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Selective gene expression profiling of mTOR-associated tumor suppressor and oncogenes in ovarian cancer
Piotr Laudański1, Oksana Kowalczuk, Dagmara Klasa-Mazurkiewicz
1Department of Perinatology, Medical University of Bialystok, Poland. plauda@umwb.edu.pl
Abstract:
The aim of this study was to selectively profile the activation status of mammalian target of rapamycin (mTOR)-associated oncogenes and tumor suppressor genes (TSGs) in ovarian cancer specimens, healthy ovaries and benign ovarian tumors, including endometrial cysts. We used a novel type of microfluidic gene array to examine the expression of 15 human tumor suppressors and oncogenes in ovarian cancer specimens of 53 patients, benign ovarian cysts of 29 women (endometrial and simple) and 11 healthy ovaries of individuals in whom the material was obtained during total hysterectomies performed because of fibroid changes. The array was custom-designed to include the following genes: NF1, RHEB, mTOR1, AKT-1, PTEN, TSC1, TSC2, KRAS, RPS6KB1, 4EBP1, TP53, EIF4E, STK11, PIK3CA and BECN1. Confirmatory immunohistochemical detection was performed for a group of selected proteins. Particularly significant differences were observed as to the expression of PTEN (p < 0.0001), TP53 (p = 0.0003), PIK3CA (p = 0.0003) and BECN1 (p = 0.0014) which were shown to be downregulated in cancer patients when compared to healthy ovaries and benign ovarian cysts (endometrial and simple). These markers did not show association with grade or stage of the tumor. Immunohistochemistry showed that PTEN, TP53, PIK3CA and BECN1 proteins are expressed in ovarian cancer. Our results indicate that there are significant differences in the expression of some of the mTOR-related tumor suppressors and oncogenes which could be associated with the pathogenesis of ovarian cancer.
Insights
This study investigated mammalian target of rapamycin (mTOR)-related genes in ovarian cancer. Key tumor suppressor genes PTEN, TP53, PIK3CA, and BECN1 were significantly downregulated in cancer patients, suggesting a role in ovarian cancer development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Ovarian cancer pathogenesis involves complex genetic alterations.
- Mammalian target of rapamycin (mTOR) pathway dysregulation is implicated in various cancers.
- Profiling oncogenes and tumor suppressor genes (TSGs) is crucial for understanding cancer development.
Purpose of the Study:
- To selectively profile the activation status of mTOR-associated oncogenes and TSGs in ovarian cancer.
- To compare gene expression in ovarian cancer, benign ovarian tumors, and healthy ovaries.
- To identify potential biomarkers for ovarian cancer.
Main Methods:
- Utilized a novel microfluidic gene array to examine 15 human tumor suppressors and oncogenes.
- Analyzed gene expression in 53 ovarian cancer specimens, 29 benign ovarian cysts, and 11 healthy ovaries.
- Performed confirmatory immunohistochemical detection for selected proteins.
Main Results:
- Significant downregulation of PTEN (p < 0.0001), TP53 (p = 0.0003), PIK3CA (p = 0.0003), and BECN1 (p = 0.0014) in ovarian cancer compared to healthy and benign tissues.
- These downregulated markers did not correlate with tumor grade or stage.
- Immunohistochemistry confirmed the expression of PTEN, TP53, PIK3CA, and BECN1 proteins in ovarian cancer.
Conclusions:
- Identified significant differences in mTOR-related tumor suppressor and oncogene expression in ovarian cancer.
- PTEN, TP53, PIK3CA, and BECN1 downregulation may be associated with ovarian cancer pathogenesis.
- These genes represent potential targets for further research and therapeutic strategies.
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