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

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

Abstract

Background: 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.

Methods: In 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.

Results: In 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.

Conclusions: PMP22 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.

Figures

Figure 1
Figure 1
Kaplan-Meier curves comparing patients with high and low PMP22 gene expression (dichotomized at the median). 1A. DFS, not adjusted; 1B. OS, not adjusted; 1C. DFS, adjusted survival function from Cox model (comparing high and low PMP22 gene expression for patients with average values for T, pN, G, and ER); 1 D. OS, adjusted survivor function from Cox model (comparing high and low PMP22 gene expression for patients with average values for T, pN, G, ER, and age).

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