Placental protein 14 as a potential biomarker for diagnosis of preterm premature rupture of membranes

Abstract

Premature rupture of membranes (PROM) is a common pregnancy complication that frequently results in maternal and perinatal morbidity. The present methods for diagnosing PROM do not satisfy clinical requirements. The present study aimed to examine the proteome profile of amniotic fluid (AF) and maternal plasma, screen unique proteins in AF, and evaluate their diagnostic value for diagnosing PROM. The proteome profiles of AF and maternal plasma were examined via liquid chromatography coupled with tandem mass spectrometry-based proteomic techniques. The protein expression levels of diagnostic candidates in AF, maternal plasma and vaginal fluid were determined by ELISA analysis and Magnetic Luminex® screening assays. The diagnostic value of potential biomarkers was evaluated using receiver operating characteristic curves. A lateral flow assay was developed based on colloidal gold immunochromatography technology. The present study identified 540 unique proteins in AF, 12 of which were chosen for further detection. The present results demonstrated that expression levels of pulmonary surfactant-associated protein B, BPI fold-containing family A member 1, zymogen granule protein 16 homolog B, EGF-containing fibulin-like extracellular matrix protein 1, keratin, type II cytoskeletal 4, keratin, type I cytoskeletal 19, placental protein 14 (PP14), insulin-like growth factor-binding protein 2, mesothelin and serpin family B member 3 were significantly higher in AF compared with in maternal plasma (P<0.01). Furthermore, PP14 was observed to have excellent diagnostic accuracy for preterm PROM (PPROM), with a respective sensitivity and specificity of 100 and 87.5% when the cutoff value was 0.008 µg/ml. The PP14-based lateral flow assay demonstrated a visual detection threshold of 0.008 µg/ml. The results from the present study suggested that PP14 may be a novel potential biomarker for PPROM, and may be developed into a lateral flow assay for bedside application to rapidly diagnose PPROM.

Current and Emerging Strategies for Prediction and Diagnosis of Prelabour Rupture of the Membranes: A Narrative Review

“…Several techniques have been developed for evaluating PROM apart from the clinical examination in the last many decades. These methods include the nitrazine test, the Fern test, the test for determining fFN in cervicovaginal secretions, intra-amniotic dye injection and various rapid immunoassay tests for detecting protein marker present in the vaginal fluid ( 49 ). However, the diagnosis of PROM becomes a challenge in the presence of a slow or intermittent amniotic fluid leak, excessive blood in cervical-vaginal fluid or in the absence of classic presentation such as sudden painless ‘gush of fluid’ leaking out of the vagina ( 49 , 50 ).…”

“…These methods include the nitrazine test, the Fern test, the test for determining fFN in cervicovaginal secretions, intra-amniotic dye injection and various rapid immunoassay tests for detecting protein marker present in the vaginal fluid ( 49 ). However, the diagnosis of PROM becomes a challenge in the presence of a slow or intermittent amniotic fluid leak, excessive blood in cervical-vaginal fluid or in the absence of classic presentation such as sudden painless ‘gush of fluid’ leaking out of the vagina ( 49 , 50 ). The rupture of foetal membranes is not grossly apparent in approximately 20%–25% of pregnant women; therefore, the research for identifying an ideal diagnostic test is imperative ( 51 ).…”

Good clinical practice advice: Prediction of preterm labor and preterm premature rupture of membranes

“…12 of 540 unique proteins were chosen for further detection. Placental protein 14 was observed to have excellent diagnostic accuracy for P‐PROM, with a respective sensitivity and specificity of 100% and 87.5% when the cut off value was 0.008 μg/mL …”

“…52 The maternal serum and vaginal fluid of soluble vascular cell adhe- to have excellent diagnostic accuracy for P-PROM, with a respective sensitivity and specificity of 100% and 87.5% when the cut off value was 0.008 μg/mL. 54 High-mobility group box 1 (HMGB1) is a novel identified inflammatory cytokine, and the HMGB1-receptor for advanced glycation end products (RAGE) signaling pathway has been associated with many pathophysiological processes, including P-PROM. HMGB1 nuclearcytoplasmic translocation in P-PROM placenta may lead to the binding of HMGB1 to RAGE, resulting in provoking NF-κBp65 activity and the consequent release of MMP-9 and MMP-2, all of which contribute to the P-PROM.…”

Association between single nucleotide polymorphism of immunoregulatory genes and preterm premature rupture of membranes in preterm labour

“…But information about the polymorphism of signaling molecules during PPROM in preterm pregnancy is small, scientific work in this direction can provide resources for analysis of polymorphic markers in associative studies, deepen the concept of the immune link of PPROM and PTL pathways, develop new effective methods of prediction these complications of pregnancy [10,12].…”