Qiu Xiao, Cheng Shen-Hong, Xu Fei, Yin Jin-Wen, Wang Li-Yang, Zhang Xin-You
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.
College of Basic Medicine, Army Military Medical University, Chongqing, China.
J Cancer. 2020 Feb 10;11(8):2348-2359. doi: 10.7150/jca.39723. eCollection 2020.
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.
结直肠癌(CRC)是最常见的癌症之一,也是全球癌症相关死亡的第四大主要原因。CRC成功治疗的障碍之一是高复发率。我们旨在构建加权基因共表达网络分析(WGCNA)以识别与CRC患者复发相关的关键模块和枢纽基因。我们首先使用微阵列数据GSE41258构建共表达网络并识别基因模块。此外,还进行了蛋白质与蛋白质相互作用(PPI)网络以筛选枢纽基因。为了验证枢纽基因,使用独立数据集GSE17536进行生存分析。此外,还使用另外两个数据库来研究枢纽基因的生存率和表达水平。进行基因集富集分析(GSEA)并结合基因本体论(GO)以进一步探索功能和机制。在我们的研究中,午夜蓝模块被确定为显著模块,筛选出15个枢纽基因,其中4个在PPI网络中被确定为枢纽节点。在测试数据集中,我们发现MYL9和CNN1的高表达与CRC患者较短的生存时间显著相关。GO分析表明,MYL9和CNN1富集于“肌肉系统过程”和“细胞骨架蛋白结合”。GSEA发现这两个枢纽基因富集于“癌症通路”和“钙信号通路”。总之,我们的研究表明,MYL9和CNN1是与CRC复发相关的枢纽基因,这可能有助于提高CRC患者的无复发生存时间。