Demethylation and Overexpression of CSF2 are Involved in Immune Response, Chemotherapy Resistance, and Poor Prognosis in Colorectal Cancer

Zongbin Xu,1,* Yiyi Zhang,1,* Meifang Xu,2,* Xin Zheng,2 Mengxin Lin,3 Jie Pan,4 Chengwei Ye,1 Yu Deng,1 Caiyun Jiang,1 Yu Lin,1 Xingrong Lu,1 Pan Chi1 1Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China; 2Department of Pathology, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China; 3Department of Oncology, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China; 4Department of Emergency Surgery, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xingrong Lu; Pan ChiDepartment of Colorectal Surgery, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou City 350001, Fujian, People’s Republic of ChinaTel +86-591-83357896-8410Fax +86-591-87113828Email fjxhlxr@163.com; chipan363@163.comPurpose: This study aimed to evaluate the role of colony-stimulating factor 2 (CSF2) in chemotherapy resistance, prognosis, and immune response and to identify its possible mechanisms underlying drug resistance.Methods: Drug-resistant cell lines were obtained by successively increasing drug concentration. RNA-Seq was performed to screen hub genes. CSF2 expression was analyzed via immunohistochemistry. Moreover, The Cancer Genome Atlas (TCGA), Tumor Immune Estimation Resource (TIMER) dataset, and R2 platform were used to explore the correlations among CSF2 expression, prognosis, and immune response.Results: RNA-Seq indicated that microRNAs in cancer, P53 signaling pathway, and cell cycle were associated with FOLFOX chemotherapy resistance. Protein-protein interaction (PPI), molecular complex detection (MOCDE), and qRT-PCR analysis verified CSF2 as the hub gene in chemotherapy resistance. Moreover, CSF2 expression was lower in the normal tissue than in the cancerous tissue (P<0.05). Higher expression of CSF2 was associated with poor