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

• Published in: Gene expression 2010-01, Vol.14 (6), p.361-370
• Main Authors: LEVAN, KRISTINA, PARTHEEN, KAROLINA, ÖSTERBERG, LOVISA, OLSSON, BJÖRN, DELLE, ULLA, EKLIND, SASKIA, HORVATH, AND GYÖRGY
• Format: Article
• Language: English
• Subjects: adenocarcinoma; Adult; Aged; Aged, 80 and over; Arrays; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; breast; Cancer; Cancer therapies; Carcinoma, Endometrioid - genetics; Carcinoma, Endometrioid - metabolism; Carcinoma, Endometrioid - mortality; Cell and Molecular Biology; Cell- och molekylärbiologi; Classification; Cluster Analysis; Clustering; Endometrial Cancer; Endometrial Neoplasms - genetics; Endometrial Neoplasms - metabolism; Endometrial Neoplasms - mortality; Endometrium; estrogen; Estrogens; Expression Array; Female; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genes; Genomes; Genomics; Homogeneity; Humans; hybridization; hyperplasia; Malignancy; Medical prognosis; Middle Aged; Molecular biology; Natural sciences; Naturvetenskap; Neoplasm Staging; Oligonucleotide Array Sequence Analysis; pathway; Patients; profiles; Prognosis; Radiation therapy; Reproductive system; Reverse Transcriptase Polymerase Chain Reaction; Risk assessment; RNA, Messenger - genetics; Software; Statistical analysis; Subgroups; Survival; Survival Rate; Tumors; Uterine cancer; women
• ISSN: 1052-2166; 1555-3884; 1555-3884
• DOI: 10.3727/105221610X12735213181242

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.