The prognostic effect of PTEN expression status in colorectal cancer development and evaluation of factors affecting it: miR-21 and promoter methylation.

Yaghoub Yazdani,Zeinab Zekavatian,Hossein Azadeh,Touraj Farazmandfar

doi:10.1186/s12929-016-0228-5

Abstract

BackgroundPTEN is a tumor suppressor gene which is involved in cellular proliferation, differentiation, and apoptosis. Loss or down-regulation of PTEN plays an important role in human cancers development. In this study, we investigated the effect of miR-21 and promoter methylation on the PTEN expression status in CRC tissues and analyzed association of the PTEN expression status with clinicopathological features in patients with CRC.ResultsThe PTEN expression was positively detected in 67.2 % CRC tissues and all adjacent non-cancerous samples. PTEN mRNA level was negatively correlated with miR-21 level (r = −0.595, P < 0.001). PTEN expression was also correlated directly with the PTEN mRNA level (r = 0.583, P < 0.001) and conversely with miR-21 level (r = −0.632, P < 0.001). PTEN Promoter methylation was significantly associated with PTEN expression status (p = 0.013). PTEN expression was negatively associated with tumor size (p = 0.007) and advanced tumor stage (P = 0.011). Multivariate analysis indicated that tumor stage, tumor differentiation and PTEN expression status were independent prognostic factors for overall carcinoma in CRC patients (P < 0.05). The Kaplan-Meier curve indicated a negative correlation between PTEN expression levels and survival of CRC patients (P = 0.013).ConclusionsThis study suggests a high frequency of miR-21 overexpression and aberrant promoter methylation in down-regulation of PTEN expression in colorectal carcinoma. Loss of PTEN may be a prognostic factor for patients with CRC.

Highlights

PTEN is a tumor suppressor gene which is involved in cellular proliferation, differentiation, and apoptosis
PTEN expression and factors affecting it in Colorectal cancer (CRC) Positive PTEN staining was detected in the nucleus of corresponding normal mucosa (Fig. 1a) or carcinoma cells (Fig. 1b)
PTEN expression in CRC tissues was statistically lower than the non-cancerous mucosa (P < 0.001) (Table 2)

Summary

Introduction

PTEN is a tumor suppressor gene which is involved in cellular proliferation, differentiation, and apoptosis. Despite great effort to PTEN (phosphatase and tensin homolog deletion on chromosome 10) is a tumor suppressor protein with the phosphatase activity and acts as a negative regulator in the PI3K/AKT pathways. This pathway control several processes related to cell metabolism, proliferation and survival. Apart from phosphatase activity, PTEN forms a nuclear complex with p53 protein, a tumor suppressor protein. This complex inhibits p53 decomposition and increases its transcriptional activity [5, 6].

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