Abstract
Accumulating research shows that ovarian cancer progression can be influenced by both gene mutations and endometriosis. However, the exact mechanism at hand is poorly understood. In the current study, we explored the expression of KRAS and SIRT1, two genes previously identified as altered in endometriosis and ovarian cancer. Human endometrial samples were obtained from regularly cycling women with endometriosis, ovarian cancer, and endometriosis-associated ovarian cancer between 18 and 50 of age undergoing hysterectomy, and immunohistochemical analyses were performed. The cytoplasmic expression of KRAS was low in eutopic endometrium from women without endometriosis or ovarian cancer; however, it was elevated in those who have been diagnosed with endometriosis, as well as ovarian cancer with or without the presence of endometriosis. Nuclear and cytoplasmic SIRT1 expression was also low within endometrium without either disease. However, nuclear SIRT1 expression was increased in those with endometriosis and ovarian cancer associated with endometriosis. Nuclear but not the cytoplasmic expression of SIRT1 correlated with KRAS expression in ovarian cancers associated with endometriosis. These results suggest roles of KRAS and SIRT1 in endometriosis and endometriosis-associated ovarian cancer. Cytoplasmic KRAS expression proves to be a key biomarker in both diseases, while nuclear SIRT1 may be a new biomarker specific to those with endometriosis and those with both endometriosis and ovarian cancer. Further research of these genes could aid in determining the pathogenesis of both diseases and help in clarifying the development of endometriosis-associated ovarian cancer.
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Acknowledgments
We are very grateful for financial support provided through the South Carolina Ovarian Cancer Foundation.
Funding
This work was supported by the South Carolina Ovarian Cancer Foundation.
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The following authors (BAL, J-WJ, SLY) report potential conflict of interest: Technology related to diagnostic biomarkers for detection of endometriosis is included in a patent pending PCT/US2017/025339.
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Teasley, H.E., Beesley, A., Kim, T.H. et al. Differential Expression of KRAS and SIRT1 in Ovarian Cancers with and Without Endometriosis. Reprod. Sci. 27, 145–151 (2020). https://doi.org/10.1007/s43032-019-00017-4
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DOI: https://doi.org/10.1007/s43032-019-00017-4