A simplified MyProstateScore2.0 for high-grade prostate cancer.

Abstract

<b>Background:</b> The limited diagnostic accuracy of prostate-specific antigen screening for prostate cancer (PCa) has prompted innovative solutions, such as the state-of-the-art 18-gene urine test for clinically-significant PCa (MyProstateScore2.0 (MPS2)). <b>Objective:</b> We aim to develop a non-invasive biomarker test, the simplified MPS2 (sMPS2), which achieves similar state-of-the-art accuracy as MPS2 for predicting high-grade PCa but requires substantially fewer genes than the 18-gene MPS2 to improve its accessibility for routine clinical care. <b>Methods:</b> We grounded the development of sMPS2 in the Predictability, Computability, and Stability (PCS) framework for veridical data science. Under this framework, we stress-tested the development of sMPS2 across various data preprocessing and modeling choices and developed a stability-driven PCS ranking procedure for selecting the most predictive and robust genes for use in sMPS2. <b>Results:</b> The final sMPS2 model consisted of 7 genes and achieved a 0.784 AUROC (95% confidence interval, 0.742-0.825) for predicting high-grade PCa on a blinded external validation cohort. This is only 2.3% lower than the 18-gene MPS2, which is similar in magnitude to the 1-2% in uncertainty induced by different data preprocessing choices. <b>Conclusions:</b> The 7-gene sMPS2 provides a unique opportunity to expand the reach and adoption of non-invasive PCa screening.

EDRN PI Authors
  • (None specified)
Medline Author List
  • Chinnaiyan AM
  • Feng Z
  • Kenney AM
  • Sanda MG
  • Siddiqui J
  • Srivastava S
  • Tang TM
  • Tosoian JJ
  • Wei JT
  • Xiao L
  • Xie C
  • Yu B
  • Zhang Y
  • Zheng Y
PubMed ID
Appears In
Cancer Biomark, 2025 Jan (issue 1)