Open AccessHigh expression of Krüppel‐like factor 5 is associated with poor prognosis in patients with colorectal cancer
Author(s) -
Takagi Yutaka,
Sakai Nozomu,
Yoshitomi Hideyuki,
Furukawa Katsunori,
Takayashiki Tsukasa,
Kuboki Satoshi,
Takano Shigetsugu,
Suzuki Daisuke,
Kagawa Shingo,
Mishima Takashi,
Nakadai Eri,
Miyauchi Hideaki,
Matsubara Hisahiro,
Ohtsuka Masayuki
Publication year - 2020
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14411
Subject(s) - colorectal cancer , metastasis , cancer research , medicine , cancer , ectopic expression , gene knockdown , oncology , immunohistochemistry , anoikis , biology , cell culture , genetics
Krüppel‐like factor 5 (KLF5) plays an oncogenic role and has diverse functions in cancer cells. However, correlation between KLF5 and clinical outcome has not been determined in patients with colorectal cancer and colorectal liver metastasis. Herein, we analyzed 65 patients with colorectal cancer who developed colorectal liver metastasis. Clinical effects were assessed through immunohistochemical analysis of primary colorectal cancer lesions and metastatic liver lesions. High expression of KLF5 in these tissues correlated with the presence of vascular invasion, elevated serum carbohydrate antigen 19‐9 levels, large diameters of metastatic liver tumors, and poor prognosis following surgery. Multivariate analyses revealed that high expression of KLF5 was an independent prognostic factor. Increased expression of KLF5 in both colorectal cancer primaries and colorectal liver metastasis was significantly associated with shorter overall survival time and time to surgical failure. Krüppel‐like factor 5 expression positively correlated with Ki‐67 and c‐Myc expression in colorectal cancer tissues. In vitro experiments with colon cancer cell lines showed that siRNA knockdown of KLF5 inhibited cell proliferation. Western blot analyses revealed that knockdown of KLF5 expression reduced cyclin D1 and c‐Myc expression. It also impaired the stem cell‐like properties of cancer cells in tumorsphere formation assays. Furthermore, anoikis assay indicated that KLF5 contributed to anoikis resistance. High KLF5 expression is associated with poor prognosis in patients with colorectal cancer and liver metastasis by promoting cell proliferation and cancer stem cell‐like properties.