Urinary Protein Biomarker Panel for the Detection of Recurrent Bladder Cancer
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
Authors: Rosser, Charles J.; Chang, Myron; Dai, Yunfeng; Ross, Shanti; Mengual, Lourdes; Alcaraz, Antonio; Goodison, Steve
Background: Up to 70% of patients with non-muscle-invasive bladder cancer (NMIBC) experience disease recurrence, making it one of the most prevalent cancers in the United States. The purpose of this study was to test the performance of a multiplex urinary biomarker assay for the monitoring of voided urine for recurrent bladder cancer. Methods: This retrospective, multicenter study included a total of 125 subjects with a history of bladder cancer. Voided urine specimens were collected before procedure from these subjects (53 with confirmed tumor recurrence and 72 with confirmed non-tumor recurrence) for analysis. A prediction rule generated from the performance characteristics of 10 single biomarkers (IL8, MMP9, MMP10, SERPINA1, VEGFA, ANG, CA9, APOE, SERPINE1, and SDC1) was measured using ELISA. The diagnostic performance of the biomarker panel was assessed using receiver operator curves (ROC) and descriptive statistical values (e.g., sensitivity and specificity). Results: The combination of all 10 biomarkers outperformed any single biomarker with a calculated AUROC for the diagnostic panel of 0.904 [95% confidence interval (CI), 0.853-0.956]. The multiplex assay achieved an overall sensitivity of 79% and specificity of 88% for recurrent bladder cancer and significantly outperformed the Urovysion cytogenetic assay (sensitivity 42%, specificity 94%) and voided urinary cytology (sensitivity 33%, specificity 90%). Conclusions: A diagnostic panel of 10 urinary biomarkers that accurately detects primary bladder cancer also performs well for the detection of recurrent bladder cancer. Impact: The identification of a reliable urine-based surveillance and detection assay would be of benefit to both patients and the healthcare system. (C)2014 AACR.
Description of 22 new alpha-1 antitrypsin genetic variants
ORPHANET JOURNAL OF RARE DISEASES
Authors: Renoux, Celine; Odou, Marie-Francoise; Tosato, Guillaume; Teoli, Jordan; Abbou, Norman; Lombard, Christine; Zerimech, Farid; Porchet, Nicole; Cellier, Colette Chapuis; Balduyck, Malika; Joly, Philippe
Alpha-1 antitrypsin deficiency is an autosomal co-dominant disorder caused by mutations of the highly polymorphic SERPINA1 gene. This genetic disorder still remains largely under-recognized and can be associated with lung and/or liver injury. The laboratory testing for this deficiency typically comprises serum alpha-1 antitrypsin quantification, phenotyping according to the isoelectric focusing pattern and genotyping if necessary. To date, more than 100 SERPINA1 variants have been described and new genetic variants are frequently discovered. Over the past 10 years, 22 new genetic variants of the SERPINA1 gene were identified in the daily practice of the University Medical laboratories of Lille and Lyon (France). Among these 22 variants, seven were Null alleles and one with a M1 migration pattern (M1(Cremeaux)) was considered as deficient according to the clinical and biological data and to the American College of Medical Genetics and Genomics (ACMG) criteria. Three other variants were classified as likely pathogenic, three as variants of uncertain significance while the remaining ones were assumed to be neutral. Moreover, we also identified in this study two recently described SERPINA1 deficient variants: Trento (p.Glu99Val) and S-Donosti (p.Ser38Phe). The current data, together with a recent published meta-analysis, represent the most up-to-date list of SERPINA1 variants available so far.