The tumor suppressor role of Src homology phosphotyrosine phosphatase 2 in hepatocellular carcinoma.
OBJECTIVE
The human gene PTPN11, which encodes the non-receptor protein tyrosine phosphatase of Src homology phosphotyrosine phosphatase 2 (Shp2), has been previously well interpreted as a proto-oncogene in a variety of malignancies. However, the tumor suppressor role of Shp2 has also been reported. The present study was conducted to investigate the role of Shp2 expression and its associated clinical manifestations in hepatocellular carcinoma (HCC).


METHODS
A tissue microarray of 333 pairs of HCC and self-matched adjacent non-tumor tissues was constructed, and the expression of Shp2 was determined by immunohistochemistry. The results were also conformed by Western blotting and quantitative PCR of 31 self-paired fresh HCC specimens. The associations of Shp2 expression with 25 clinicopathologic features were analyzed. Overall survival analysis and multivariate analysis were performed.


RESULTS
Significantly decreased Shp2 expression in tumor tissues (T) compared with adjacent non-tumor tissues (NT) could be detected, and the positive rate was 66.1 and 96.7%, respectively. We combined the T and NT Shp2 immunoreactivity by a variable of the decrease in Shp2 expression (ΔShp2) and divided cases into 2 groups: T < NT and T ≥ NT. Survival analysis showed both low Shp2 expression and T < NT group were significantly associated with short overall survival. Multivariate analysis showed ΔShp2 was an independent prognostic marker (P = 0.033; HR: 0.527; 95% CI: 0.293-0.950).


CONCLUSIONS
Shp2 is a tumor suppressor, and the decrease in Shp2 expression was a new prognostic marker in HCC. The oncogenic role of Shp2 was tissue specific, and the therapeutic target of human gene PTPN11 should be reconsidered.
Pathology Department, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China.
Chengying
C
Jiang
Fangke
F
Hu
Yanhong
Y
Tai
Jingli
J
Du
Beibei
B
Mao
Zengqiang
Z
Yuan
Yan
Y
Wang
Lixin
L
Wei
D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D046228:Microarray Analysis / Q000706:statistics & numerical data; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000235:genetics / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D014408:Biomarkers, Tumor; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D025521:Tumor Suppressor Proteins; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11