Systematic Analysis of Chemokines Reveals CCL18 is a Prognostic Biomarker in Glioblastoma

Wenqing Gao,1,* Yuanyuan Li,1,* Teng Zhang,1 Jianglong Lu,2 Jiasong Pan,1 Qi Qi,1 Siqi Dong,3 Xiangjun Chen,3,4 Zhipeng Su,2 Jixi Li1,4 1State Key Laboratory of Genetic Engineering, Department of Neurology, Huashan Hospital and Institute of Neurology, School of Life Sciences, Shanghai Engineering Research Center of Industrial Microorganisms, Fudan University, Shanghai, 200438, People’s Republic of China; 2Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China; 3Department of Neurology, Huashan Hospital and Institute of Neurology, Fudan University, Shanghai, 200040, People’s Republic of China; 4National Center for Neurological Disorders, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhipeng Su; Jixi Li, Email drsuzhipeng@wmu.edu.cn; lijixi@fudan.edu.cnBackground: Glioblastoma (GBM) is the most common and aggressive brain tumor in adults, in which chemokines are often upregulated and may play pivotal roles in their development and progression. Chemokines are a large subfamily of cytokines with leukocyte chemotactic activities involved in various tumor progression. However, gene expression patterns of the chemokines on a global scale were not known in GBM.Methods: Differentially expressed chemokine genes in glioma and normal samples were screened by using The Cancer Genome Atlas (TCGA) database. Cox regression identified the prognosis-related genes in each glioma subtype. The protein expression levels of chemokines in 72 glioma tissues were detected by ELISA.Results: We found that the transcripts of seven chemokines, including CCL2, CCL8, CCL18, CCL28, CXCL1, CXCL5, and CXCL13, were highly expressed in GBM that evidenced by involving immune cell infiltration regulation and accompanied with worse outcomes of GBM patients. The prognostic nomogram construction demonstrated that CCL18 held the highest risk score in patients with GBM. Furthermore, experiments on 72 glioma tissue samples confirmed that CCL18 protein expression was positively associated with tumor grade and IDH1 status but inversely with glioma patients’ overall survival (OS).Conclusion: Our study reveals comprehensive and comparable roles of chemokine members in glioblastoma, and identified CCL18 as a critical driver of GBM malignant behaviors, therefore providing a potential target for developing prognosis and therapy in human glioblastoma.Keywords: chemokines, GBM, biomarker, overall survival, prognosis