title: Target-based molecular signature characteristics of cervical adenocarcinoma and squamous cell carcinoma.
abstract: There is an urgent need for molecular marker studies of adenocarcinoma (AC) and squamous cell carcinoma (SCC) of the uterine cervix. This study utilized oligomicroarray and pathway analyses to characterize a transcriptomic signature with molecular networks associated with AC and SCC. A 10K oligomicroarray was used to identify potential transcripts that were differentially expressed in cervical cancers from 28 patients and common reference RNAs from 17 different normal cervixes. Molecular networks were correlated using genomics tools to globally explore cellular pathways. Gene expression levels of 46 transcripts separated cancer samples into AC and SCC groups. Genes including: KRT17, IGFBP2, CALCA and VIPR1 were differentially expressed in AC and SCC. In addition, we identified a transcriptomic signature that predicted tumor classification and progression based upon its cellular processes. The downregulated signatures for SCC were cell death of pheochromocytoma cells (P=0.0037), apoptosis of neurons (P=0.009) and damage to DNA (P=0.0038). By contrast, the upregulated molecular signatures in AC were immunological disorder (P=0.006), splenomegaly (P=0.0053) and hepatic system disorder (P=0.006). The G2/M DNA damage checkpoint regulation pathway (P=0.05) was found to be significantly linked to IGF1R as a new regulatory component of a putative cytoplasmic signaling cascade in SCC. By contrast, the antigen presenting canonical pathway (P=0.038) appeared to be linked to PPARγ in AC. Taken together, these experiments provide important new information regarding the role of molecular networks in mediating SCC and AC, possibly through two independent pathways, and contribute to provide new targets for the prevention and treatment of cervical cancer.
authors.affiliation: Catholic Research Institutes of Medical Science, Catholic University of Korea, Incheon St. Mary's Hospital, Incheon, Republic of Korea.
authors.forename: Yong-Wan
authors.initials: YW
authors.lastname: Kim
authors.forename: Su Mi
authors.initials: SM
authors.lastname: Bae
authors.forename: Yong Wook
authors.initials: YW
authors.lastname: Kim
authors.forename: Dong Choon
authors.initials: DC
authors.lastname: Park
authors.forename: Keun-Ho
authors.initials: KH
authors.lastname: Lee
authors.forename: Hai-Bo
authors.initials: HB
authors.lastname: Liu
authors.forename: In-Wook
authors.initials: IW
authors.lastname: Kim
authors.forename: Chun Keun
authors.initials: CK
authors.lastname: Jang
authors.forename: Woong Shick
authors.initials: WS
authors.lastname: Ahn
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D002116:Calcitonin / Q000235:genetics; D015740:Calcitonin Gene-Related Peptide; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D015536:Down-Regulation; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000235:genetics; D053537:Keratin-17 / Q000235:genetics; D047495:PPAR gamma / Q000235:genetics; D011498:Protein Precursors / Q000235:genetics; D017526:Receptor, IGF Type 1 / Q000235:genetics; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C000606589:CALCA protein, human; D018971:Insulin-Like Growth Factor Binding Protein 2; D053537:Keratin-17; D047495:PPAR gamma; D011498:Protein Precursors; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; C495506:VIPR1 protein, human; D002116:Calcitonin; D017526:Receptor, IGF Type 1; D015740:Calcitonin Gene-Related Peptide