Proteomic Tissue-Based Classifier for Early Prediction of Prostate Cancer Progression

Author:

Gao YuqianORCID,Wang Yi-TingORCID,Chen Yongmei,Wang Hui,Young Denise,Shi Tujin,Song Yingjie,Schepmoes Athena A.,Kuo ClaireORCID,Fillmore Thomas L.,Qian Wei-JunORCID,Smith Richard D.ORCID,Srivastava Sudhir,Kagan Jacob,Dobi Albert,Sesterhenn Isabell A.,Rosner Inger L.,Petrovics Gyorgy,Rodland Karin D.,Srivastava Shiv,Cullen Jennifer,Liu TaoORCID

Abstract

Although ~40% of screen-detected prostate cancers (PCa) are indolent, advanced-stage PCa is a lethal disease with 5-year survival rates around 29%. Identification of biomarkers for early detection of aggressive disease is a key challenge. Starting with 52 candidate biomarkers, selected from existing PCa genomics datasets and known PCa driver genes, we used targeted mass spectrometry to quantify proteins that significantly differed in primary tumors from PCa patients treated with radical prostatectomy (RP) across three study outcomes: (i) metastasis ≥1-year post-RP, (ii) biochemical recurrence ≥1-year post-RP, and (iii) no progression after ≥10 years post-RP. Sixteen proteins that differed significantly in an initial set of 105 samples were evaluated in the entire cohort (n = 338). A five-protein classifier which combined FOLH1, KLK3, TGFB1, SPARC, and CAMKK2 with existing clinical and pathological standard of care variables demonstrated significant improvement in predicting distant metastasis, achieving an area under the receiver-operating characteristic curve of 0.92 (0.86, 0.99, p = 0.001) and a negative predictive value of 92% in the training/testing analysis. This classifier has the potential to stratify patients based on risk of aggressive, metastatic PCa that will require early intervention compared to low risk patients who could be managed through active surveillance.

Funder

National Cancer Institute

Publisher

MDPI AG

Subject

Cancer Research,Oncology

Reference51 articles.

1. Cancer statistics, 2020

2. Cancer Facts and Figures 2020https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2020/cancer-facts-and-figures-2020.pdf

3. Spatial genomic heterogeneity within localized, multifocal prostate cancer

4. Substantial interindividual and limited intraindividual genomic diversity among tumors from men with metastatic prostate cancer

5. The Diverse Genomic Landscape of Clinically Low-risk Prostate Cancer

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