Poster Presentation HUPO 2019 - 18th Human Proteome Organization World Congress

Multisialylated LacdiNAc structures on PSA (PSA G-Index®) as a highly specificity-enhanced secondary biomarker for prostate cancer (#890)

Yoshimi Haga 1 , Motohide Uemura 2 , Kengo Takeuchi 3 , Norio Nonomura 2 , Koji Ueda 1
  1. Cancer Precision Medicine Center, Japanese Foundation For Cancer Research, Tokyo, Japan
  2. Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan
  3. Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan

Prostate cancer (PCa) is one of the most commonly diagnosed cancer in men worldwide. Serum prostate specific antigen (PSA) is a powerful biomarker widely used for diagnosing PCa. However, high false positive rate of PSA screening is a great issue to be resolved.

In this study, we performed comprehensive and quantitative profiling of glycan structures on serum PSA using energy resolved oxonium ion monitoring (Erexim) technology (Anal Chem, (2012) 84, 9655) (Patent US8653448, etc.) to improve the specificity and preclude false positive diagnoses of traditional PSA test.

The Erexim parameters of LCMS-8060 triple quadrupole mass spectrometer (Shimadzu) were optimized for quantify multiple glycan structures on PSA. In total 67 glycan structures on PSA, even from 0.1% content structures, were quantitatively monitored in 25 minutes run without enzymatic glycan release or chemical labeling.

As a result of analysis using sera from 15 prostate cancer or 15 benign prostate hyperplasia (BPH) patients whose PSA levels were in “gray zone” (4.0-10.0 ng/ml), abundance of multisialylated LacdiNAc (GalNAcβ1-4GlcNAc) structures were significantly upregulated in the prostate cancer group compared to the BPH group. A couple of these glycoforms were then extracted and subjected to establish a novel prostate cancer-specific diagnosis model (PSA G-Index®). When the diagnostic power was assessed using an independent validation sample set (15 PCa and 15 BPH patients in the PSA gray zone), an AUC of PSA G-index was 1.00, while that of total PSA or PSA f/T ratio was 0.50 or 0.60, respectively. Moreover, both PSA glycoforms showed significant correlation with Gleason scores (Anal Chem, (2019) 91, 2247).

 The analytical basis of PSA G-Index® was already transferred to LSI Medience Corporation to realize the first mass spectrometric cancer diagnostics. Here we’d like to demonstrate intermediary results of the recently-launched larger-scaled validation study to evaluate clinical benefits of PSA G-Index® test.