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Identification of overexpression and amplification of ABCF2 in clear cell ovarian adenocarcinomas by cDNA microarray
Hiroshi Tsuda1, Yoichi M Ito, Yasuo Ohashi
1Department of Obstetrics and Gynecology, Laboratory of Gynecologic Oncology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Purpose:
Patients with ovarian clear cell adenocarcinoma generally have a poor response to combination chemotherapy and have overall poorer prognosis than patients with other histologic types of ovarian cancer. Genetic changes in this group of cancer have not been thoroughly explored. Identification of these changes may provide us new therapeutic targets to treat this disease.
Experimental Design:
Genomic and expression array analyses were applied on 30 clear cell ovarian cancer cases and 19 serous cases using a 10,816-element cDNA microarray platform. Further validation and clinical correlation studies were done on differentially expressed genes that are related to chemoresistance.
Results:
Based on array analyses, 12 genes showed a significant increase in DNA and mRNA copy number and 5 genes showed a significant decrease in DNA and RNA copy number in clear cell tumors compared with those in the serous type. One of the genes was ABCF2, which belongs to the ATP-binding cassette gene superfamily and has been shown to amplify in other tumor types. Validation studies were done using real-time quantitative PCR and immunohistochemistry. The results showed significantly higher ABCF2 DNA and mRNA copy number and protein levels in clear cell cases compared with those in serous cases. Furthermore, in 20 clear cell cases with chemo-response data available, ABCF2 cytoplasmic staining was significantly higher in nonresponders than that in the responders (60.0% versus 28.5%; P = 0.0002).
Conclusions:
These data suggest that ABCF2 protein may be a prognostic marker for ovarian clear cell ovarian adenocarcinoma.
Insights
ABCF2 protein may serve as a prognostic marker for ovarian clear cell adenocarcinoma, a cancer type with poor chemotherapy response. Higher ABCF2 levels correlate with chemoresistance and poorer outcomes in patients.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Ovarian clear cell adenocarcinoma exhibits poor response to chemotherapy and a worse prognosis compared to other ovarian cancer types.
- Genetic alterations in this subtype are not well-understood, hindering the development of targeted therapies.
Purpose of the Study:
- To identify genetic changes in ovarian clear cell adenocarcinoma.
- To explore potential therapeutic targets and prognostic markers for this disease.
Main Methods:
- Genomic and expression array analyses were performed on 30 clear cell and 19 serous ovarian cancer cases.
- Validated differentially expressed genes related to chemoresistance using real-time quantitative PCR and immunohistochemistry.
Main Results:
- Array analyses identified 12 genes with increased and 5 with decreased DNA/mRNA copy number in clear cell tumors versus serous type.
- ABCF2 (ATP-binding cassette gene superfamily) showed significantly higher DNA, mRNA, and protein levels in clear cell cases.
- Higher ABCF2 cytoplasmic staining correlated with non-response to chemotherapy in clear cell ovarian cancer patients.
Conclusions:
- ABCF2 protein elevation is significantly associated with clear cell ovarian adenocarcinoma.
- ABCF2 may function as a prognostic marker for ovarian clear cell adenocarcinoma, potentially indicating chemoresistance.
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