Overexpression of COL3A1 confers a poor prognosis in human bladder cancer identified by co-expression analysis

// Lushun Yuan 1, * , Bo Shu 1, 2, * , Liang Chen 1 , Kaiyu Qian 1, 3 , Yongzhi Wang 1 , Guofeng Qian 4 , Yuan Zhu 5 , Xinyue Cao 6 , Conghua Xie 7 , Yu Xiao 1, 5, 6 and Xinghuan Wang 1 1 Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China 2 Department of Urology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China 3 Department of Urology, The Fifth Hospital of Wuhan, Wuhan, China 4 Department of Endocrinology, The First Affiliated Hospital of Zhejiang University, Hangzhou, China 5 Laboratory of Precision Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China 6 Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, China 7 Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China * These authors have contributed equally to this work Correspondence to: Yu Xiao, email: yu.xiao@whu.edu.cn Xinghuan Wang, email: wangxinghuan@whu.edu.cn Keywords: COL3A1, bladder cancer, co-expression analysis, MAPK, clinicopathology Received: May 17, 2017      Accepted: June 30, 2017      Published: July 28, 2017 ABSTRACT Human bladder cancer (BCa) is one of the worldwide cancers in men and women populations, with the etiology and mechanism unknown. In our study, we constructed a weighted gene co-expression network to identify gene modules associated with the progression of BCa (n = 93). In the significant module (R 2 = 0.48), a total of 103 network hub genes were identified, and 4 of them were hub nodes in the protein-protein interaction network as well. In validation, COL3A1 showed a higher correlation with the disease progression than any other hub genes in hub module in the test set (p < 0.001). Functional and pathway enrichment analysis demonstrated that COL3A1 is overrepresented in pathway of focal adhesion, which associated with tumor progression and might cause metastasis. Gene set enrichment analysis (GSEA) also demonstrated that the gene set of “MAPK signaling pathway” and focal adhesion related pathways were enriched in BCa samples with COL3A1 highly expressed (FDR < 0.05). Considering the clinicopathological parameters, highly-expressed COL3A1 was closely correlated with local recurrence and BCa stage. Survival analysis revealed that BCa patients with higher expression of COL3A1 had a significantly shorter overall survival time and disease free survival time.In conclusion, based on the co-expression analysis, COL3A1 was identified in the association with progression and prognosis of BCa, which might refer a poor prognosisprobably by regulating MAPK signaling pathway.