Gene expression of PMP22 is an independent prognostic factor for disease-free and overall survival in breast cancer patients

Dan Tong,Dietmar Pils,Andrea Wolf,Robert Zeillinger,Ingrid Schiebel,Christian F Singer,Nicole Concin,Margaretha Rudas,Georg Heinze,Gerda Hofstetter

doi:10.1186/1471-2407-10-682

Abstract

BackgroundGene expression of peripheral myelin protein 22 (PMP22) and the epithelial membrane proteins (EMPs) was found to be differentially expressed in invasive and non-invasive breast cell lines in a previous study. We want to evaluate the prognostic impact of the expression of these genes on breast cancer.MethodsIn a retrospective multicenter study, gene expression of PMP22 and the EMPs was measured in 249 primary breast tumors by real-time PCR. Results were statistically analyzed together with clinical data.ResultsIn univariable Cox regression analyses PMP22 and the EMPs were not associated with disease-free survival or tumor-related mortality. However, multivariable Cox regression revealed that patients with higher than median PMP22 gene expression have a 3.47 times higher risk to die of cancer compared to patients with equal values on clinical covariables but lower PMP22 expression. They also have a 1.77 times higher risk to relapse than those with lower PMP22 expression. The proportion of explained variation in overall survival due to PMP22 gene expression was 6.5% and thus PMP22 contributes equally to prognosis of overall survival as nodal status and estrogen receptor status. Cross validation demonstrates that 5-years survival rates can be refined by incorporating PMP22 into the prediction model.ConclusionsPMP22 gene expression is a novel independent prognostic factor for disease-free survival and overall survival for breast cancer patients. Including it into a model with established prognostic factors will increase the accuracy of prognosis.

Highlights

Gene expression of peripheral myelin protein 22 (PMP22) and the epithelial membrane proteins (EMPs) was found to be differentially expressed in invasive and non-invasive breast cell lines in a previous study
Patients with higher than median PMP22 gene expression had a 3.47 times higher risk to die of cancer than patients with lower than median PMP22 expression (Table 2)
Cross validation of the 5-year survival rates showed that the model including PMP22 expression has a broader range of prediction, a better discrimination of different risk groups than models excluding PMP22 expression

Summary

Introduction

Gene expression of peripheral myelin protein 22 (PMP22) and the epithelial membrane proteins (EMPs) was found to be differentially expressed in invasive and non-invasive breast cell lines in a previous study. We want to evaluate the prognostic impact of the expression of these genes on breast cancer. Breast cancer is by far the most frequent cancer of women with about one million new cases every year worldwide. Even though the prognosis for breast cancer patients is rather good, it is still the leading cause of cancer mortality in women causing about 400,000 annual deaths [1]. The most important prognostic factor is lymph node status, which indicates disease-free survival and overall survival in breast cancer. There is no predictive factor for chemotherapy that can be clinically used [2]. The prognosis of breast cancer is far from being precise. Identification of new prognostic and predictive markers will help patients to receive the proper treatment, it can provide new therapeutic targets

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