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

Lushun Yuan,Liang Chen,Kaiyu Qian,Xinyue Cao,Conghua Xie,Guofeng Qian,Xinghuan Wang,Bo Shu,Yongzhi Wang,Yu Xiao,Yuan Zhu

doi:10.18632/oncotarget.19733

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 (R2 = 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.

Highlights

Bladder cancer is one of the worldwide cancers in men and women populations
Survival analysis revealed that bladder cancer (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
We found that the module eigengene (ME) in the blue module showed a higher correlation with RC_Stage than other modules (Figure 3B)

Summary

Introduction

Bladder cancer is one of the worldwide cancers in men and women populations. The risk factors are different, including tobacco use, Schistosoma infection, chemical exposure, diet and lifestyle trends, atmospheric pollution and genetic susceptibilities, so the incidence of bladder cancer has a considerable global variation [1, 2]. In China, bladder cancer is reported to be the most common genitourinary malignancy, and its incidence has increased rapidly in the last few decades [4]. It has been reported that 30 - 70% of those tumors have a chance of recurrence, and up to 30% of the population quickly progress to muscle-invasive disease [6]. Bladder cancer could be characterized by 2 histological subtypes: non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) [7]. 10% to 30% of patients with NMIBC recur and progress to MIBC, which is responsible for most bladder cancerspecific deaths [8]. As MIBC frequently causes distant metastases, it is urgent to understand the mechanisms that promote cancer progression and find novel molecular markers for the early diagnosis and prognosis

Methods

Results

Conclusion