High Cytoplasmic Expression of Krüppel-like Factor 4 Is an Independent Prognostic Factor of Better Survival in Hepatocellular Carcinoma

International Journal of Molecular Sciences

Hui-Ting Hsu⁵  Pei-Ru Wu⁵  Chih-Jung Chen⁵  Li-Sung Hsu²  Chung-Min Yeh⁵  Ming-Tai Hsing³  Yi-Shan Chiang¹  Ming-Tsung Lai⁴ 

[1] Biobank, Changhua Christian Hospital, Changhua 500, Taiwan; E-Mail:;Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung 402, Taiwan; E-Mail:;Department of Neurosurgery, Changhua Christian Hospital, Changhua 500, Taiwan; E-Mail:;Department of Pathology, Chung Shan Medical University, Taichung 500, Taiwan; E-Mail:;Department of Pathology, Chung Shan Medical University Hospital, Taichung 500, Taiwan

关键词: KLF4;    Ki-67;    hepatocellular carcinoma;    survival;    tissue microarray;    immunohistochemical study;   

DOI  :  10.3390/ijms15069894

来源: mdpi

【 摘 要 】

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality in the world. Hepatocarcinogenesis is complex, with an extraordinary molecular heterogeneity. Krüppel-like factor 4 (KLF4) plays an important role in cell proliferation and differentiation, and it can function as a tumor suppressor or an oncoprotein, depending on tissue type. The role of KLF4 in HCC remains controversial. The aim of this study was to explore the clinical significance of KLF4 expression in HCC. The study included 205 patients with surgical resection. We performed immunostaining for KLF4 and Ki-67 to investigate the correlations of the clinicopathological parameters of HCC and to examine the proliferative index. KLF4 staining was observed in the cytoplasm of non-tumorous hepatocytes and tumor cells. We subdivided the immunohistological staining results for KLF4 into low expression (Staining 0 and 1+) and high expression (Staining 2+ and 3+) subgroups. The expression of KLF4 was significantly correlated with tumor differentiation (p = 0.001). The Ki-67 proliferative index was significantly lower in well-differentiated HCCs (0.781% ± 1.02% vs. 2.16% ± 3.14%, p = 0.012), but not significantly different between low-KLF4 expression and high-KLF4 expression (1.87% ± 2.93% vs. 2.51% ± 3.28%, p = 0.32). Kaplan–Meier analysis showed that a high expression of KLF4 was significantly correlated with a longer disease-specific survival (p = 0.019). Univariate and multivariate analyses showed that high KLF4 expression was an independent predictor of a better disease-specific survival (p =0.017; hazard ratio = 0.398; 95% confidence interval: 0.19–0.85). High cytoplasmic expression of KLF4 was associated with better disease-specific survival and was an independently favorable prognostic factor in hepatocellular carcinoma. These promising results suggest that KLF4 may play an anti-oncogenic role in hepatocarcinogenesis.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.