Genome-Scale Analysis Identified NID2, SPARC, and MFAP2 as Prognosis Markers of Overall Survival in Gastric Cancer

Abstract

BACKGROUND Gastric cancer is the most common gastrointestinal tumor, and the rates of recurrence and metastasis are high. Research results on molecular biomarkers used for prognosis of gastric cancer remain inconclusive. This study aimed to explore the gene expression module of gastric cancer and to determine potential prognostic biomarkers. MATERIAL AND METHODS Three microarray datasets (GSE13911, GSE79973, and GSE29272) from Gene Expression Omnibus (GEO), including 206 pairs of gastric tumors and adjacent normal samples, were used for analysis of differentially expressed genes (DEGs). The 3 microarray datasets yielded 144 genes associated with the progression and prognosis of gastric cancer. After this, a risk score model was developed for result validation using an independent dataset from The Cancer Genome Atlas. RESULTS The validation of the independent dataset showed significantly increased NID2, SPARC, and MFAP2 expression in gastric tumor tissues, which were associated with poor outcomes in gastric cancer patients. Moreover, the high risk score obtained was associated with poor overall survival (HR: 1.787; 1.069-2.986; P=0.027). Subgroup analyses revealed that these significant prognostic values were detected in patients aged <65.0 years, tumors in the antrum/distal colon, grade 3 tumors, or TNM-M0 stages of cancer. CONCLUSIONS The findings of this study show that NID2, SPARC, and MFAP2 are upregulated in gastric tumor tissues and are significantly associated with poor overall survival. Therefore, the predictive values of the risk score model employed for the prognosis of gastric cancer could be improved by using these 3 upregulated DEGs.

Figure 1

The details regarding the expression data from primary gastric tumors and adjacent normal samples in 4 subsets of 3 datasets.

Figure 2

Identification of differentially expressed genes. Visualization of the identified differentially expressed genes was performed by volcano plots. Dots represent genes with color coding: red indicates upregulated, blue indicates downregulated, and black indicates genes that are not differentially expressed.

Figure 3

Venn diagram of the overlapping parts of the 4 subsets of 3 datasets of differentially expressed genes. Sixty-one genes were upregulated and 83 were downregulated.

Figure 4

Overall survival according to the expression of NID2, SPARC, and MFAP2. Red line indicates high expression and blue line indicates low expression.

Figure 5

Overall survival according to the risk scores after propensity score analysis. Red line indicates high risk score and blue line indicates low risk score.