Identification of a Gene Expression Signature for Survival Prediction in Type I Endometrial Carcinoma

Abstract

Endometrial cancer is the most common malignancy of the female reproductive tract. In many cases the prognosis is favorable, but 22% of affected women die from the disease. We aimed to study potential differences in gene expression between endometrioid adenocarcinomas from survivors (5-year survival) and nonsurvivors. Forty-five patients were included in the investigation, of which 21 were survivors and 24 were nonsurvivors. The tumors were analyzed with genome-wide expression array analysis, represented by 13,526 genes. Distinct differences in gene expression were found between the groups. A t-test established that 218 genes were significantly differentially expressed (p < 0.001) between the two survival groups, and in a cross-validation test 40 of the 45 (89%) tumors were classified correctly. The 218 differentially expressed genes were subjected to hierachical clustering analysis, which yielded two clusters both exhibiting over 80% homogeneity with respect to survival. When the additional constraint of fold change (FC > 2) was added the hierachical clustering yielded similar results. Stage I tumors are expected to have a favorable prognosis. However, in our tumor material there were six nonsurvivors with stage I tumors. Five out of six stage I nonsurvivors clustered in the nonsurvival fraction. Our findings suggest that a subgroup of early stage endometroid adenocarcinomas can be correctly classified as potentially aggressive by using molecular biology in combination with conventional markers, thereby providing a tool for a more accurate classification and risk evaluation of the individual patient.