Transcriptional Analysis of Immunohistochemically Defined Subgroups of Non-Muscle-Invasive Papillary High-Grade Upper Tract Urothelial Carcinoma.

Immunohistochemical (IHC) staining for CK5/6 and CK20 was reported to be correlated with the prognosis of early urothelial carcinoma in a way contrary to that of advanced tumors for unknown reasons. We aimed to characterize the gene expression profiles of subgroups of non-muscle-invasive papillary high-grade upper tract urothelial carcinoma (UTUC) classified by CK5/6 and CK20 expression levels: group 1 (CK5/6-high/CK20-low), group 2 (CK5/6-high/CK20-high), and group 3 (CK5/6-low/CK20-high). Expression of group 3 was predictive of worse prognosis of non-muscle-invasive papillary high-grade UTUC. Transcriptional analysis revealed 308 differentially expressed genes across the subgroups. Functional analyses of the genes identified cell adhesion as a common process differentially enriched in group 3 compared to the other groups, which could explain its high-risk phenotype. Late cell cycle/proliferation signatures were also enriched in group 3 and in some of the other groups, which may be used as a prognostic biomarker complementary to CK5/6 and CK20. Group 2, characterized by low levels of genes associated with mitogen-activated protein kinase and tumor necrosis factor signaling pathways, was hypothesized to represent the least cancerous subtype considering its normal urothelium-like IHC pattern. This study would facilitate the application of easily accessible prognostic biomarkers in practice.

International journal of molecular sciences. 2019 Jan 29*** epublish ***

Minsun Jung, Jeong Hoon Lee, Bohyun Kim, Jeong Hwan Park, Kyung Chul Moon

Department of Pathology, Seoul National University College of Medicine, Seoul 03080, Korea. ., Seoul National University Biomedical Informatics (SNUBI), Division of Biomedical Informatics and Systems Biomedical Informatics National Core Research Center, Seoul National University College of Medicine, Seoul 03080, Korea. ., Department of Pathology, Seoul National University College of Medicine, Seoul 03080, Korea. ., Department of Pathology, Seoul National University College of Medicine, Seoul 03080, Korea. ., Department of Pathology, Seoul National University College of Medicine, Seoul 03080, Korea. .

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