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Abstract
The POTE family includes 14 genes in three phylogenetic groups. We determined POTE mRNA expression in normal tissues, epithelial ovarian and high-grade serous ovarian cancer (EOC, HGSC), and pan-cancer, and determined the relationship of POTE expression to ovarian cancer clinicopathology. Groups 1 & 2 POTEs showed testis-specific expression in normal tissues, consistent with assignment as cancer-testis antigens (CTAs), while Group 3 POTEs were expressed in several normal tissues, indicating they are not CTAs. Pan-POTE and individual POTEs showed significantly elevated expression in EOC and HGSC compared to normal controls. Pan-POTE correlated with increased stage, grade, and the HGSC subtype. Select individual POTEs showed increased expression in recurrent HGSC, and POTEE specifically associated with reduced HGSC OS. Consistent with tumors, EOC cell lines had significantly elevated Pan-POTE compared to OSE and FTE cells. Notably, Group 1 & 2 POTEs (POTEs A/B/B2/C/D), Group 3 POTE-actin genes (POTEs E/F/I/J/KP), and other Group 3 POTEs (POTEs G/H/M) show within-group correlated expression, and pan-cancer analyses of tumors and cell lines confirmed this relationship. Based on their restricted expression in normal tissues and increased expression and association with poor prognosis in ovarian cancer, POTEs are potential oncogenes and therapeutic targets in this malignancy.
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1 Eppley Institute for Cancer Research, University of Nebraska Medical Center, Omaha, NE, USA; Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA
2 Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA
3 Department of Biostatistics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA
4 Department of Biostatistics, University of Nebraska Medical Center, Omaha, NE, USA
5 Penn Ovarian Cancer Research Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
6 Department of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA; Department of Gynecologic Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA; Center for Immunotherapy, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA
7 Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA; Department of Biochemistry, University of Nebraska Medical Center, Omaha, NE, USA
8 Eppley Institute for Cancer Research, University of Nebraska Medical Center, Omaha, NE, USA; Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA; Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA