Eppley Institute for Cancer Research, University of Nebraska Medical Center, Omaha, NE, 68198-6805, USA.
Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, 68198-6805, USA.
Sci Rep. 2018 Nov 20;8(1):17136. doi: 10.1038/s41598-018-35567-1.
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.
POTE 家族包括三个进化群的 14 个基因。我们测定了正常组织、上皮性卵巢癌和高级别浆液性卵巢癌(EOC,HGSC)以及泛癌中 POTE mRNA 的表达,并确定了 POTE 表达与卵巢癌临床病理的关系。第 1 组和第 2 组 POTEs 在正常组织中表现出睾丸特异性表达,与癌症睾丸抗原(CTA)的分配一致,而第 3 组 POTEs 在几种正常组织中表达,表明它们不是 CTA。泛 POTE 和个别 POTEs 在 EOC 和 HGSC 中与正常对照相比表达显著升高。泛 POTE 与分期、分级和 HGSC 亚型增加相关。一些特定的 POTEs 在复发性 HGSC 中表达增加,而 POTEE 与降低的 HGSC OS 特别相关。与肿瘤一致,EOC 细胞系与 OSE 和 FTE 细胞相比,泛 POTE 显著升高。值得注意的是,第 1 组和第 2 组 POTEs(POTEs A/B/B2/C/D)、第 3 组 POTE-肌动蛋白基因(POTEs E/F/I/J/KP)和其他第 3 组 POTEs(POTEs G/H/M)表现出组内相关表达,并且对肿瘤和细胞系的泛癌分析证实了这种关系。基于它们在正常组织中的受限表达以及在卵巢癌中表达增加和与不良预后相关,POTEs 是这种恶性肿瘤中潜在的癌基因和治疗靶点。