Differential expression at the proteomic level of stem-cell markers and other gene markers in high-grade serous vs. other subtypes of ovarian cancer.

Abstract

Ovarian carcinoma is the most lethal neoplasm and the fifth leading cause of death in women due to gynecological malignancies. It is estimated that there are 225,000 new cases diagnosed and 140,000 deaths occurring annually worldwide. Among the different subtypes, widely heterogeneous high-grade serous ovarian cancer (HGSOC) poses a great challenge to modern chemotherapy due to its high recurrence rate and resistance to standard treatments. Both of those causes are linked to the presence of a small subpopulation of cancer stem cells (CSCs) in the tumor microenvironment. Recent studies suggest that survival timeline and disease recurrence are linked to the variable expression of both cancer CSC and other gene biomarkers in cancer cells. Therefore, using Western blot and immunohistochemistry analyses, we assessed the expression of a host of CSC and other gene products at the whole-cell level in total protein extracts and sub-cellular levels in PFA-fixed cells from three HGSOC and five non-HGSOC cell lines. We found that no CSCmarkers were expressed in monolayer two-dimensional cultures that could differentiate HGSOCs from non-HGSOCs. In fact, no CSC-biomarker proteins were detected in any of the subtypes of the cancer-cell lines in our studies. Upon assessing other gene biomarkers at the proteomic level, we observed prominent differential expression patterns among the HGSOC and non-HGSOC subtypes and even within a subtype but no definite pattern to distinguish HGSOCs from non- HGSOCs. In conclusion, determining a differential protein expression profile in subtypes of ovarian cancer requires much further attention in order to provide earlier detection methods and personalized treatment options for patients.