RNA sequencing analysis reveals protective role of kruppel-like factor 3 in colorectal cancer
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Xiaohong Wang1,2,*, Zhonghua Jiang3,*, Yu Zhang2, Xiang Wang4, Li Liu4, Zhining Fan4
1Department of Digestive Endoscopy Center, Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
2Department of Gastroenterology, Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China
3Department of Gastroenterology, First People’s Hospital of Yancheng, Yancheng, Jiangsu Province, China
4Department of Digestive Endoscopy Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
*These authors have contributed equally to this work
Zhining Fan, email: [email protected]
Keywords: colorectal cancer, KLF3, survival analysis
Received: November 02, 2016 Accepted: January 27, 2017 Published: February 28, 2017
The Kruppel-like factor (KLF) family of transcription factors plays an important role in embryonic formation and cancer progression. This study was performed to determine the clinical importance of the KLF family in colorectal cancer (CRC). In total, 361 patients with CRC from The Cancer Genome Atlas (TCGA) cohort were used to comprehensively study the role of the KLF family in CRC. The results were then further validated using an in-house cohort (n=194). Univariate and multivariate Cox proportional hazards models were used to assess the risk factors for survival. In the TCGA cohort, KLF3 (hazard ratio [HR], 0.501; 95% confidence interval [CI], 0.272–0.920; P=0.025), KLF14 (HR, 1.454; 95% CI, 1.059–1.995; P=0.020), and KLF17 (HR, 1.241; 95% CI, 1.030–1.494, P=0.023) were identified as potential biomarkers in the univariate analysis, but after Cox proportional hazards analysis, only KLF3 (HR, 0.473; 95% CI, 0.230–0.831; P=0.012) was shown to be independently predictive of overall survival in patients with CRC. This finding was validated in our in-house cohort, which demonstrated that KLF3 expression was an independent predictor of both overall survival (HR, 0.628; 95% CI, 0.342–0.922; P=0.035) and disease-free survival (HR, 0.421; 95% CI, 0.317–0.697, P=0.016). KLF3 expression was inversely correlated with the N stage (P=0.015) and lymphovascular invasion (P=0.020). Collectively, loss of KLF3 was correlated with aggressive phenotypes and poor survival outcomes. KLF3 might be a potential new predictor and therapeutic target for CRC. Further study is needed for a more detailed understanding of the role of KLF3 in CRC.
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