Co-expression network analysis identified atypical chemokine receptor 1 (ACKR1) association with lymph node metastasis and prognosis in cervical cancer
Affiliations: [a] Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China | [b] Department of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China
Correspondence:
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Corresponding author: Wenjun Cheng, Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210029, China. Tel.: +86 25 86862863; Fax: +86 25 86662863; E-mail: wenjunchengdoc@163.com.
Note: [1] These authors contributed equally to this work.
Abstract: Cervical cancer (CC) is one kind of female cancer. With the development of bioinformatics, targeted specific biomarkers therapy has become much more valuable. GSE26511 was obtained from gene expression omnibus (GEO). We utilized a package called “WGCNA” to build co-expression network and choose the hub module. Search Tool for the Retrieval of Interacting Genes Database (STRING) was used to analyze protein-protein interaction (PPI) information of those genes in the hub module. A Plug-in called MCODE was utilized to choose hub clusters of PPI network, which was visualized in Cytoscape. Clusterprofiler was used to do functional analysis. Univariate and multivariate cox proportional hazards regression analysis were both conducted to predict the risk score of CC patients. Kaplan-Meier curve analysis was done to show the overall survival. Receiver operating characteristic (ROC) curve analysis was utilized to evaluate the predictive value of the patient outcome. Validation of the hub gene in databases, Gene set enrichment analysis (GSEA) and GEPIA were completed. We built co-expression network based on GSE26511 and one CC-related module was identified. Functional analysis of this module showed that extracellular space and Signaling pathways regulating pluripotency of stem cells were most related pathways. PPI network screened GNG11 as the most valuable protein. Cox analysis showed that ACKR1 was negatively correlated with CC progression, which was validated in Gene Expression Profiling Interactive Analysis (GEPIA) and datasets. Survival analysis was performed and showed the consistent result. GSEA set enrichment analysis was also completed. This study showed hub functional terms and gene participated in CC and then speculated that ACKR1 might be tumor suppressor for CC.
