1. Expression profile of urothelial transcription factors in bladder biopsies with interstitial cystitis
- Author
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Ken-ichi Inoue, Tomohiko Ichikawa, Kanya Kaga, Tomonori Yamanishi, and Mayuko Kaga
- Subjects
0301 basic medicine ,Pathology ,medicine.medical_specialty ,Biopsy ,Urology ,Urinary Bladder ,Cystitis, Interstitial ,030232 urology & nephrology ,Retinoic acid ,Biology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Cell Line, Tumor ,TP63 ,Gene expression ,medicine ,Humans ,Transcription factor ,Gene ,Principal Component Analysis ,Reverse Transcriptase Polymerase Chain Reaction ,Molecular pathology ,Gene Expression Profiling ,Gene expression profiling ,Reverse transcription polymerase chain reaction ,030104 developmental biology ,chemistry ,Cancer research ,Urothelium ,Biomarkers ,Transcription Factors - Abstract
Objectives To characterize interstitial cystitis pathology based on the expression profile of urothelial tissue-specific master transcription factors. Methods Bladder carcinoma cell lines derived from the urothelial stem cells (epithelial or mesenchymal) were used to identify candidate urothelial master transcription factors. Gene expression was measured with quantitative reverse transcription polymerase chain reaction. From the initial screening of 170 transcription factors (human homologs of Drosophila segmentation genes and known master transcription factors from a database), 28 transcription factors were selected. Subsequently, messenger ribonucleic acid from bladder biopsies of interstitial cystitis patients was purified, and gene expression levels of known urothelial marker genes and candidate master transcription factors were measured. Multivariate expression data were analyzed with spss software. Results Factor analysis decomposed the expression profile into four axes: principal axis 1 included retinoic acid receptors and 17 candidate master transcription factors. Principal axis 2 included KRT5 and five candidates. Principal axis 3 included transcription factor TP63 and two candidates. Principal axis 4 included SHH and two candidates. Principal component analysis segregated biopsies from Hunner's lesion in the principal component 1 (retinoic acid)/principal component 2 (SOX13)/principal component 3 (TP63) space. Conclusions Urothelial master transcription factors could serve as novel diagnostic markers and potentially explain the molecular pathology of interstitial cystitis.
- Published
- 2017