The urinary microparticle tumor-associated calcium-signal transducer 2 as a bladder cancer biomarker

Purpose: In contrast to PSA for prostate cancer, no reliable bladder cancer biomarker is currently widely applicable for the detection and follow-up of bladder cancer. We employed a strategy combining isotopic dimethylation labeling coupled with liquid chromatography-tandem mass spectrometry (LC−MS/MS) to discover bladder cancer biomarkers in urinary microparticles isolated from hernia (control) and bladder cancer patients.

Materials and Methods: The urine specimens of bladder cancer patients and age-matched hernia patients (n = 81) were collected in the morning of surgery. The surgically resected bladder tumors were all pathologically identified and determined into 3 groups for comparison; namely, Low-grade/Early stage (LgEs, n = 40), High-grade/Early stage (HgEs, n = 63), and High-grade/ Advanced-stage (HgAs, n = 37).

Results: A total of 107 proteins out of 2964 proteins were identified in this approach as candidate biomarkers. Differences in the concentrations of 29 proteins were precisely quantified by LC−MRM/MS. There were 24 proteins changed significantly (p  < 0.05) between bladder cancer and hernia. TACSTD2 concentrations measured by LC-MRM/MS were 6.5-fold higher in bladder cancer urinary microparticles than in hernia urinary microparticles. In raw urine specimens (n = 221) using ELISA, the area-under-the-curve values of TACSTD2 was 0.80.

Conclusion: Our study revealed that TACSTD2 showed strong association with bladder canLcer in urine specimens, and thus represents a potential biomarker for noninvasive screening for bladder cancer.