SH3BGRL3 Protein as a Potential Prognostic Biomarker for Urothelial Carcinoma: A Novel Binding Partner of Epidermal Growth Factor Receptor

Cheng Yao Chiang, Chin Chen Pan, Hong Yi Chang, Ming Derg Lai, Tzong Shin Tzai, Yuh Shyan Tsai, Pin Ling, Hsiao Sheng Liu, Bi Fang Lee, Hong Ling Cheng, Chung Liang Ho, Shu Hui Chen, Nan Haw Chow

研究成果: Article同行評審

28 引文 斯高帕斯(Scopus)


Purpose: Mass spectrometry based biomarker discovery has clinical benefit. To identify novel biomarkers for urothelial carcinoma, we performed quantitative proteomics on pooled urine pairs from patients with and without urothelial carcinoma. Experimental Design: Shot-gun proteomics using liquid chromatography- tandem mass spectrometry and stable isotope dimethyl labeling identified 219 candidate proteins. The potential implication of SH3 domain binding glutamic acid-rich protein like 3 (SH3BGRL3) was examined by immunoblotting of the urine (n = 13) and urothelial tumors (n = 32). Additional immunohistochemistry was performed on bladder cancer array (n = 1145) and correlated with tumor aggressiveness. Then, biologic functions and signaling pathways of SH3BGRL3 were explored using stable cell lines. Results: The detectable urine SH3BGRL3 in patients with urothelial carcinoma was positively associated with higher histologic grading and muscle invasiveness of urothelial carcinoma. SH3BGRL3 is expressed in 13.9% (159/1145) of bladder cancer cohort and is positively associated with muscle invasion (P = 0.0028).SH3BGRL3expression is associated with increased risk of progression in patients with nonmuscle-invasive bladder cancer (P=0.032).SH3BGRL3 expression is significantly associated with a high level of epidermal growth factor receptor (EGFR) in bladder cancer (P < 0.0001). SH3BGRL3 promotes the epithelial mesenchymal transition, cell migration, and proliferation of urothelial carcinoma in vitro. SH3BGRL3 interacts with phosphor-EGFR at Y1068, Y1086, and Y1173 through Grb2 by its proline-rich motif, and activates the Akt-associated signaling pathway. Conclusions: Evaluation of SH3BGRL3 expression status or urine content mayidentify a subset of patients with bladder cancer who may require more intensive treatment. SH3BGRL3 deserves further investigation as a cotargeting candidate for designing EGFR-based cancer therapies.

頁(從 - 到)5601-5611
期刊Clinical Cancer Research
出版狀態Published - 2015 12月 15

All Science Journal Classification (ASJC) codes

  • 腫瘤科
  • 癌症研究


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