科研之友
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摘要
Purposes: TGF-beta pathway functions as both tumor-inhibitor and tumor-promoter in different phases of various cancers including bladder cancer. Our study was to determine if a TGF-beta pathway associated signature could distinguish more aggressive phenotype with worse survival outcomes. Methods: Gene expression profiling of 791 bladder cancer patients from both TCGA and GEO databases were selected and included in our study. 13-gene signature was generated by using Biometric Research Branch-Array Tools. With the specific risk score formula, patients in each dataset were classified into high risk or low risk group. The following analyses were performed in TCGA dataset and validated in other three independent testing sets (GSE13507, GSE31684 and GSE32548). Results: Patients in high risk group had significant shorter overall survival and disease specific survival, compared with who in low risk group. Multivariable Cox regression analysis revealed that the prognostic value of the 13-gene signature was independent of age, gender and smoking status. The 13-gene signature gave a significant performance in distinguishing patients at high risk of worse survival from those at low risk, as measured by the area under the receiver operating characteristic curve. Further analyses demonstrated that the risk score of this signature positively associated with stage and histologic grade (all P < 0.05). Conclusions: In present study, a novel TGF-beta pathway associated gene signature that is useful in survival prediction in bladder cancer patients was developed. The identification of high risk subpopulation could assist in selecting patients who need more aggressive therapeutic intervention. Meanwhile, the prognosis value of this signature and its potential as a biomarker deserve further investigation in future studies.
