IGFBP-5 overexpression as a poor prognostic factor in patients with urothelial carcinomas of upper urinary tracts and urinary bladder

Peir In Liang, Yu Hui Wang, Ting Feng Wu, Wen Ren Wu, Alex C. Liao, Kun Hung Shen, Chung Hsi Hsing, Yow Ling Shiue, Hsuan Ying Huang, Han Ping Hsu, Li Tzon Chen, Ching Yih Lin, Chein Tai, Jui Yu Wu, Chien Feng Li

研究成果: 雜誌貢獻文章同行評審

36 引文 斯高帕斯(Scopus)

摘要

Background: Urothelial carcinoma (UC) is prevalent worldwide. Dysregulation of cell growth is a critical event of tumorigenesis and has not been assessed systemically in UC. We thus assessed the published transcriptome of urinary bladder urothelial carcinoma (UBUC) and identified insulin-like growth factor-binding protein-5 (IGFBP-5) as the most significantly upregulated gene associated with the regulation of cell growth. Moreover, validated by using public domain data set, IGFBP-5 expression also significantly predicted worse outcome. IGFBP-5 is one of the binding proteins that regulate insulin-like growth factors (IGFs) and its significance has not been comprehensively evaluated in UCs. Methods: Using immunohistochemistry, we evaluated the IGFBP-5 expression status and its associations with clinicopathological features and survival in 340 cases of upper urinary tract urothelial carcinoma (UTUC) and 295 cases of UBUC. Western blot analysis was used to evaluate IGFBP-5 protein expression in human urothelial cell (HUC) lines. Results IGFBP-5 overexpression was significantly associated with advanced pT stage (p<0.001), high histological grade (UTUC, p<0.001; UBUC, p=0.035), lymph node metastasis (UTUC, p=0.006; UBUC, p=0.004), vascular invasion (UTUC, p<0.001; UBUC, p=0.003), perineural invasion (UTUC, p=0.034; UBUC, p=0.021) and frequent mitosis (UTUC, p<0.001; UBUC, p=0.023). IGFBP-5 overexpression also independently predicted poor disease-specific survival and metastasis-free survival in both groups of patients. Western blot analysis showed IGFBP-5 protein as overexpressed in human urothelial cancer cell lines and not in normal urothelial cancer cells. Conclusions IGFBP-5 plays an important role in tumour progression in UC. Its overexpression is associated with advanced tumour stage and conferred poorer clinical outcome.

原文英語
頁(從 - 到)573-582
頁數10
期刊Journal of Clinical Pathology
66
發行號7
DOIs
出版狀態已發佈 - 七月 2013

ASJC Scopus subject areas

  • 病理學與法醫學

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