Search for Amniotic Fluid-Specific Markers: Novel Biomarker Candidates for Amniotic Fluid Embolism

Abstract

Objective: Amniotic fluid embolism (AFE) is a catastrophic syndrome. The amniotic fluid (AF)-specific antigens might be assessed in maternal serum when these proteins abruptly enter maternal circulation. The aims of this study were 1) to review a conventional marker for diagnosis of AFE, and 2) to find AF-specific proteins. Study design: This article reviews the English language literature for identification of proteins specifically or exclusively present in AF. The genome-wide gene expression profiling studies and proteomics-based approaches have been reported to identify the AF-specific proteins. Results: Maternal serum sialosyl Tn (STN), zinc-coproporphyrin-1 (ZnCP-1), tryptase and complement activation are clinically used as biomarkers for detecting AFE. However, these tests are quite limited. With advances in proteomics technology, together with the considerable efforts to find novel diagnostic biomarkers, many candidate proteins have been discovered and reported. Among 44 candidate markers identified in the present review, interleukin(IL)-6, squamous cell carcinoma (SCC), insulin-like growth factor-binding protein (IGFBP)-1, CA125 and osteopontin may be unique AFspecific markers. Conclusion: This paper reviews recent advances in proteomics-based technology providing a significant resource for AFE research and a framework for biomarker discovery. Further research is needed to evaluate the potential functional biomarkers for the diagnosis of AFE.

Identification of interleukin-6 (IL-6) and squamous cell carcinoma (SCC) as amniotic fluid-specific markers

“…Gene expression profiling and proteomics analyses were used to analyze biological samples to identify the AFspecific genes and their products. Many candidates have been discovered and reported as shown in reference [16]. In the present study, AF and MS were collected at term, either before (elective caesarean section) or after the onset of labor (emergency caesarean section).…”

“…We have conducted a document retrieval to identify gene products that are spe-cifically present only in AF but not present in the maternal serum (MS) or proteins/polypeptides that are present in AF at concentrations extremely higher than those in the MS. Proteomic technologies have been predominantly used in the research to discover new AFspecific markers [11][12][13][14][15]. We have previously reported many candidate markers [16]. Enriched protein functions were tumor markers, cell proliferation and embryonic development, metabolism, nervous system, cytokines, immune or complement processes, signaling, cell adhesion and motility, hormones, detoxification system, and metal carrier [16].…”

“…We have previously reported many candidate markers [16]. Enriched protein functions were tumor markers, cell proliferation and embryonic development, metabolism, nervous system, cytokines, immune or complement processes, signaling, cell adhesion and motility, hormones, detoxification system, and metal carrier [16].…”

Squamous cell carcinoma antigen as a novel candidate marker for amniotic fluid embolism

“…We could not estimate the sensitivity and specificity of IGFBP‐1 because of the lack of appropriate serum samples. Nevertheless, it should be noted that the ratio of amniotic fluid levels to maternal serum levels is lower for IGFBP‐1 than for SCC antigen (150 vs 400) . However, it is not possible to confirm the superiority of SCC antigen over IGFBP‐1 as little is known about the diagnostic capabilities of these markers in clinical practice.…”

Incidence, diagnosis and pathophysiology of amniotic fluid embolism

“…Th is approach allowed us to identify several peptides as possible candidate biomarkers. In a recent study, the six antigens: interleukin (IL)-6, squamous cell carcinoma (SCC) antigen, insulin-like growth factor-binding protein (IGFBP)-1, osteopontin (OPN), CA125 and STN, were specifi cally overexpressed in amniotic fl uid (Oi et al 2010;Kobayashi et al 2011). Among these candidate markers, the tests based on IL-6 or SCC seem to be more sensitive and specifi c bedside tests compared with the conventional STN and ZnCP-1 tests for the detection of entry of amniotic fl uid into maternal circulation .…”