Prognostic marker identification based on weighted gene co-expression network analysis and associated in vitro confirmation in gastric cancer

Abstract

The aim of this study was to explore the potential molecular mechanisms of Gastric cancer (GC) and identify new prognostic markers for GC. RNA sequencing data were downloaded from the Gene Expression Omnibus database, and 418 differentially expressed genes (DEGs) were screened. Weighted correlation network analysis (WGCNA) was performed to identify six hub modules related to the clinical features of GC. Cytoscape software was used to identify five hub genes in the coexpression network, including CST1, CEMIP, COL8A1, PMEPA1, and MSLN. The TCGA database was used to verify hub gene expression in GC. The overall survival in the high CEMIP expression group was significantly lower than that of patients in the low CEMIP expression group. CEMIP expression was also found to be negatively correlated with B cell and CD4 + T cell infiltration. Further, associated in vitro experiments confirmed that CEMIP downregulation suppressed the proliferation and migration of GC cells and impaired the chemoresistance of GC cells to 5-fluorouracil.Our study effectively identified and validated prognostic biomarkers for GC, laying a new foundation for the therapeutic target, occurrence, and development of gastric cancer.

ANLN, COL8A1, MMP3, MMP14 and WNT5A, as potential diagnostic and therapeutic targets for early-stage colorectal cancer: evidence from integrated bioinformatics analysis

“…COL8A1 overexpression is related to the occurrence of CRC 40 , gastric cancer 41 , hepatocellular carcinoma 42 and breast cancer 43 . ANLN, COL8A1, MMP3, MMP14 and WNT5A are not only closely related to the occurrence and progress of CRC, but also play an important role in other neoplastic diseases.…”

Integrative analysis identifies key genes related to metastasis and a robust gene-based prognostic signature in uveal melanoma

“…After that, we could input the file of the network obtained from the String database into the Cytoscape software [ 20 ], which is widely used for the investigation of genes and gene–gene interactions in cancer research. Moreover, there is a useful and widely used tool (cytohubba) inside the Cytoscape software for identifying the key nodes (genes) in a gene interaction network [ 21 , 22 ] and we applied this tool to identify the top 50 hub genes in the two modules of interest. There are several methods inside the cytohubba tool and we chose the MCC method to identify hub genes, which could be achieved by simple selection on the page of the Cytoscape software.…”

CEMIP, a Promising Biomarker That Promotes the Progression and Metastasis of Colorectal and Other Types of Cancer

“…In non-small lung cancer cells, CEMIP-induced EMT has been found to be mediated via PI3K/Akt signaling [ 19 ], a downstream effector of EGFR signaling. Consistent with an EMT-inducing role, the knockdown of CEMIP in a number of settings has been reported to increase the epithelial characteristics of cells and decrease their mesenchymal properties, as evidenced by the increased expression of E-Cadherin, ZO-1, and occludin and by a decrease in vimentin, N-cadherin, and snail expression [ 8 , 25 , 29 , 41 , 73 ].…”

“…Accordingly, a number of observations suggest that targeting CEMIP expression and activity can re-sensitize tumors to therapeutic intervention. In the context of chemotherapy, the downregulation of CEMIP increases the sensitivity of resistant gastric cancer cells to the chemotherapeutic agent 5-fluorouracil (5-FU), indicating the potential utility of using CEMIP inhibitors in combination with chemotherapy [ 25 , 72 ]. Resistance to tyrosine kinase inhibitors that target the MET oncogene ensues when neuropilin-2 is downregulated.…”

“…Some studies have indicated that CEMIP expression is further increased in metastatic lesions of CRC compared with the primary tumor [ 8 , 17 , 18 ]. A broad body of evidence also documents the association between CEMIP expression, and poor prognosis and metastasis in other types of human cancer, including lung [ 19 , 20 , 21 ], gastric [ 22 , 23 , 24 , 25 ], pancreatic [ 26 ], brain [ 27 , 28 ], breast [ 5 , 10 , 29 , 30 ], and papillary thyroid [ 31 ] cancers, as well as in cholangiocarcinoma [ 14 ], hepatocellular carcinoma (HCC) [ 32 , 33 ], laryngeal [ 34 ], and oral squamous cell carcinoma [ 35 ]. Again, CEMIP has also been shown to be an independent prognostic factor in NSCLC [ 19 , 21 ], gastric cancer [ 24 , 25 ], pancreatic ductal adenocarcinoma [ 26 ], laryngeal squamous cell carcinoma [ 34 ], osteosarcoma [ 36 ], and HCC [ 33 ].…”