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Combined Phosphatase and Tensin Homolog (PTEN) Loss and Fatty Acid Synthase (FAS) Overexpression Worsens the Prognosis of Chinese Patients with Hepatocellular Carcinoma
Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, Shanghai 200092, China
Department of Oncology, GlaxoSmithKline Research and Development Center, Shanghai 201203, China
Cancer Research, GlaxoSmithKline, Collegeville, PA 19426, USA
Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of CAS, Chinese Academy of Sciences, Shanghai 200031, China
These authors contributed equally to this work.
* Authors to whom correspondence should be addressed.
Received: 12 June 2012; in revised form: 26 July 2012 / Accepted: 1 August 2012 / Published: 10 August 2012
Abstract: We aimed to investigate the expression pattern of phosphatase and tensin homolog (PTEN), to evaluate the relationship between PTEN expression and clinicopathological characteristics, including fatty acid synthase (FAS) expression, and to determine the correlations of PTEN and FAS expression with survival in Chinese patients with hepatocellular carcinoma (HCC). The expression patterns of PTEN and FAS were determined using tissue microarrays and immunohistochemistry. The expression of PTEN was compared with the clinicopathological characteristics of HCC, including FAS expression. Receiver operator characteristic curves were used to calculate the clinical sensitivity and specificity of PTEN expression. Kaplan-Meier survival curves were constructed to evaluate the correlations of PTEN loss and FAS overexpression with overall survival. We found that the loss of PTEN expression occurred predominantly in the cytoplasm, while FAS was mainly localized to the cytoplasm. Cytoplasmic and total PTEN expression levels were significantly decreased in HCC compared with adjacent non-neoplastic tissue (both, p < 0.0001). Decreased cytoplasmic and total PTEN expression showed significant clinical sensitivity and specificity for HCC (both, p < 0.0001). Downregulation of PTEN in HCC relative to non-neoplastic tissue was significantly correlated with histological grade (p = 0.043 for histological grades I–II versus grade III). Loss of total PTEN was significantly correlated with FAS overexpression (p = 0.014). Loss of PTEN was also associated with poor prognosis of patients with poorly differentiated HCC (p = 0.049). Moreover, loss of PTEN combined with FAS overexpression was associated with significantly worse prognosis compared with other HCC cases (p = 0.011). Our data indicate that PTEN may serve as a potential diagnostic and prognostic marker of HCC. Upregulating PTEN expression and inhibiting FAS expression may offer a novel therapeutic approach for HCC.
Keywords: PTEN; FAS; prognosis; Chinese; hepatocellular carcinoma
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Zhu, X.; Qin, X.; Fei, M.; Hou, W.; Greshock, J.; Bachman, K.E.; Wooster, R.; Kang, J.; Qin, C.Y. Combined Phosphatase and Tensin Homolog (PTEN) Loss and Fatty Acid Synthase (FAS) Overexpression Worsens the Prognosis of Chinese Patients with Hepatocellular Carcinoma. Int. J. Mol. Sci. 2012, 13, 9980-9991.
Zhu X, Qin X, Fei M, Hou W, Greshock J, Bachman KE, Wooster R, Kang J, Qin CY. Combined Phosphatase and Tensin Homolog (PTEN) Loss and Fatty Acid Synthase (FAS) Overexpression Worsens the Prognosis of Chinese Patients with Hepatocellular Carcinoma. International Journal of Molecular Sciences. 2012; 13(8):9980-9991.
Zhu, Xuehua; Qin, Xia; Fei, Maogui; Hou, Wenmin; Greshock, Joel; Bachman, Kurtis E.; Wooster, Richard; Kang, Jiuhong; Qin, Crystal Ying. 2012. "Combined Phosphatase and Tensin Homolog (PTEN) Loss and Fatty Acid Synthase (FAS) Overexpression Worsens the Prognosis of Chinese Patients with Hepatocellular Carcinoma." Int. J. Mol. Sci. 13, no. 8: 9980-9991.