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Genetic alterations and expression of PTEN and its relationship with cancer stem cell markers to investigate pathogenesis and to evaluate prognosis in hepatocellular carcinoma
  1. Dingbao Chen1,
  2. Zhao Li2,
  3. Qian Cheng2,
  4. Ying Wang,
  5. Lihua Qian,
  6. Jie Gao2,
  7. Ji-Ye Zhu2
  1. 1 Pathology,Hepatobiliary Surgery, Peking Uni­versity People's Hospital, Beijing, China
  2. 2 Hepatobiliary Surgery, Peking University People's Hospital, Beijing, China
  1. Correspondence to Dr Ji-Ye Zhu, Hepatobiliary Surgery, Peking University People's Hospital, Beijing, China; gandanwk{at}


Aims To investigate molecular alteration and expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in hepatocellular carcinoma (HCC), and to evaluate the correlation between PTEN and cancer stem cell (CSC) markers and the prognostic value of these markers.

Methods We evaluated changes of PTEN and CSC markers (CD133, epithelial cell adhesion molecule (EpCAM) and CK19) in 183 resection specimens by immunohistochemistry (IHC) and detected PTEN and phosphoinositide-3-kinase catalytic-alpha (PIK3CA) gene by fluorescence in situ hybridisation (FISH) in some specimens.

Results PTEN and CD133, EpCAM and CK19 in 183 resection specimens were studied by IHC, and PTEN and PIK3CA genes were detected by FISH. PTEN expression was reduced in 92 HCC tissues (50.3%). There were 16 HCCs with PTEN deletion (51.6%). Comparison between PTEN IHC and FISH showed that the analysis was highly concordant (54/59, 91.5%). There were 19 HCCs with PIK3CA amplification. Deletion of PTEN was positively correlated with amplification of PIK3CA. Positive expression of CD133, EpCAM and CK19 was correlated with steatosis, moderate to poor differentiation, and so on. Reduction of PTEN expression was negatively correlated with positive expression of CD133, EpCAM and CK19. Reduced expression of PTEN (p=0.028) was an independent predictor for HCC recurrence and overall survival in HCC. PTEN−/CD133+ group had shorter OS and RFS time.

Conclusions PTEN plays a key role in hepatocarcinogenesis and reduction of PTEN expression is related to increased expression of CD133, EpCAM and CK19, which is a useful tool to evaluate HCC prognosis and recurrence.

  • hepatocellular carcinoma
  • PTEN
  • PIK3CA
  • cancer stem cells
  • pathogenesis

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  • DC and ZL are joint first authors.

  • Handling editor Runjan Chetty.

  • Correction notice This article has been corrected since it was published Online First. Under the

    Results heading, "PTEN expression was reduced in 91 HCC tissues (49.7%)" has been changed to "PTEN expression was reduced in 92 HCC tissues (50.3%)".

  • Funding This study is supported by grants from the National Natural Science Foundation of China (81502509 and 81502581).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval The study was approved by the Institutional Review Board at Peking University People’s Hospital.

  • Provenance and peer review Not commissioned; internally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.