Protein phosphatase-2A is down-regulated in patients within clear cell renal cell carcinoma.
BACKGROUND
Protein phosphatase-2A (PP2A) is one of the major cellular serine-threonine phosphatases. It positively regulates apoptosis and negatively regulates the mitogenic pathway, suggesting that loss of it might be involved in cancer development. Recent studies found its association with breast, lung and colorectal cancer; however, its expression profile and its prognostic value in clear cell renal cell carcinoma (ccRCC) have not been investigated.


METHODS
Real-time quantitative PCR (qRT-PCR) and Western blot were used to explore PP2A expression in ccRCC and normal renal tissues. Moreover immunohistochemistry (ICH) was used to detect the expression of PP2A in ccRCC. Spearman's rank correlation, Kaplan-Meier plots and Cox proportional hazards regression model were used to analyze the data.


RESULTS
Down-regulated expression of PP2A mRNA and protein was observed in the majority of ccRCC by qRT-PCR and Western blot when compared with their paired normal renal tissues. Clinic pathological analysis was showed a significant correlation existed between the lower expression of PP2A protein with the histological grade, lymph node metastasis and tumor distant metastasis (P<0.05); Survival analysis by Kaplan-Meier survival curve and log-rank test demonstrated that reduced PP2A expression in cancer tissue predicted poorer overall survival (OS) compared with group in higher expression. Notably, multivariate analyses by Cox's proportional hazard model revealed that expression of PP2A was an independent prognostic factor in ccRCC.


CONCLUSIONS
These results suggest that the aberrant expression of PP2A in human ccRCC is possibly involved with tumorigenesis and development, and the PP2A protein could act as a potential biomarker for prognosis assessment of renal cancer. Further studies on the cellular functions of PP2A need to address these issues.
Department of Urology, Pudong New Area People's Hospital Shanghai, 201200, China ; Department of Urology, Shanghai Tenth People's Hospital, Tongji University Shanghai, 200072, China.
Jun
J
Li
Department of Urology, Pudong New Area People's Hospital Shanghai, 201200, China.
Chang
C
Sheng
Department of Urology, Shanghai Tenth People's Hospital, Tongji University Shanghai, 200072, China.
Wei
W
Li
Department of Urology, Shanghai Tenth People's Hospital, Tongji University Shanghai, 200072, China.
Jun-Hua
JH
Zheng
D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000201:enzymology* / Q000401:mortality; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000201:enzymology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D054648:Protein Phosphatase 2 / Q000032:analysis / Q000096:biosynthesis*; D060888:Real-Time Polymerase Chain Reaction
D014408:Biomarkers, Tumor; C517189:PPP2CA protein, human; D054648:Protein Phosphatase 2
PP2A; Phosphatase-2A; biomarker; clear cell renal cell carcinoma; prognosis; serine-threonine phosphatases