GC, also known as stomach cancer, seriously affects public health and life safety because most of patients admitted to the hospitals are advanced GC [1]. At present, the common treatment for GC includes surgery, chemotherapy, radiotherapy, targeted and immunotherapy, among which surgery is the most effective way to treat GC, but the recurrence rate is high [7]. Although cancer mortality has slowly decreased since 1991, it remains a challenge to explore potential therapeutic targets of GC due to increased drug resistance and heavy economic burden [8]. Therefore, we integrated four sets of microarray datasets from GEO databases and identified a total of 128 DEGs by means of two bioinformatics analysis methods, which mainly involved in ECM process and metabolism by cytochrome P450.
ECM is composed of different macromolecular substances secreted by cells into extracellular matrix, including collagen, proteoglycans/glycosaminoglycans and fibronectins, which forms a three-dimensional network around the cell [9, 10]. ECM also undertakes a variety of biological functions, such as cellular differentiation, cell growth, cell survival, cell migration, homeostasis and morphogenesis [10]. Tumor-related microenvironment is mainly composed of ECM, while the imbalance of ECM can lead to the development of tumor cells [11]. For example, the imbalance of ECM can prevent the behavior regulation of stromal cells, and promote tumor-related angiogenesis and inflammatory reaction, allowing a favorable microenvironment for tumor growth [11]. Therefore, the abnormal ECM dynamics is one of the common clinical causes of cancer [12].
Moreover, cytochrome P450s (P450s) consists of various hemoproteins and belongs to the largest and most functionally versatile superfamily. The functional range of P450 activity is of great significance in both microorganisms and humans[13]. Many studies have found that different members of the P450s family play important roles in activating different carcinogenic compounds [14–16]. P450s can not only promote the metabolism of carcinogens by regulating polycyclic aromatic hydrocarbon metabolism [17–20], but also affect the tumor metastasis and growth-related inflammatory process [21]. Hence, P450s plays an essential role in tumorigenisis, cancermetastasis, chemoprevention and chemotherapy [16]. Most pre-existing GC prognostic models have limitations since there is only one gene or mRNA invovled in the model [22]. The clinical outcome of GC is found to be associated with multiple genes. In the current study, overlapped DEGs including ASPM, COL11A1 and CDC20 genes were noticed by using WGCNA and co-expression analysis. These DEGs not only controled the number of genes in the prognosis model, but also improved the specificity and accuracy of the model. To further explore the relationship of ASPM, COL11A1 and CDC20 with GC, data from TCGA database was used to draw the heatmap of their expression in tumor tissues and normal tissues. The results showed a significant high expression of ASPM, COL11A1 and CDC20 in tumor tissues. After that, LASSO Cox regression analysis was used to screen COL11A1 and CDC20 genes,and constructed a prognostic risk model. According to RS, cancer patients were divided into high-risk group and low-risk group. The results of survival curve demonstrated that the prognosis of these two groups was remarkably different. The results of ROC curve showed that the RS predicted the 5-year survival rate of GC patients, while the multivariate Cox regression analysis reflected that RS could be used as an independent prognostic indicator. Several studies have shown that COL11A1 gene can promote the cell proliferation, migration and invasion of GC cells [23]. Researchers from a previous study have also found an overexpressed COL11A1 gene in a study of recurrent non-small cell lung cancer, which can promote cell proliferation, migration, invasion and drug resistance [24]. Additionally, COL11A1 gene may also contribute greatly to the occurrence and development of ovarian cancer, breast cancer, pancreatic cancer and esophageal squamous cell carcinoma [25–28]. Moreover, the carcinogenic effect of CDC20 gene can cause ubiquitination and degradation of securin, leading to chromosome segregation and blockage of cell cycle, which means CDC20 may be a promising target for anti-tumor therapy of GC [29, 30]. Another study has reported that the phosphorylation of Mcl-1 can induce CDC20 gene to initiate cell apoptosis [31]. In addition, 2 core genes (COL11A1 and CDC20) were found to be significantly differentially expressed between gastric cancer tissue and normal gastric tissue using qRT-PCR. Therefore, from the clinical and bioinformatics point of view, COL11A1 and CDC20 genes can be used as prognostic risk markers of GC.