The Krüppel-like factor (KLF5) as a predictive biomarker in preoperative chemoradiation therapy for rectal cancer

Abstract

Purpose: Preoperative chemoradiation therapy (CRT) has become the standard treatment for patients with locally advanced rectal cancer, 15%-30% of patients still progress while being treated with CRT. The aim of this study was to identify as important biomarker of poor response and evaluate the mechanism associated with CRT resistance.

Methods: This study included 60 human colon tumour pre-irradiation specimens. Expressions of epidermal growth factor receptor (EGFR), p53, Krüppel-like factor 5 (KLF5), C-ern, Ki67 were assessed and correlated with tumor regression grades and complete remission. We added in vitro study with biomarker which has been identified as important biomarker of poor response to evaluate the mechanism associated with CRT resistance.

Results: Pathologic complete remission (pCR) was achieved by 9 patients (18%). EGFR and KLF5 were significantly associated with pCR (P = 0.048, P = 0.023, respectfully). And multivariate analysis showed high KLF5 intensity was worse factor for pCR (P = 0.012). In vitro study, radiation or chemotherapy therapy stabilized KLF5 protein levels in a time- and dose-depended manner in HCT116 and Caco-2 cells. KLF5 overexpression in HCT116 stable cell line showed significantly better cell viability by increasing cyclinD1 and b-catenin compared to control cells in MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, suggesting that KLF5 mediates cell survival.

Conclusion: KLF5 was significantly associated with the presence of KRAS mutations, and KLF5 was an independent poor response predictor of CRT in rectal cancer. Our study is pilot study and more research will be needed in the future.