| Background and AimColorectal cancer is very common worldwide and among cancers with highest incidence globally. As the aggravation of mental stress and improvement of quality of life and changes of dietary patterns due to the bloom of economy, and environmental deterioration, the incidence of colorectal cancer in China is increasingly rising. For colorectal cancer, surgical resection remains the only potentially curative therapy.However, due to the high malignant potential of colorectal cancer, they are usually diagnosed at an advanced stage and often recur even after curative surgical excision.Therefore, it is clinically imperative to clarify the mechanisms of colorectal carcinogenesis and to identify biomarkers that predict recurrence and progression of the disease that contribute to novel strategies or treatments to colorectal cancer.PTEN is the most valuable tumor suppressor gene after p53 was identified and it is found to be involved in regulation of a variety of signaling pathways. Quite a few studies have detected depletion or inactivation of PTEN in numerous tumors, due to genetic or epigenetic changes, namely mutation, loss of heterozygosity, promoter hypermethylation et al.. Furthermore, PTEN could be modified by phosphorylation,posphorylated-PTEN lost tumor suppressor function and in turn leaded to increased cancer susceptibility. Deletion or mutation of PTEN was also frequently found in colorectal cancer, indicating that PTEN might involve in the colorectal carcinogenesis.Despite many studies have investigated the PTEN expression and its association with biological behaviors or prognosis of colorectal cancer, however, the findings was inconsistent. Additionally, the expression pattern of phosphorylated status of PTEN in colorectal carcinogenesis and their clinical significance with colorectal cancer has never been reported. Thus, we detect PTEN and p-PTEN expression in different intestinal mucosa lesions to obtain a more comprehensive estimate of the putative influence of PTEN and p-PTEN expression on colorectal cancer. Moreover, we conducted a meta-analysis of relevant studies on PTEN and colorectal cancer, on the one hand to solve controversy, on the other hand to guide our clinical study.Methods:1. A total of 306 cases of specimen were from endoscope biopsy or surgical operation in the first affiliated hospital of Nanchang University during Jan 2007 to Jun 2009, including 60 cases of colorectal adenomas and 246 cases of colorectal cancer tissue samples, their pathological diagnosis refered to the WHO criteria. Sixty normal mucosa samples taken from gastrointestinal endoscope biopsy were embedded into paraffin blocks during May 2014 to September 2014. The protein expression of PTEN and p-PTEN were examined on the paraffin sections by two-step immunohistochemical method. SPSS19.0 was used for statistical analysis.2. A systematic search of Pub Med, EMBASE and CBMdisc was performed to identify potentially relevant publications involved in the expression of PTEN and its associations with clinicopathological parameters and prognosis. Meta-anslysis was performed by Stata14.0.Results:1. Expression of PTEN and p-PTEN in colorectal carcinogenesis and the association with clinicopathological characteristics of colorectal adenoma(1) PTEN expression gradually decrease with the progress of colorectal carcinogenesis, with the lowest expression in cancer group, the overall difference is significantly different(p<0.001), however, the difference is not statistically significant between colorectal adenoma and cancer group(p=0.777);(2) p-PTEN expression gradually increase with the progress of colorectal carcinogenesis, with the highest expression in cancer group, the overall difference is significantly different(p<0.001), however, the difference is not statistically significant between colorectal adenoma and cancer group(p=0.324);(3) Both the expression of PTEN and p-PTEN were not associated with the clinicopathological characteristics of colorectal adenoma(p>0.05).2. PTEN and p-PTEN the relationship between PTEN and colorectal cancer clinical pathological parameters(1) The expression of PTEN was statistically negatively related with lymphatic metastasis(p=0.041), not significantly related with other clinicopathological parameters(p>0.05);(2) The expression of p-PTEN was statistically positively correlated with the degree of tumor differentiation, lymphatic metastasis, distant metastasis and TNM stage(p<0.001, p<0.001, p<0.001, p=0.022), not significantly related with other clinicopathological parameters(p>0.05);(3) There was no significant correlation between the expression of PTEN and p-PTEN(p>0.05).3. Eighteen studies involving approximately 4000 participants were included in the final analysis. Results of Meta-analysis showed that:(1) There were significant differences in positive rate of PTEN expression between colorectal cancer tissues and normal tissues(OR=0.17, 95%CI=0.07-0.40,p=0.001), however, the difference was not statistically significant between colorectal cancer and adenoma tissues(OR=0.81, 95%CI=0.10-6.31, p=0.841);(2) PTEN expression was associated with tumor size(OR=1.47, 95%CI=1.12-1.91, p=0.687), vascular invasion(OR=0.87, 95%CI=0.77-0.98, p=0.680), and tumor stage(OR=1.51, 95%CI=1.06-2.14, p=0.026), but not associated with sex, age,tumor location, differentiation, lymphatic invasion et al.(p>0.05);(3) Loss of PTEN was associated with unfavorable overall survival(HR=0.60,95%CI=0.37-0.82; I2=69.2%, p=0.059) instead of relapse free survival(HR=1.04,95%CI=0.64-1.44;I2=62.7%,p=0.045).Conclusions:1. Reduced expression of PTEN and increased PTEN phosphorylation might jointly contribute to colorectal carcinogenesis, however, the expression of PTEN and p-PTEN do not correlated with each other.2. Reduced PTEN expression may be an independent risk factor for poor overall survial of patients with colorectal cancer, more studies are now needed to further clarify the prognostic value of p-PTEN in colorectal cancer. |
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