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Over-expression of Paternally Expressed Gene 10 (PEG10) Is Associated With Poor Prognosis in Upper Tract Urothelial
Mai Okazaki1, Yohei Sekino2, Tetsutaro Hayashi3
1Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Background/Aim:
Upper-tract urothelial carcinomas (UTUCs) are highly aggressive malignancies with a poor prognosis, necessitating the development of new therapeutic targets and biomarkers. Paternally expressed gene 10 (PEG10) functions as a transcription factor and plays an important role in the development and progression of cancer. However, no studies have examined the role of PEG10 in UTUC.
Patients And Methods:
We retrospectively analyzed 103 patients with UTUC who underwent radical nephroureterectomy. We evaluated PEG10 expression using immunohistochemistry and performed in silico analyses using the UTUC public database.
Results:
Immunohistochemistry showed the PEG10 over-expression was associated with lower cancer-specific survival (p=0.018). In the UTUC public database, the high PEG10 expression group had a higher T-category (p<0.001), tumor grade (p=0.016), and non-papillary tumors were more frequent in the high PEG10 expression group (p=0.015). The high PEG10 expression group was significantly correlated with lower disease-specific survival (p=0.004) and progression-free survival (p<0.001). Furthermore, the high PEG10 expression group was observed in both TP53 and RB1 mutated types (p=0.002) and related to the neuroendocrine subtype (p<0.001). Gene Set Enrichment Analysis showed that the high PEG10 expression group is connected to epithelial-mesenchymal transition, G2M checkpoint, E2F targets, mitotic spindle, and myogenesis.
Conclusion:
Over-expression of PEG10 is associated with a poor prognosis in UTUC and may be linked to epithelial-mesenchymal transition. Furthermore, the over-expression of PEG10 may be related to the neuroendocrine subtype. PEG10 may be a biomarker of cancer progression in UTUC and represents a potential therapeutic target.
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