Int. J. Mol. Sci. 2014, 15(6), 9894-9906; doi:10.3390/ijms15069894
Article

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

1,2,3email, 1email, 1,3,4email, 5,6email, 1email, 7email, 8email, 9,10email and 1,3,* email
Received: 6 March 2014; in revised form: 26 May 2014 / Accepted: 26 May 2014 / Published: 3 June 2014
(This article belongs to the Section Molecular Pathology)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: 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.
Keywords: KLF4; Ki-67; hepatocellular carcinoma; survival; tissue microarray; immunohistochemical study
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MDPI and ACS Style

Hsu, H.-T.; Wu, P.-R.; Chen, C.-J.; Hsu, L.-S.; Yeh, C.-M.; Hsing, M.-T.; Chiang, Y.-S.; Lai, M.-T.; Yeh, K.-T. High Cytoplasmic Expression of Krüppel-like Factor 4 Is an Independent Prognostic Factor of Better Survival in Hepatocellular Carcinoma. Int. J. Mol. Sci. 2014, 15, 9894-9906.

AMA Style

Hsu H-T, Wu P-R, Chen C-J, Hsu L-S, Yeh C-M, Hsing M-T, Chiang Y-S, Lai M-T, Yeh K-T. High Cytoplasmic Expression of Krüppel-like Factor 4 Is an Independent Prognostic Factor of Better Survival in Hepatocellular Carcinoma. International Journal of Molecular Sciences. 2014; 15(6):9894-9906.

Chicago/Turabian Style

Hsu, Hui-Ting; Wu, Pei-Ru; Chen, Chih-Jung; Hsu, Li-Sung; Yeh, Chung-Min; Hsing, Ming-Tai; Chiang, Yi-Shan; Lai, Ming-Tsung; Yeh, Kun-Tu. 2014. "High Cytoplasmic Expression of Krüppel-like Factor 4 Is an Independent Prognostic Factor of Better Survival in Hepatocellular Carcinoma." Int. J. Mol. Sci. 15, no. 6: 9894-9906.

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