RRC ID 69602
Author Imadome K, Iwakawa M, Nakawatari M, Fujita H, Kato S, Ohno T, Nakamura E, Ohkubo Y, Tamaki T, Kiyohara H, Imai T.
Title Subtypes of cervical adenosquamous carcinomas classified by EpCAM expression related to radiosensitivity.
Journal Cancer Biol Ther
Abstract Adenosquamous carcinoma (ASC) is a relatively uncommon histological subtype of cervical cancer (CC). A point of controversy is the relative prognosis of ASC compared to squamous cell carcinoma (SCC). We hypothesized that ASC could be classified into two intrinsic molecular subtypes with different outcomes. We examined 143 biopsy samples of CC patients to identify a molecule for classification using microarray expression analysis and immunohistochemical analysis (IHA). We found specific expression profiles of candidate genes that distinguished two clusters. All adenocarcinoma (AC) patients were classified into one cluster, and most SCC patients fell into the other cluster. ASC patients were classified across the two clusters, which showed significantly different prognoses. The SCC-like expression signature comprised ANXA8, CK5, IFI16, and nectin-1; and the AC-like signature comprised EpCAM, and TMEM98. These signature-specific genes hypothetically indicated specific pathways by ontological analysis. The AC-like signature suggested an epithelial-mesenchymal transition and activated β-catenin pathway, while the SCC-like signature suggested keratinocyte differentiation, HPV infection, and p53-mediated apoptosis. IHA revealed that positive expression of the most promising protein, EpCAM, was significantly associated with poor prognosis. In addition, the inhibition of EpCAM expression using siRNA significantly increased radiation-induced cell death in the cervical cell line, ME-180. In conclusion, we identified two possible ASC subtypes associated with different expression profiles and different prognoses. This work provides a novel set of genes that could be used as independent prognostic markers and therapy targets.
Volume 10(10)
Pages 1019-26
Published 2010-11-15
DOI 10.4161/cbt.10.10.13249
PII 13249
PMID 20855955
MeSH Adenocarcinoma / classification* Adenocarcinoma / metabolism Adenocarcinoma / pathology Antigens, Neoplasm / genetics Antigens, Neoplasm / metabolism* Biomarkers, Tumor / genetics Biomarkers, Tumor / metabolism* Blotting, Western Carcinoma, Adenosquamous / classification* Carcinoma, Adenosquamous / metabolism Carcinoma, Adenosquamous / pathology Carcinoma, Squamous Cell / classification* Carcinoma, Squamous Cell / metabolism Carcinoma, Squamous Cell / pathology Cell Adhesion Molecules / antagonists & inhibitors Cell Adhesion Molecules / genetics Cell Adhesion Molecules / metabolism* Epithelial Cell Adhesion Molecule Female Gene Expression Profiling Humans Immunoenzyme Techniques Oligonucleotide Array Sequence Analysis Prognosis RNA, Messenger / genetics RNA, Small Interfering / genetics Radiation Tolerance / genetics* Reverse Transcriptase Polymerase Chain Reaction Uterine Cervical Neoplasms / classification* Uterine Cervical Neoplasms / metabolism Uterine Cervical Neoplasms / pathology
IF 3.659
Human and Animal Cells ME-180(RCB2106)