Abstract:Weighted gene co-expression network analysis was used to identify the hub genes related to the occurrence and development of esophageal cancer for exploring the potential targets of anti-esophageal cancer effects of Poria cocos, and open up new avenues for the clinical diagnosis and treatment of esophageal cancer. Firstly, the effective active components of Poria cocos and their corresponding targets were screened out from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The protein interaction network map of the targets was constructed with the STING tool, and the first 6 candidate drug action targets were identified by Cytoscape. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were used to explore the differentially expressed genes between normal tissues and esophageal cancer tissues. Genes related to esophageal cancer were obtained by WGCNA. The potential targets of anti-esophageal cancer effects were preliminarily determined by comparing the esophageal cancer-related genes with the first six drug targets of Poria cocos. The RT-PCR method was used to detect the expression of the selected hub genes in mouse model cancer cells. A total of 34 kinds of effective active components of Poria cocos as well as 17 corresponding targets were generated, among which the main candidate drug targets were CHRM1, NCOA2, PGR, ADRA1B, ADH1B, and PTGS2. ADH1B is demonstrated to be a potential therapeutic target for anti-esophageal cancer of Poria cocos. A total of 2,394 differentially expressed genes were screened out in the TCGA-ESCA data set, and 1,504 differentially expressed genes were screened out in the GSE22954 dataset. Hub genes DLGAP5, MCM2, CCNA2, CDK1, TPX2, TRIP13, KIF23, KIF2C, CENPF, and CHAF1A were screened out. The expression level of CHAF1A and MCM2 influences the prognosis of patients with esophageal cancer. RT-PCR results showed that the expression of CDK1, CHAF1A, TPIP13, and MCM2 genes under treatment with different concentrations of Poria cocos extracts was significantly different from the control, indicating that CDK1, CHAF1ATPIP13, and MCM2 are the main target during Poria cocos in the treatment of esophageal cancer.