Urinary Proteomics for Noninvasive Prenatal Screening of Trisomy 21: New Biomarker Candidates

Trisomy 21 is a common birth defect in humans. Screening for trisomy 21 is one of the most important tasks in routine prenatal care and robust noninvasive diagnostics are needed in clinical practice. Urinary proteomics offers a new research platform for diagnostics innovation in this context. We report here new biomarker candidates using urinary proteomics profiling. Specifically, we used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to analyze the proteomes of urine samples from 19 pregnant women (aged 28-44 years) carrying fetuses with trisomy 21 and 22 healthy pregnant women (aged 27-42 years) carrying fetuses with normal karyotype. We identified more than 50 differentially expressed proteins between the trisomy 21 group and healthy group, and most of these proteins were associated with the embryonic development. Importantly, tissue inhibitor of metalloproteinases 2 (TIMP2) and lysosomal-associated membrane protein 2 (LAMP2) were further selected as potential urinary protein biomarkers. We found that the combination of TIMP2 and LAMP2 could differentiate fetuses with trisomy 21 from healthy controls with a sensitivity of 74%, a specificity of 82%, and an area under the receiver operating characteristic curves (AUC) value of 0.82 (95% confidence interval, 0.69-0.95). We conclude that TIMP2 and LAMP2 offer promise as biomarker candidates and warrant further clinical research in larger study samples. These findings further our understanding of the pathological processes involved in fetal trisomy 21 and are poised to accelerate the development of new noninvasive potential biomarkers for trisomy 21 prenatal screening.