Characteristics of α2,3-sialyl N-glycosylated PSA as a biomarker for clinically significant prostate cancer in men with elevated PSA level

Tohru Yoneyama, Hayato Yamamoto, Mihoko Sutoh Yoneyama, Yuki Tobisawa, Shingo Hatakeyama, Takuma Narita, Hirotake Kodama, Masaki Momota, Hiroyuki Ito, Shintaro Narita, Fumiyasu Tsushima, Koji Mitsuzuka, Takahiro Yoneyama, Yasuhiro Hashimoto, Wilhelmina Duivenvoorden, Jehonathan H. Pinthus, Shingo Kakeda, Akihiro Ito, Norihiko Tsuchiya, Tomonori HabuchiChikara Ohyama

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The presence of glycosylated isoforms of prostate-specific antigen (PSA) in prostate cancer (PC) cells is a potential marker of their aggressiveness. We characterized the origin of α2,3-sialylated prostate-specific antigen (S23PSA) by tissue-based sialylation-related gene expression and studied the performance of S23PSA density (S23PSAD) alone and in combination with multiparametric magnetic resonance imaging (MRI) for the detection of clinically significant prostate cancer in men with elevated PSA. Methods: Tissue-based quantification of S23PSA and sialyltransferase and sialidase gene expression was evaluated in 71 radical prostatectomy specimens. The diagnostic performance of S23PSAD was studied in 1099 men retrospectively enrolled in a multicenter systematic biopsy (SBx) cohort. We correlated the S23PSAD with Prostate Imaging Reporting and Data System (PI-RADS) scores in 98 men prospectively enrolled in a single-center MRI-targeted biopsy (MRI–TBx) cohort. The primary outcome was the PC-diagnostic performance of the S23PSAD, the secondary outcome was the avoidable biopsy rate of S23PSAD combined with DRE and total PSA (tPSA), and with or without PI-RADS. Results: S23PSA was significantly higher in Gleason pattern 4 and 5 compared with benign prostate tissue. In the retrospective cohort, the performance of S23PSAD for detecting PC was superior to tPSA or PSA density (PSAD) (AUC: 0.7758 vs. 0.6360 and 0.7509, respectively). In the prospective cohort, S23PSAD was superior to tPSA, PSAD, and PI-RADS (AUC: 0.7725 vs. 0.5901, 0.7439 and 0.7305, respectively), and S23PSAD + PI-RADS + DRE + tPSA was superior to DRE + tPSA+PI-RADS with avoidance rate of MRI–TBx (13% vs. 1%) at 30% risk threshold. Conclusions: The diagnostic performance of S23PSAD was superior to conventional strategies but comparable to mpMRI.

Original languageEnglish
Pages (from-to)1411-1427
Number of pages17
JournalProstate
Volume81
Issue number16
DOIs
Publication statusPublished - 2021 Dec 1
Externally publishedYes

Keywords

  • N-glycan
  • PI-RADS
  • PSA
  • biomarker
  • mpMRI
  • prostate cancer
  • sialylation

ASJC Scopus subject areas

  • Oncology
  • Urology

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