Integrating WGCNA and SVM-RFE identifies hub molecular biomarkers driving ischemic stroke progression

Stroke is the second most common cause of death worldwide and the leading cause of long-term severe disability with neurological impairment worsening within hours after stroke onset and being especially involved with motor function. So far, there are no established and reliable biomarkers to prognose stroke. Early detection of biomarkers that can prognose stroke is of great importance for clinical intervention and prevention of clinical deterioration of stroke.

TGSE119121 dataset was retrieved from the Gene Expression Integrated Database (Gene Expression Omnibus, GEO) and weighted gene co-expression network analysis (WGCNA) was conducted to identify the key modules that could regulate disease progression. Moreover, functional enrichment analysis was conducted to study the biological functions of the key module genes. The GSE16561 dataset was further analyzed by the Support Vector Machines coupled with Recursive Feature Elimination (SVM-RFE)algorithm to identify the top genes regulating disease progression. The hub genes revealed by WGCNA were associated with disease progression using the receiver operating characteristic curve (ROC) analysis. Subsequently, functional enrichment of the hub genes was performed by deploying gene set variation analysis (GSVA). The changes at gene level were transformed into the changes at pathway level to identify the biological function of each sample. Finally, the expression level of the hub gene in the rat infarction model of MCAO was measured using RT-qPCR for validation.

WGCNA analysis revealed four hub genes: DEGS1, HSDL2, ST8SIA4 and STK3. The result of GSVA showed that the hub genes were involved in stroke progression by regulating the p53 signal pathway, the PI3K signal pathway, and the inflammatory response pathway. The results of RT-qPCR indicated that the expression of the four HUB genes was increased significantly in the rat model of MCAO.

Several genes, such as DEGS, HSDL2, ST8SIA4 and STK3, were identified and associated with the progression of the disease. Moreover, it was hypothesized that these genes may be involved in the progression stroke by regulating the P53 signal, the PI3K signal, and the inflammatory response pathway, respectively. These genes have potential prognostic value and may serve as biomarkers for predicting stroke progression.