Yuqiu Ge1,2, Bin Xu3, Hongzhou Cai4, Wentao Jing5, Qiong Ouyang1, Qinbo Yuan6, Xu Li1, Yuanming Fan1, Yang Shen7, Qianqian Shi8, Qiangdong Wang9,10, Li Cui11, Xiaojian Yin12, Gaoxiang Ma13,14. 1. Clinical Metabolomics Center, China Pharmaceutical University, Nanjing, 211198, China. 2. Department of Public Health and Preventive Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, China. 3. Department of Urology, The Affiliated Zhongda Hospital of Southeast University, Nanjing, 210003, China. 4. Department of Urologic Surgery, The Affiliated Cancer Hospital of Nanjing Medical University and Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, Nanjing, 210009, China. 5. Department of Urology, Yixing People's Hospital, Wuxi, 214200, China. 6. Department of Urology, Wuxi Fifth People's Hospital, Wuxi, 214011, China. 7. Department of Urology, The Second Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210000, China. 8. Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, 213000, China. 9. Department of Urology, Huaiyin Hospital of Huai'an City, Huai'an, China. fhhywm@163.com. 10. Department of Urology, Huaiyin People's Hospital of Huai'an City, Huai'an, China. fhhywm@163.com. 11. Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, 213000, China. cuili_changzhou@163.com. 12. State Key Laboratory of Natural Medicines, Clinical Metabolomics Center, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, China. ajian.517@163.com. 13. Clinical Metabolomics Center, China Pharmaceutical University, Nanjing, 211198, China. gaoxiang_ma@163.com. 14. State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, China. gaoxiang_ma@163.com.
Abstract
PURPOSE: Markers are needed to increase the diagnostic accuracy of prostate-specific antigen (PSA) in prostate cancer (PCa) screening. Mounting evidence has shown that plasma proteins can be hopeful biomarkers for cancer diagnosis. METHODS: Tandem mass tag (TMT)-based proteomics and parallel reaction monitoring (PRM) analysis were used to screen the differential proteins and further validated in other independent studies (n = 539). Receiver-operating characteristic (ROC), decision curves and nomograms were applied to assess the diagnostic accuracy of biomarkers. RESULTS: Three candidate proteins (DBP, LCAT and ORM2) were preliminarily screened. Subsequent validation studies revealed significant upregulation of ORM2 in PCa patients across other independent cohorts. ORM2 yielded excellent discriminative power for PCa from benign prostatic hyperplasia (BPH) patients (AUC = 0.861 and 0.814 in validation phases 2a and 2b, respectively). Importantly, the combination of ORM2 and PSA gave better predictive accuracy than PSA alone. We incorporated age, PSA and ORM2 into a nomogram, which yielded C-index of 0.883 in validation phase 2a. A similar C-index of 0.879 was obtained in external validation phase 2b. CONCLUSIONS: In summary, our study suggests that ORM2 could be treated as a complementary biomarker for PSA in distinguishing PCa from BPH.
PURPOSE: Markers are needed to increase the diagnostic accuracy of prostate-specific antigen (PSA) in prostate cancer (PCa) screening. Mounting evidence has shown that plasma proteins can be hopeful biomarkers for cancer diagnosis. METHODS: Tandem mass tag (TMT)-based proteomics and parallel reaction monitoring (PRM) analysis were used to screen the differential proteins and further validated in other independent studies (n = 539). Receiver-operating characteristic (ROC), decision curves and nomograms were applied to assess the diagnostic accuracy of biomarkers. RESULTS: Three candidate proteins (DBP, LCAT and ORM2) were preliminarily screened. Subsequent validation studies revealed significant upregulation of ORM2 in PCa patients across other independent cohorts. ORM2 yielded excellent discriminative power for PCa from benign prostatic hyperplasia (BPH) patients (AUC = 0.861 and 0.814 in validation phases 2a and 2b, respectively). Importantly, the combination of ORM2 and PSA gave better predictive accuracy than PSA alone. We incorporated age, PSA and ORM2 into a nomogram, which yielded C-index of 0.883 in validation phase 2a. A similar C-index of 0.879 was obtained in external validation phase 2b. CONCLUSIONS: In summary, our study suggests that ORM2 could be treated as a complementary biomarker for PSA in distinguishing PCa from BPH.
Authors: Vito Cucchiara; Matthew R Cooperberg; Marc Dall'Era; Daniel W Lin; Francesco Montorsi; Jack A Schalken; Christopher P Evans Journal: Eur Urol Date: 2017-11-10 Impact factor: 20.096
Authors: Rene Cortese; Andrew Kwan; Emilie Lalonde; Olga Bryzgunova; Anna Bondar; Ying Wu; Juozas Gordevicius; Mina Park; Gabriel Oh; Zachary Kaminsky; Justina Tverkuviene; Arvydas Laurinavicius; Feliksas Jankevicius; Dorota H S Sendorek; Syed Haider; Sun-Chong Wang; Sonata Jarmalaite; Pavel Laktionov; Paul C Boutros; Arturas Petronis Journal: Hum Mol Genet Date: 2012-05-22 Impact factor: 6.150
Authors: Dragan Ilic; Mia Djulbegovic; Jae Hung Jung; Eu Chang Hwang; Qi Zhou; Anne Cleves; Thomas Agoritsas; Philipp Dahm Journal: BMJ Date: 2018-09-05