Integration of the cancer cell secretome and transcriptome reveals potential noninvasive diagnostic markers for bladder cancer

• Published in: Proteomics. Clinical applications Vol. 18; no. 4; pp. e202300033 - n/a
• Main Authors: Chen, Yi‐Ting, Tu, Wei‐Ju, Ye, Zong‐Han, Wu, Chih‐Ching, Ueng, Shir‐Hwa, Yu, Kai‐Jie, Chen, Chien‐Lun, Peng, Pei‐Hua, Yu, Jau‐Song, Chang, Ying‐Hsu
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01-07-2024
• Subjects: Aged; Biomarkers; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Biomarkers, Tumor - urine; Bladder; Bladder cancer; Cancer; Cell Line, Tumor; Chromatography, Liquid; Design of experiments; DNA microarrays; Female; FLI-1 protein; Gene Expression Regulation, Neoplastic; Hernia; Humans; Liquid chromatography; Male; Mass spectrometry; Mass spectroscopy; Middle Aged; proteome; Secretome; Secretome - metabolism; Tandem Mass Spectrometry; TNPO2; Transcriptome; Transcriptomes; Tumor cell lines; Tumor cells; Tumors; Urinary Bladder Neoplasms - diagnosis; Urinary Bladder Neoplasms - genetics; Urinary Bladder Neoplasms - metabolism; Urinary Bladder Neoplasms - pathology; Urinary Bladder Neoplasms - urine; Urine; Urogenital system; secretome; urine; TNPO2; bladder cancer; proteome
• ISSN: 1862-8346; 1862-8354; 1862-8354
• DOI: 10.1002/prca.202300033

Purpose
Bladder cancer (BLCA) is a major cancer of the genitourinary system. Although cystoscopy is the standard protocol for diagnosing BLCA clinically, this procedure is invasive and expensive. Several urine‐based markers for BLCA have been identified and investigated, but none has shown sufficient sensitivity and specificity. These observations underscore the importance of discovering novel BLCA biomarkers and developing a noninvasive method for detection of BLCA. Exploring the cancer secretome is a good starting point for the development of noninvasive biomarkers for cancer diagnosis.
Experimental Design
In this study, we established a comprehensive secretome dataset of five representative BLCA cell lines, BFTC905, TSGH8301, 5637, MGH‐U1, and MGH‐U4, by liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). Expression of BLCA‐specific secreted proteins at the transcription level was evaluated using the Oncomine cancer microarray database.
Results
The expressions of four candidates—COMT, EWSR1, FUSIP1, and TNPO2—were further validated in clinical human specimens. Immunohistochemical analyses confirmed that transportin‐2 was highly expressed in tumor cells relative to adjacent noncancerous cells in clinical tissue specimens from BLCA patients, and was significantly elevated in BLCA urine compared with that in urine samples from aged‐matched hernia patients (controls).
Conclusions
Collectively, our findings suggest TNPO2 as a potential noninvasive tumor‐stage or grade discriminator for BLCA management.