Abstract
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.