J Cancer 2020; 11(7):1768-1779. doi:10.7150/jca.38741 This issue

Research Paper

Construction and validation of an eight-gene signature with great prognostic value in bladder cancer

Xin Yan1,2, Xun Fu1, Zi-Xin Guo1, Xiao-Ping Liu1, Tong-Zu Liu1, Sheng Li1,2,3✉

1. Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
2. Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
3. Human Genetics Resource Preservation Center of Hubei Province, Wuhan 430071, China.

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Citation:
Yan X, Fu X, Guo ZX, Liu XP, Liu TZ, Li S. Construction and validation of an eight-gene signature with great prognostic value in bladder cancer. J Cancer 2020; 11(7):1768-1779. doi:10.7150/jca.38741. Available from https://www.jcancer.org/v11p1768.htm

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Abstract

Bladder cancer (BC) is one of the most common malignancies in urinary system with a common malignancy in urinary system with a high mortality and recurrence rate, so we attempt to construct a gene signature to predict the prognosis of BCs. We initially established a co-expression network by performing WGCNA analysis and further identified magenta module as key module (P = 8e-05, R2 = 0.4). Subsequently, we screened 12 genes associated with survival from the key module, which were selected to construct an eight-gene signature by establishing a LASSO Cox model. Moreover, we reckoned the risk score (RS) of each sample, through which we could divide samples into two groups (the high-risk and low-risk groups) and verify the signature, in the training set and 3 validation sets (internal test set, GSE13507and E-MTAB-4321). This signature could distinguish between the high- and low- risk patients well (survival analysis: P = 0.015; AUC: 0.61 at 1 year, 0.61 at 3 years and 0.61 at 5 years). In the validation sets, this signature also showed good performance, which was consistent with the training test. Furthermore, we plotted a nomogram to predict the possibility of the overall survival (OS) and three calibration curves to predict the effectiveness of the nomogram, which suggested good value and clinical utility of the nomogram. In conclusion, we established an eight-gene signature, which was probably effective in the prediction of prognosis of patients with BC.

Keywords: bladder cancer, LASSO, WGCNA, grade, survival, gene signature, nomogram, overall survival, prognosis