic outcome of high MMP1 expression in gastric cancer tissues in the present study suggests that MMP1 may become a signature gene for GC prognosis. NUSAP1 is a binding protein of Yes-associated protein1 (YAP1), which is a major player in the Hippo pathway and has an important role in tumor initiation, progression and metastasis in many cancers, including GC. The pro-oncogenic effect of NUSAP1 on tumor cell growth, migration and invasion was found to be mainly regulated by YAP1. Meanwhile, the aberrant expression of NUSAP1 and YAP1 was highly correlated in tumor cell lines and tissues. Therefore the role of NUSAP1 in the development of gastric carcinogenesis is significant, and thus a new target for GC therapy [20].