Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 5601-5611 |
| Number of pages | 11 |
| Journal | Clinical Cancer Research |
| Volume | 21 |
| Issue number | 24 |
| DOIs | |
| Publication status | Published - 2015 Dec 15 |
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All Science Journal Classification (ASJC) codes
- Oncology
- Cancer Research
Cite this
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SH3BGRL3 Protein as a Potential Prognostic Biomarker for Urothelial Carcinoma : A Novel Binding Partner of Epidermal Growth Factor Receptor. / Chiang, Cheng Yao; Pan, Chin Chen; Chang, Hong Yi; Lai, Ming-Derg; Tzai, Tzong Shin; Tsai, Yuh-Shyan; Ling, Pin; Liu, Hsiao-Sheng; Lee, Bi-Fang; Cheng, Hong-Lin; Ho, Chung-Liang; Chen, Shu-Hui; Chow, Nan-Haw.
In: Clinical Cancer Research, Vol. 21, No. 24, 15.12.2015, p. 5601-5611.Research output: Contribution to journal › Article
TY - JOUR
T1 - SH3BGRL3 Protein as a Potential Prognostic Biomarker for Urothelial Carcinoma
T2 - A Novel Binding Partner of Epidermal Growth Factor Receptor
AU - Chiang, Cheng Yao
AU - Pan, Chin Chen
AU - Chang, Hong Yi
AU - Lai, Ming-Derg
AU - Tzai, Tzong Shin
AU - Tsai, Yuh-Shyan
AU - Ling, Pin
AU - Liu, Hsiao-Sheng
AU - Lee, Bi-Fang
AU - Cheng, Hong-Lin
AU - Ho, Chung-Liang
AU - Chen, Shu-Hui
AU - Chow, Nan-Haw
PY - 2015/12/15
Y1 - 2015/12/15
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84954123426&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-14-3308
DO - 10.1158/1078-0432.CCR-14-3308
M3 - Article
C2 - 26286913
AN - SCOPUS:84954123426
VL - 21
SP - 5601
EP - 5611
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 24
ER -