Abstract
The tumor suppressor phosphatase and tensin homolog (PTEN) is an important negative regulator of cell-survival signaling. However, available results for the prognostic value of PTEN expression in patients with cancer remain controversial. Therefore, a meta-analysis of published studies investigating this issue was performed. A literature search via PubMed and EMBASE databases was conducted. Statistical analysis was performed by using the STATA 12.0 (STATA Corp., College, TX). Data from eligible studies were extracted and included into the meta-analysis using a random effects model. A total of 3,810 patients from 27 studies were included in the meta-analysis, 22 investigating the relationship between PTEN expression and overall survival (OS) using univariate analysis, and nine with multivariate analysis. The pooled hazard ratio (HR) for OS was 1.64 (95% confidence interval (CI): 1.32-2.05) by univariate analysis and 1.56 (95% CI: 1.20-2.03) by multivariate analysis. In addition, eight papers including two disease-free-survival analyses (DFSs), four relapse-free-survival analyses (RFSs), three progression-free-survival analyses (PFSs) and one metastasis-free-survival analysis (MFS) reported the effect of PTEN on survival. The results showed that loss of PTEN expression was significant correlated with poor prognosis, with a combined HR of 1.74 (95% CI: 1.24-2.44). Furthermore, in the stratified analysis by the year of publication, ethnicity, cancer type, method, cut- off value, median follow-up time and neoadjuvant therapy in which the study was conducted, we found that the ethnicity, cancer type, method, median follow-up time and neoadjuvant therapy are associated with prognosis. Our study shows that negative or loss of expression of PTEN is associated with worse prognosis in patients with cancer. However, adequately designed prospective studies need to be performed for confirmation.
Highlights
The global burden of cancer continues to increase dramatically with approximately 12.7 million new cancer cases and 7.6 million cancer-related deaths every year worldwide (Jemal et al, 2011)
The results showed that loss of phosphatase and tensin homolog (PTEN) expression was significant correlated with poor prognosis, with a combined hazard ratio (HR) of 1.74
After the abstracts met these conditions, the full texts were analyzed and included into our meta-analysis according to the following criteria: i) articles were written as full paper; ii) expression levels of PTEN were compared to patient’s overall survival (OS) or other survival analysis; iii) expression of the proteins were evaluated in tumor tissues by immunohistochemistry (IHC) or reverse transcription and polymerase chain reaction (RT-PCR) analysis; iv) Hazard ratios (HR) and 95%CI for survival were provided or could be calculated from the sufficient data; v) if the same group of patients were used to analyze more than once, the most complete research was selected for our study
Summary
The global burden of cancer continues to increase dramatically with approximately 12.7 million new cancer cases and 7.6 million cancer-related deaths every year worldwide (Jemal et al, 2011). Investigate the relationship between the expression of PTEN and the prognosis of patients with cancers is important, as this will be helpful for adopting appropriate targeted therapy. Results: A total of 3,810 patients from 27 studies were included in the meta-analysis, 22 investigating the relationship between PTEN expression and overall survival (OS) using univariate analysis, and nine with multivariate analysis. In the stratified analysis by the year of publication, ethnicity, cancer type, method, cutoff value, median follow-up time and neoadjuvant therapy in which the study was conducted, we found that the ethnicity, cancer type, method, median follow-up time and neoadjuvant therapy are associated with prognosis. Conclusions: Our study shows that negative or loss of expression of PTEN is associated with worse prognosis in patients with cancer. Adequately designed prospective studies need to be performed for confirmation
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