title: Combined phosphatase and tensin homolog (PTEN) loss and fatty acid synthase (FAS) overexpression worsens the prognosis of Chinese patients with hepatocellular carcinoma.
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.
authors.affiliation: Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Xuehua
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Oncology, GlaxoSmithKline Research and Development Center, Shanghai 201203, China.|Cancer Research, GlaxoSmithKline, Collegeville, PA 19426, USA.
authors.forename: Xia
authors.initials: X
authors.lastname: Qin
authors.affiliation: Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of CAS, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Maogui
authors.initials: M
authors.lastname: Fei
authors.affiliation: Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of CAS, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Wenmin
authors.initials: W
authors.lastname: Hou
authors.affiliation: Cancer Research, GlaxoSmithKline, Collegeville, PA 19426, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Greshock
authors.affiliation: Cancer Research, GlaxoSmithKline, Collegeville, PA 19426, USA.
authors.forename: Kurtis E
authors.initials: KE
authors.lastname: Bachman
authors.affiliation: Cancer Research, GlaxoSmithKline, Collegeville, PA 19426, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Wooster
authors.affiliation: Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Jiuhong
authors.initials: J
authors.lastname: Kang
authors.affiliation: Department of Oncology, GlaxoSmithKline Research and Development Center, Shanghai 201203, China.|Cancer Research, GlaxoSmithKline, Collegeville, PA 19426, USA.
authors.forename: Crystal Ying
authors.initials: CY
authors.lastname: Qin
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D002681:China; D054890:Fatty Acid Synthase, Type I / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D011379:Prognosis; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; C518729:FASN protein, human; D054890:Fatty Acid Synthase, Type I; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human