Searching for pathogenic gene functions to cervical cancer

Objective. Molecular pathology of cervical cancers associated with human papillomavirus (HPV) infection is presently unclear. In an effort to clarify this issue, we investigated gene expression profiles and pathogenic cellular processes of cervical cancer lesions. Methods. Tissues of 11 patients (invasive cancer stages lb - IIIa) were investigated by a cDNA microarray of 4700 genes, hierarchical clustering and the Gene Ontology (GO). Results. We identified 74 genes showing a more than 2-fold difference in their expression in at least 8 out of 11 patients. Among these, 33 genes were up-regulated, in contrast, 41 genes were down-regulated. The gene expression profiles were classified into mutually dependent 345 function sets, resulting in 611 cellular processes according to the GO. The GO analysis showed that cervical carcinogenesis underwent complete down-regulation of cell death, protein biosynthesis, and nucleic acid metabolism. Also, genes belonging to nucleic acid binding and structural molecule activity were significantly down-regulated. In contrast, significant up-regulation was shown in skeletal development, immune response, and extracellular activity. Conclusion. These data suggest that the regulated genes and cellular processes could be further used for predicting prognosis and diagnosis of cervical cancer patients, and further investigation and functional characterization of the identified genes is warranted. (C) 2004 Elsevier Inc. All rights reserved.