1. Department of Hematology, Shenzhen People's Hospital, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, China
2. College of Basic Medicine, Army Military Medical University, Chongqing, China
3. Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China
4. Department of Gastroenterology, Shenzhen People's Hospital, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, China
Colorectal cancer (CRC) is one of the most common carcinomas and the fourth leading cause of cancer-related death worldwide. One of the obstacles in the successful treatment of CRC is a high rate of recurrence. We aimed to construct weighted gene co-expression network analysis (WGCNA) to identify key modules and hub genes in association with recurrence in CRC patients. We firstly used the microarray data, GSE41258, to construct a co-expression network and identify gene modules. Furthermore, protein and protein interaction (PPI) network was also performed to screen hub genes. To validate the hub genes, an independent dataset GSE17536 was used for survival analyses. Additionally, another two databases were also performed to investigate the survival rates and expression levels of hub genes. Gene set enrichment analyses (GSEA) combined with gene ontology (GO) were performed to further explore function and mechanisms. In our study, the midnightblue module was identified to be significant, 15 hub genes were screened, four of which were identified as hub nodes in the PPI network. In the test dataset, we found higher expression of MYL9 and CNN1 were significantly associated with shorter survival time of CRC patients. GO analyses showed that MYL9 and CNN1 were enriched in “muscle system process” and “cytoskeletal protein binding”. GSEA found the two hub genes were enriched in “pathways in cancer” and “calcium signaling pathway”. In conclusion, our study demonstrated that MYL9 and CNN1 were hub genes associated with the recurrence of CRC, which may contribute to the improvement of recurrence-free survival time of CRC patients.
Keywords: colorectal cancer (CRC), weighted gene co-expression network analysis (WGCNA), recurrence, hub gene