Evaluation of the 4Kscore in EPIC: Reply
作者：Karl Smith-Byrne, Georgina K. Fensom, Urwah Noor, Eleanor L. Watts, Naomi E. Allen, Pilar Amiano, María‐Dolores Chirlaque, Marta Crous‐Bou, Marcela Guevara, Verena Katzke, Carlotta Sacerdote, María‐José Sánchez, Matthias B. Schulze, Sabina Sieri, Rosario Tumino, Konstantinos K. Tsilidis, Rudolf Kaaks, Marc J. Gunter, Elio Ríboli, Timothy J. Key, Ruth C. Travis · 发表于：Cancer Epidemiology Biomarkers & Prevention · 年份：2026 · DOI：10.1158/1055-9965.epi-25-1860 · 研究领域：Prostate Cancer Diagnosis and Treatment、Reliability and Agreement in Measurement、Advanced Proteomics Techniques and Applications
We write in response to the letter from Prof. Hans Lilja and Dr. Andrew Vickers with regard to our recent publication in Cancer Epidemiology, Biomarkers & Prevention entitled “Evaluation of the 4Kscore Test in Relation to Subsequent Risk of Aggressive Prostate Cancer in the European Prospective Investigation into Cancer and Nutrition” (1).This project began in 2011 following discussions among Profs. Lilja, Travis, and Key to measure prostate-related proteins in EPIC: microseminoprotein β (MSMB), prostate-specific antigen (PSA) and subforms, and human kallikrein 2 (hK2). Although our initial interest was MSMB, Prof. Lilja suggested including PSA, PSA subforms, and hK2.A pilot study in Prof. Lilja’s laboratory assessed the use of citrated plasma for this project. Only after Profs. Lilja, Travis, and Key all agreed that the samples were suitable did Prof. Lilja’s team subsequently complete all assays (2013–2015). The findings on MSMB, which included the use of total PSA measurements, were published in 2019 with Prof. Lilja as cosenior author (2).Once all data were generated, Prof. Lilja suggested that they would also be suitable to evaluate the discriminative performance of an emerging predictive score for prostate cancer, the 4Kscore. As AUC is a rank-order statistic and very few analyte values were below our lower limits of detection, lower values in our plasma samples—akin to a monotonic transformation—were not likely to influence the relative ranking of participants or the v...