Non-Muscle-Invasive Bladder Carcinoma with Respect to Basal Versus Luminal Keratin Expression
Abstract
1. Introduction
2. Results
2.1. Patient Characteristics
2.2. Differentially Expressed Genes
2.3. Ingenuity Pathway Analysis and Gene Set Enrichment Analysis
2.4. Validation Using the Public Gene-Expression Dataset
3. Discussion
4. Materials and Methods
4.1. Specimen Selection for RNA Sequencing Using Immunohistochemical Staining for K5/6 and K20
4.2. RNA Sequencing
4.3. Differentially Expressed Genes and Functional Analyses
4.4. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
Abbreviations
NMIBC | Non-muscle-invasive bladder cancer |
MIBC | Muscle-invasive bladder cancer |
IHC | Immunohistochemical |
NMIUTUC | Non-muscle-invasive upper tract urothelial carcinoma |
MAPK | Mitogen-activated protein kinase |
DEG | Differentially expressed gene |
GO | Gene ontology |
KEGG | Kyoto Encyclopedia of Genes and Genomes |
IPA | Ingenuity Pathway Analysis |
GSEA | Gene Set Enrichment Analysis |
FDR | False discovery rate |
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Category | Predicted Result | Upregulated Group | z-Score 1 | FDR 2 |
---|---|---|---|---|
K20-only vs. K5/6-only group | ||||
Upstream | RABL6 | K20-only | 2.530 | 5.9 × 10−4 |
Upstream | ID2 | K20-only | 2.208 | 5.5 × 10−3 |
Upstream | EFNA4 | K20-only | 2.449 | 1.9 × 10−2 |
Upstream | PPARGC1A | K20-only | 3.125 | 1.9 × 10−2 |
Upstream | EFNA3 | K20-only | 2.449 | 1.9 × 10−2 |
Upstream | EFNA5 | K20-only | 2.449 | 2.2 × 10−2 |
Upstream | TP53 | K5/6-only | 2.752 | 1.0 × 10−7 |
Upstream | TP63 | K5/6-only | 2.213 | 3.3 × 10−6 |
Upstream | TGFB1 | K5/6-only | 4.169 | 2.3 × 10−5 |
Upstream | PGR | K5/6-only | 2.288 | 8.8 × 10−5 |
Upstream | CDKN2A | K5/6-only | 2.701 | 2.8 × 10−4 |
Upstream | KDM5B | K5/6-only | 3.143 | 3.3 × 10−4 |
Upstream | BRCA1 | K5/6-only | 2.063 | 3.7 × 10−4 |
Upstream | RAF1 | K5/6-only | 3.385 | 3.7 × 10−4 |
Upstream | CDKN1A | K5/6-only | 2.408 | 4.6 × 10−4 |
Upstream | RB1 | K5/6-only | 2.134 | 6.8 × 10−4 |
Upstream | SMARCA4 | K5/6-only | 2.959 | 7.6 × 10−4 |
Upstream | NUPR1 | K5/6-only | 3.413 | 8.5 × 10−4 |
Upstream | IKBKB | K5/6-only | 2.016 | 1.7 × 10−3 |
Upstream | EGF | K5/6-only | 2.089 | 2.0 × 10−3 |
Upstream | HIF1A | K5/6-only | 2.059 | 3.2 × 10−3 |
Upstream | TGF beta | K5/6-only | 2.288 | 3.4 × 10−3 |
Upstream | FSHB | K5/6-only | 2.190 | 6.4 × 10−3 |
Upstream | FGF2 | K5/6-only | 3.083 | 8.0 × 10−3 |
Upstream | JAG1 | K5/6-only | 2.646 | 8.1 × 10−3 |
Upstream | PDGF BB | K5/6-only | 2.652 | 8.9 × 10−3 |
Upstream | IGF1 | K5/6-only | 2.083 | 9.8 × 10−3 |
Upstream | CG | K5/6-only | 2.332 | 1.2 × 10−2 |
Upstream | JUN | K5/6-only | 2.502 | 1.3 × 10−2 |
Upstream | BNIP3L | K5/6-only | 2.630 | 1.9 × 10−2 |
Upstream | CTNNB1 | K5/6-only | 2.630 | 2.3 × 10−2 |
Upstream | Calcineurin A | K5/6-only | 2.200 | 2.9 × 10−2 |
Upstream | EDN1 | K5/6-only | 2.439 | 3.6 × 10−2 |
Upstream | ERK1/2 | K5/6-only | 2.163 | 3.7 × 10−2 |
Upstream | TGFB3 | K5/6-only | 2.926 | 3.8 × 10−2 |
Upstream | STAT3 | K5/6-only | 2.209 | 3.8 × 10−2 |
Disease/function | Endocrine gland tumor | K20-only | 2.213 | 3.1 × 10−8 |
Disease/function | Congenital anomaly of digit | K20-only | 2.000 | 7.3 × 10−3 |
Disease/function | Invasion of tumor cell lines | K5/6-only | 2.069 | 1.3 × 10−5 |
Disease/function | Migration of cells | K5/6-only | 2.102 | 3.4 × 10−5 |
Disease/function | Cell movement | K5/6-only | 2.591 | 4.5 × 10−5 |
Disease/function | Adhesion of tumor cell lines | K5/6-only | 2.481 | 7.4 × 10−4 |
Disease/function | Binding of tumor cell lines | K5/6-only | 2.444 | 8.7 × 10−4 |
Disease/function | Attachment of cells | K5/6-only | 2.040 | 1.5 × 10−3 |
Disease/function | Invasion of breast cancer cell lines | K5/6-only | 2.015 | 1.5 × 10−3 |
Disease/function | Cell movement of breast cancer cell lines | K5/6-only | 2.014 | 4.1 × 10−3 |
Disease/function | Apoptosis of prostate cancer cell lines | K5/6-only | 3.467 | 5.9 × 10−3 |
Disease/function | Formation of gamma H2AX nuclear focus | K5/6-only | 2.345 | 6.1 × 10−3 |
Disease/function | Cell movement of endothelial cells | K5/6-only | 2.190 | 6.3 × 10−3 |
Disease/function | Apoptosis of cancer cells | K5/6-only | 2.420 | 7.0 × 10−3 |
Disease/function | Necrosis of tumor | K5/6-only | 2.495 | 7.7 × 10−3 |
Disease/function | Necrosis of prostate cancer cell lines | K5/6-only | 3.223 | 8.2 × 10−3 |
K20-only vs. double-high group | ||||
Upstream | ERBB2 | K20-only | 3.284 | 7.2 × 10−4 |
Upstream | EP400 | K20-only | 2.449 | 1.8 × 10−3 |
Upstream | E2f | K20-only | 2.199 | 2.8 × 10−3 |
Upstream | RABL6 | K20-only | 3.000 | 5.6 × 10−3 |
Upstream | ID2 | K20-only | 2.563 | 5.6 × 10−3 |
Upstream | ID3 | K20-only | 2.157 | 2.1 × 10−2 |
Upstream | E2F3 | K20-only | 2.534 | 2.1 × 10−2 |
Upstream | MITF | K20-only | 2.575 | 3.0 × 10−2 |
Upstream | SREBF2 | K20-only | 2.557 | 4.7 × 10−2 |
Upstream | TP53 | Double-high | 3.069 | 2.8 × 10−8 |
Upstream | CDKN2A | Double-high | 4.097 | 3.7 × 10−4 |
Upstream | CDKN1A | Double-high | 2.729 | 4.5 × 10−4 |
Upstream | MLXIPL | Double-high | 3.592 | 1.4 × 10−3 |
Upstream | OGA | Double-high | 3.272 | 2.5 × 10−3 |
Upstream | MYCN | Double-high | 2.385 | 8.1 × 10−3 |
Disease/function | DNA replication | K20-only | 2.159 | 8.8 × 10−5 |
Disease/function | Genitourinary adenocarcinoma | K20-only | 2.177 | 1.0 × 10−4 |
Disease/function | Proliferation of connective tissue cells | K20-only | 3.115 | 4.2 × 10−4 |
Disease/function | Growth of connective tissue | K20-only | 2.790 | 5.5 × 10−4 |
Disease/function | Cell proliferation of breast cancer cell lines | K20-only | 2.032 | 2.6 × 10−3 |
Disease/function | Advanced malignant solid tumor | K20-only | 2.228 | 3.6 × 10−3 |
Disease/function | Growth of organism | K20-only | 2.299 | 6.0 × 10−3 |
Disease/function | Advanced lung cancer | K20-only | 2.578 | 6.4 × 10−3 |
Disease/function | Cell cycle progression of tumor cell lines | K20-only | 2.395 | 1.1 × 10−2 |
Disease/function | Visceral metastasis | K20-only | 2.594 | 1.3 × 10−2 |
Disease/function | Metastatic solid tumor | K20-only | 2.228 | 1.3 × 10−2 |
Disease/function | Advanced extracranial solid tumor | K20-only | 2.576 | 1.8 × 10−2 |
Disease/function | Cell death of breast cancer cell lines | Double-high | 2.359 | 2.7 × 10−5 |
Disease/function | Cell death of tumor cell lines | Double-high | 3.092 | 4.4 × 10−5 |
Disease/function | Apoptosis | Double-high | 2.128 | 2.1 × 10−4 |
Disease/function | Gastrointestinal tract cancer | Double-high | 2.000 | 1.1 × 10−3 |
Disease/function | Senescence of cells | Double-high | 2.104 | 1.1 × 10−3 |
Disease/function | Cell death of lung cancer cell lines | Double-high | 2.444 | 3.7× 10−3 |
Disease/function | Colon tumor | Double-high | 2.364 | 7.1 × 10−3 |
Disease/function | Proliferation of hematopoietic progenitor cells | Double-high | 2.005 | 1.6 × 10−2 |
Disease/function | Colorectal tumor | Double-high | 2.078 | 1.6 × 10−2 |
Disease/function | Cytostasis of tumor cell lines | Double-high | 2.145 | 1.8 × 10−2 |
K5/6-only vs. double-high group | ||||
Upstream | EPAS1 | K5/6-only | 2.000 | 3.9 × 10−2 |
Disease/function | NA | NA | NA | NA |
K20-only vs. double-low group | ||||
Upstream | ID3 | K20-only | 2.213 | 1.2 × 10−2 |
Upstream | MYC | K20-only | 2.299 | 1.3 × 10−2 |
Upstream | LLGL2 | K20-only | 2.000 | 4.4 × 10−2 |
Upstream | ERBB3 | K20-only | 2.588 | 4.7 × 10−2 |
Disease/function | Genitourinary tumor | K20-only | 2.017 | 2.1 × 10−3 |
Disease/function | Malignant genitourinary solid tumor | K20-only | 2.139 | 2.1 × 10−3 |
Disease/function | Adenocarcinoma | K20-only | 2.204 | 3.2 × 10−3 |
Disease/function | Anogenital cancer | K20-only | 2.144 | 3.9 × 10−3 |
Disease/function | Incidence of tumor | K20-only | 2.257 | 7.0 × 10−3 |
Disease/function | Carcinoma | K20-only | 2.292 | 7.8 × 10−3 |
Disease/function | Extracranial solid tumor | K20-only | 2.697 | 1.4 × 10−2 |
Disease/function | Malignant solid tumor | K20-only | 2.026 | 2.3 × 10−2 |
Disease/function | Epithelial–mesenchymal transition of breast cell lines | K20-only | 2.108 | 2.8 × 10−2 |
K5/6-only vs. double-low group | ||||
Upstream | TP53 | K5/6-only | 2.086 | 1.8 × 10−4 |
Disease/function | NA | NA | NA | NA |
Category | Predicted Result | Upregulated Group | z-Score 1 | FDR 2 |
---|---|---|---|---|
K20-only_Lund vs. K5/6-only_Lund group | ||||
Upstream | RABL6 | K20-only | 5.014 | 2.4 × 10−27 |
Upstream | ERBB2 | K20-only | 4.092 | 5.9 × 10−24 |
Upstream | FOXM1 | K20-only | 3.818 | 1.7 × 10−16 |
Upstream | MITF | K20-only | 3.962 | 7.6 × 10−15 |
Upstream | FOXO1 | K20-only | 2.493 | 6.7 × 10−12 |
Upstream | LIN9 | K20-only | 3.130 | 3.6 × 10−11 |
Upstream | AREG | K20-only | 3.195 | 1.3 × 10−9 |
Upstream | E2F3 | K20-only | 3.592 | 6.1 × 10−8 |
Upstream | E2f | K20-only | 2.449 | 1.4 × 10−7 |
Upstream | MYBL2 | K20-only | 2.607 | 3.1 × 10−7 |
Upstream | ELAVL1 | K20-only | 3.278 | 2.3 × 10−5 |
Upstream | HSPB1 | K20-only | 2.429 | 3.1 × 10−5 |
Upstream | RARA | K20-only | 4.000 | 5.4 × 10−5 |
Upstream | TAL1 | K20-only | 3.000 | 5.6 × 10−5 |
Upstream | KDM1A | K20-only | 3.434 | 7.1 × 10−5 |
Upstream | ESR1 | K20-only | 3.601 | 1.0 × 10−4 |
Upstream | 26s Proteasome | K20-only | 2.357 | 3.5 × 10−4 |
Upstream | BRD4 | K20-only | 2.603 | 3.9 × 10−4 |
Upstream | TRAF2 | K20-only | 2.224 | 6.7 × 10−4 |
Upstream | NSUN6 | K20-only | 2.449 | 4.3 × 10−3 |
Upstream | S100A6 | K20-only | 2.236 | 6.9 × 10−3 |
Upstream | CREB1 | K20-only | 2.219 | 1.5 × 10−2 |
Upstream | TP53 | K5/6-only | 5.972 | 1.4 × 10−14 |
Upstream | TRPS1 | K5/6-only | 3.742 | 3.4 × 10−14 |
Upstream | NUPR1 | K5/6-only | 2.592 | 6.7 × 10−12 |
Upstream | CDKN1A | K5/6-only | 2.783 | 1.4 × 10−7 |
Upstream | KDM5B | K5/6-only | 3.487 | 1.5 × 10−7 |
Upstream | E2F6 | K5/6-only | 2.236 | 4.3 × 10−4 |
Upstream | ATF3 | K5/6-only | 2.369 | 6.0 × 10−4 |
Upstream | CTLA4 | K5/6-only | 2.236 | 5.1 × 10−3 |
Upstream | CDKN2A | K5/6-only | 2.433 | 3.4 × 10−2 |
Disease/function | M phase | K20-only | 2.142 | 1.2x10−12 |
Disease/function | Alignment of chromosomes | K20-only | 2.324 | 7.2 × 10−12 |
Disease/function | M phase of tumor cell lines | K20-only | 2.613 | 5.2 × 10−10 |
Disease/function | Cytokinesis | K20-only | 2.278 | 2.8 × 10−8 |
Disease/function | M phase of cervical cancer cell lines | K20-only | 2.019 | 8.5 × 10−8 |
Disease/function | Cytokinesis of tumor cell lines | K20-only | 2.249 | 1.0 × 10−7 |
Disease/function | Interphase | K20-only | 2.744 | 2.4 × 10−7 |
Disease/function | Cell survival | K20-only | 2.348 | 6.7 × 10−6 |
Disease/function | Cell viability of tumor cell lines | K20-only | 2.470 | 1.3 × 10−5 |
Disease/function | Cell proliferation of tumor cell lines | K20-only | 2.796 | 5.4 × 10−5 |
Disease/function | Cell viability | K20-only | 2.328 | 9.8 × 1−5 |
Disease/function | G1 phase | K20-only | 2.111 | 1.1 × 10−4 |
Disease/function | Mitotic index | K20-only | 2.214 | 5.8 × 10−4 |
Disease/function | Cell viability of myeloma cell lines | K20-only | 2.601 | 3.7 × 10−3 |
Disease/function | Interphase of tumor cell lines | K20-only | 2.017 | 6.0 × 10−3 |
Disease/function | Interphase of cervical cancer cell lines | K20-only | 2.392 | 1.8 × 10−2 |
Disease/function | Cell viability of lung cancer cell lines | K20-only | 2.100 | 4.7 × 10−2 |
Disease/function | Missegregation of chromosomes | K5/6-only | 2.392 | 1.4 × 10−3 |
K20-only_Lund vs. double-high_Lund group | ||||
Upstream | RABL6 | K20-only | 2.828 | 4.2 × 10−4 |
Upstream | ERBB2 | K20-only | 2.219 | 1.2 × 10−2 |
Upstream | TGFB1 | K20-only | 2.186 | 4.3 × 10−2 |
Disease/function | NA | NA | NA | NA |
K5/6-only_Lund vs. double-high_Lund group | ||||
Upstream | KDM5B | K5/6-only | 2.000 | 8.6 × 10−3 |
Upstream | RABL6 | Double-high | 2.236 | 2.2 × 10−4 |
Disease/function | NA | NA | NA | NA |
K20-only_Lund vs. double-low_Lund group | ||||
Upstream | RABL6 | K20-only | 3.207 | 6.4 × 10−10 |
Upstream | FOXM1 | K20-only | 3.382 | 7.1 × 10−8 |
Upstream | ERBB2 | K20-only | 2.538 | 7.1 × 10−7 |
Upstream | MYBL2 | K20-only | 2.412 | 2.3 × 10−6 |
Upstream | LIN9 | K20-only | 2.438 | 7.0 × 10−6 |
Upstream | AREG | K20-only | 2.132 | 2.9 × 10−5 |
Upstream | HIF1A-AS1 | K20-only | 2.236 | 3.6 × 10−4 |
Upstream | 26s Proteasome | K20-only | 2.607 | 2.9 × 10−3 |
Upstream | E2F3 | K20-only | 2.646 | 7.3 × 10−3 |
Upstream | RARA | K20-only | 3.000 | 2.1 × 10−2 |
Upstream | MITF | K20-only | 2.646 | 2.4 × 10−2 |
Upstream | ESR1 | K20-only | 2.718 | 4.8 × 10−2 |
Upstream | TRPS1 | Double-low | 2.828 | 7.1 × 10−7 |
Upstream | TP53 | Double-low | 3.827 | 3.2 × 10−6 |
Upstream | CDKN1A | Double-low | 2.848 | 2.9 × 10−5 |
Upstream | CTLA4 | Double-low | 2.236 | 1.3x10−3 |
Upstream | KDM5B | Double-low | 2.823 | 5.3 × 10−3 |
Disease/function | Segregation of chromosomes | K20-only | 2.000 | 4.9 × 10−4 |
K5/6-only_Lund vs. double-low_Lund group | ||||
Upstream | NA | NA | NA | NA |
Disease/function | NA | NA | NA | NA |
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Jung, M.; Jang, I.; Kim, K.; Moon, K.C. Non-Muscle-Invasive Bladder Carcinoma with Respect to Basal Versus Luminal Keratin Expression. Int. J. Mol. Sci. 2020, 21, 7726. https://doi.org/10.3390/ijms21207726
Jung M, Jang I, Kim K, Moon KC. Non-Muscle-Invasive Bladder Carcinoma with Respect to Basal Versus Luminal Keratin Expression. International Journal of Molecular Sciences. 2020; 21(20):7726. https://doi.org/10.3390/ijms21207726
Chicago/Turabian StyleJung, Minsun, Insoon Jang, Kwangsoo Kim, and Kyung Chul Moon. 2020. "Non-Muscle-Invasive Bladder Carcinoma with Respect to Basal Versus Luminal Keratin Expression" International Journal of Molecular Sciences 21, no. 20: 7726. https://doi.org/10.3390/ijms21207726
APA StyleJung, M., Jang, I., Kim, K., & Moon, K. C. (2020). Non-Muscle-Invasive Bladder Carcinoma with Respect to Basal Versus Luminal Keratin Expression. International Journal of Molecular Sciences, 21(20), 7726. https://doi.org/10.3390/ijms21207726