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Int J Mol Sci. 2019 Jan 29;20(3). pii: E570. doi: 10.3390/ijms20030570.

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

Author information

1
Department of Pathology, Seoul National University College of Medicine, Seoul 03080, Korea. jjunglammy@gmail.com.
2
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. sosal@snu.ac.kr.
3
Department of Pathology, Seoul National University College of Medicine, Seoul 03080, Korea. cherish1107@naver.com.
4
Department of Pathology, Seoul National University College of Medicine, Seoul 03080, Korea. hopemd@hanmail.net.
5
Department of Pathology, SMG-SNU Boramae Medical Center, Seoul 03080, Korea. hopemd@hanmail.net.
6
Department of Pathology, Seoul National University College of Medicine, Seoul 03080, Korea. blue7270@snu.ac.kr.
7
Kidney Research Institute, Medical Research Center, Seoul National University College of Medicine, Seoul 03080, Korea. blue7270@snu.ac.kr.

Abstract

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.

KEYWORDS:

RNA, messenger; carcinoma, papillary; carcinoma, transitional cell; gene expression; gene expression profiling; immunohistochemistry; papillary urothelial carcinoma; transcriptome; upper tract urothelial carcinoma

PMID:
30699951
PMCID:
PMC6386996
DOI:
10.3390/ijms20030570
[Indexed for MEDLINE]
Free PMC Article

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