(PD1-3) Novel bladder cancer biomarkers discovery by microdissected comparative tissue proteomics
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  • 2015-11-30,
  • 上傳者: TUA秘書處,
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以顯微切割之比較組織蛋白體發現新穎膀胱癌生物標記
陳建綸 鍾婷 吳志慶 吳桂芳 余兆松 蔡承翰 張玉生 梁瑩 崔克宏 陳怡婷
林口長庚醫院 泌尿科 長庚大學
Novel bladder cancer biomarkers discovery by microdissected comparative tissue proteomics
Chien-Lun Chen, Ting Chung, Chih-Ching Wu, Kwai-Fong Ng,Jau-Song Yu, Cheng-Han Tsai, Yu-Sun Chang, Ying Liang, Ke-Hung Tsui, Yi-Ting Chen
Department of Urology, Chang Gung Memorial Hospital, Linko  Chang Gung University, Taoyuan , Taiwan
 
Purpose:
More than 380,000 new cases of bladder cancer are diagnosed worldwide, accounting for 150,200 deaths each year. No reliable biomarker for bladder cancer is used clinically. We employed a strategy combining laser microdissection, isobaric tags for relative and absolute quantitation labeling, and liquid chromatography-tandem MS (LC-MS/MS) analysis to profile proteomic changes in fresh-frozen bladder tumor specimens.
Materials and Methods:
Cellular proteins from four pairs of surgically resected primary bladder cancer tumor and adjacent nontumorous tissue were extracted for two batches of isobaric tags for relative and absolute quantitation (iTRAQ) experiments. The DAVID (database for annotation, visualization and integrated discovery) is used for analysis of dysregulated proteins. ELISA were employed for validation of candidate tumor markers in tissues and the age-matched urine specimens from bladder cancer patients and hernia patients as control were compared.
Results:
The iTRAQ experiments identified a total of 3220 proteins. Seven differentially expressed proteins were selected as potential bladder cancer biomarkers for further verification. Immunohistochemical analyses showed significantly elevated levels of three proteins- SLC3A2, STMN1, and TAGLN2- in tumor cells compared with noncancerous bladder epithelial cells, and suggested that TAGLN2 could be a useful tumor tissue marker for diagnosis (AUC= 0.999). The DAVID analysis revealed three top-ranking biological processes as involved in extracellular matrix organization, extracellular structure organization, and oxidation-reduction. ELISA revealed significantly increased urinary levels of both STMN1 and TAGLN2 in bladder cancer subgroups compared with control groups. Urinary TAGLN2 in bladder cancer samples showed the largest fold change (7.13-fold), with an AUC value of 0.70 (p < 0.001, n= 205).
Conclusion:
Our study discovered that TAGLN2 showed the most significant over expression in bladder cancer tissues and urine specimens, and thus represents a potential biomarker for noninvasive screening for bladder cancer.
 
 
 
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    2015-11-30 10:35:00
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    TUA秘書處
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    台灣泌尿科醫學會
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