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Identification of genes with differential expression in chemoresistant epithelial ovarian cancer using high-density
Woong Ju1, Byong Chul Yoo, Il-Jin Kim
1Department of Obstetrics and Gynecology and Medical Research Institute, College of Medicine, Ewha Womans University, Seoul, South Korea. goodmorning@ewha.ac.kr
Abstract:
A major obstacle in treatment of epithelial ovarian cancer is chemoresistance. The aim of this study was to determine whether distinct gene expression profiles are associated with chemoresistance in epithelial ovarian carcinoma. We performed global gene expression analysis in 13 primary epithelial ovarian cancer tissues including 5 primary chemosensitive tumors and 8 primary chemoresistant tumors using Affymetrix HGU133A microarray. The gene expression patterns of chemosensitive tumors were compared with those of chemoresistant tumors using fold change. Validity of microarray results was examined by semiquantitative RT-PCR. We identified over 320 genes differentially expressed in chemoresistant epithelial ovarian cancer (> or = twofold). Upregulated genes in chemoresistant tumors included cell cycle regulating genes (TOP2A, BCAT1, CDCA8, CCNA2, CENPE), and genes with previously known mechanisms in tumorigenesis (S100A9, APOA1, RNF125, IFI16). Downregulated genes in chemoresistant tumors included genes related to cell adhesion (MUC5B, CITED2), transcription regulating genes (FOXD1, MAD1L1, PAX2), genes involving signal transduction (SOSTDC1, SNX1, SFRP1, FOXA2, PLK2), and stress protein gene (TP53AP1). These data show that gene expression profiling can discriminate primary chemoresistant from primary chemosensitive ovarian cancers. This type of molecular profiling could provide a basis for additional functional studies.
Insights
Chemoresistance in epithelial ovarian cancer is a major treatment challenge. Gene expression profiling identified over 320 differentially expressed genes, distinguishing chemosensitive from chemoresistant tumors.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Chemoresistance significantly hinders effective treatment of epithelial ovarian cancer.
- Identifying molecular markers for chemoresistance is crucial for personalized therapy.
Purpose of the Study:
- To investigate distinct gene expression profiles associated with chemoresistance in epithelial ovarian cancer.
- To determine if gene expression patterns can differentiate chemosensitive from chemoresistant tumors.
Main Methods:
- Global gene expression analysis using Affymetrix HGU133A microarray on 13 primary epithelial ovarian cancer tissues.
- Comparison of gene expression patterns between chemosensitive (n=5) and chemoresistant (n=8) tumors.
- Validation of microarray findings using semiquantitative RT-PCR.
Main Results:
- Over 320 genes showed differential expression (> or = twofold) in chemoresistant tumors.
- Upregulated genes in chemoresistant tumors included cell cycle regulators (e.g., TOP2A, CCNA2) and tumorigenesis-related genes (e.g., S100A9, APOA1).
- Downregulated genes included those involved in cell adhesion, transcription regulation, signal transduction, and stress response.
Conclusions:
- Gene expression profiling can effectively discriminate between primary chemosensitive and chemoresistant ovarian cancers.
- These findings provide a basis for further functional studies and potential development of molecular diagnostic tools.
