Loss of PTEN expression in breast cancer: association with clinicopathological characteristics and prognosis.

Shuting Li,Jin Yang,Mengying Wang,Zheling Chen,Pan Li,Meng Lv,Yanwei Shen,Jiao Yang

doi:10.18632/oncotarget.16761

Shuting Li, Jin Yang + Show 6 more

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https://doi.org/10.18632/oncotarget.16761

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Abstract

Various studies have evaluated the significance of PTEN (phosphatase and tensin homolog deleted from chromosome 10) expression in breast cancer, but their results remain controversial. We conducted a meta-analysis to evaluate the associations of PTEN expression with clinicopathological characteristics and prognosis in breast cancer. PubMed, Embase, Web of Science, and China National Knowledge Infrastructure were searched to identify relevant publications. The associations between PTEN expression and clinicopathological parameters, disease-free survival (DFS), and overall survival (OS) were then assessed via meta-analyses of odds ratio (ORs) and hazard ratio (HRs) with 95% confidence intervals (CIs). Based on 27 studies involving 10,231 patients, the pooled results revealed that PTEN loss was significantly more common in breast cancer than in normal tissues (OR = 12.15, 95% CI = 6.48–22.79, P < 0.00001) and that PTEN loss had clear associations with larger tumor size (> 2 cm, OR = 0.62, 95% CI = 0.48–0.82, P = 0.0006), lymph node metastasis(OR = 0.61, 95% CI = 0.45–0.82, P = 0.0001), later TNM stage(stage III–IV, OR = 0.55, 95% CI = 0.35–0.86, P = 0.009), poor differentiation(OR = 0.37, 95% CI = 0.24–0.59, P < 0.0001), and the highly aggressive triple-negative phenotype (OR = 1.62, 95% CI = 1.23–2.12, P = 0.0005). Moreover, patients with PTEN loss exhibited significantly worse DFS and OS(HR = 1.63, 95% CI = 1.04–2.22, P < 0.00001; HR = 1.41, 95% CI = 1.08–1.73, P < 0.0001; respectively). In conclusion, PTEN loss might predict more aggressive behavior and worse outcomes in patients with breast cancer.

Highlights

Breast cancer is the most common malignancy among women in both developing and developed countries, accounting for about one fifth of new cancer cases in women [1]
We evaluated the associations between PTEN loss and the survival outcomes of breast cancer patients
Several metaanalyses have demonstrated that various biomarkers may be associated with the survival of patients with breast cancer, including p27 [35], vascular endothelial growth factor (VEGF) [36], Cyclooxygenase (COX-2) [37], B cell lymphoma 2 protein (BCL-2) [38], and cyclin D1 [39]

Summary

Introduction

Breast cancer is the most common malignancy among women in both developing and developed countries, accounting for about one fifth of new cancer cases in women [1]. Breast cancer still remains the leading cause of death in women worldwide [2]. It is important to identify potential biomarkers that could be used to screen high-risk patients and predict breast cancer prognosis in conjunction with classical pathological parameters. PTEN dephosphorylates the 3′ end of the triphosphate PIP3 in the inositol ring, resulting in the biphosphate PIP2, which inhibits AKT activation and downstream signaling processes that depend on AKT for activation. Inactivation of PTEN, and lack of inhibition of the AKT-dependent processes, has been associated with tumorigenesis in multiple human cancers, including breast cancer [4]

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