Clinical Validation of a Serum Protein Panel (FLNA， FLNB and KRT19) for Diagnosis of Prostate Cancer.

This study reports on the development of a novel serum protein panel of three prostate cancer biomarkers， Filamin A， Filamin B and Keratin-19 (FLNA， FLNB and KRT19) using multivariate models for disease screening and prognosis. ELISA and IPMRM (LC-MS/MS) based assays were developed and analytically validated by quantitative measurements of the biomarkers in serum. Retrospectively collected and clinically annotated serum samples with PSA values and Gleason scores were analyzed from subjects who underwent prostate biopsy， and showed no evidence of cancer with or without indication of prostatic hyperplasia， or had a definitive pathology diagnosis of prostatic adenocarcinoma. Probit linear regression models were used to combine the analytes into score functions to address the following clinical questions: does the biomarker test augment PSA for population screening? Can aggressive disease be differentiated from lower risk disease， and can the panel discriminate between prostate cancer and benign prostate hyperplasia? Modelling of the data showed that the new prostate biomarkers and PSA in combination were better than PSA alone in identifying prostate cancer， improved the prediction of high and low risk disease， and improved prediction of cancer versus benign prostate hyperplasia.