Dataset Information

Non-Muscle-Invasive Bladder Carcinoma with Respect to Basal Versus Luminal Keratin Expression.

ABSTRACT: Non-muscle-invasive bladder cancer (NMIBC) consists of transcriptional subtypes that are distinguishable from those of muscle-invasive cancer. We aimed to identify genetic signatures of NMIBC related to basal (K5/6) and luminal (K20) keratin expression. Based on immunohistochemical staining, papillary high-grade NMIBC was classified into K5/6-only (K5/6High-K20Low), K20-only (K5/6Low-K20High), double-high (K5/6High-K20High), and double-low (K5/6Low-K20Low) groups (n = 4 per group). Differentially expressed genes identified between each group using RNA sequencing were subjected to functional enrichment analyses. A public dataset was used for validation. Machine learning algorithms were implemented to predict our samples against UROMOL subtypes. Transcriptional investigation demonstrated that the K20-only group was enriched in the cell cycle, proliferation, and progression gene sets, and this result was also observed in the public dataset. The K5/6-only group was closely regulated by basal-type gene sets and showed activated invasive or adhesive functions. The double-high group was enriched in cell cycle arrest, macromolecule biosynthesis, and FGFR3 signaling. The double-low group moderately expressed genes related to cell cycle and macromolecule biosynthesis. All K20-only group tumors were classified as UROMOL "class 2" by the machine learning algorithms. K5/6 and K20 expression levels indicate the transcriptional subtypes of NMIBC. The K5/6Low-K20High expression is a marker of high-risk NMIBC.

SUBMITTER: Jung M

PROVIDER: S-EPMC7589917 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Publications

Non-Muscle-Invasive Bladder Carcinoma with Respect to Basal Versus Luminal Keratin Expression.

Jung Minsun M Jang Insoon I Kim Kwangsoo K Moon Kyung Chul KC

International journal of molecular sciences 20201019 20

Non-muscle-invasive bladder cancer (NMIBC) consists of transcriptional subtypes that are distinguishable from those of muscle-invasive cancer. We aimed to identify genetic signatures of NMIBC related to basal (K5/6) and luminal (K20) keratin expression. Based on immunohistochemical staining, papillary high-grade NMIBC was classified into K5/6-only (K5/6High-K20Low), K20-only (K5/6Low-K20High), double-high (K5/6High-K20High), and d ...[more]

PMID: 33086575

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Project description:There is growing evidence that molecular subtypes (e.g. luminal and basal subtypes) affect the prognosis and treatment response in patients with muscle invasive urinary bladder cancer (invasive urothelial carcinoma, iUC). Modeling these subtypes in pre-clinical animal studies is essential, but it is challenging to produce these subtypes, along with other critical host and tumor features, in experimentally-induced animal models. This study was conducted to determine if luminal and basal molecular subtypes are present in naturally-occurring canine iUC, a cancer that mimics the human condition in other key aspects. RNA sequencing was performed on 29 canine treatment naive iUC tissue samples and on four normal canine bladder mucosal samples. Data were aligned to CanFam 3.1, and differentially expressed genes were identified. Unsupervised hierarchical clustering of these genes revealed two distinct groups (n = 13, n = 16). When genes that distinguish basal and luminal subtypes in human cancer (n = 2015) were used to probe genes differentially expressed between normal canine bladder and iUC, 829 enriched signature genes were identified. Unsupervised hierarchical clustering of these genes revealed two distinct groups comprised of 18 luminal subtype tumors and 11 basal subtype tumors. The enriched genes included MMP9, SERPINE2, CAV1, KRT14, and RASA3 in basal tumors, and PPARG, LY6E, CTSE, CDK3, and TBX2 in luminal tumors. In supervised clustering, additional genes of importance in human iUC were identified in canine iUC associated with claudin-low and infiltrated tumors. A smaller panel of genes (n = 60) was identified that distinguished canine luminal and basal iUC with overall 93.1% accuracy. Immune signature patterns similar to those in human iUC were also identified with the greatest enrichment of immune genes being in the basal subtype tumors. These findings provide additional compelling evidence that naturally-occurring canine iUC is a highly relevant and much needed model of human iUC for translational research.

Dataset Information

Non-Muscle-Invasive Bladder Carcinoma with Respect to Basal Versus Luminal Keratin Expression.

Publications

Non-Muscle-Invasive Bladder Carcinoma with Respect to Basal Versus Luminal Keratin Expression.

Similar Datasets

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