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Use of Molecular Markers of Endometrial Receptivity
Published in Botros Rizk, Yakoub Khalaf, Controversies in Assisted Reproduction, 2020
Alejandro Rincón, David Bolumar, Diana Valbuena, Carlos Simón
Moreover, this work postulated the possibility of studying gene expression in the different endometrium layers. One of the first transcriptomic works thus appeared one year later, which used microarrays to evaluate the differential expression between epithelial and stromal cells. In addition, this group hypothesized that WFDC2 and MMP7 in the luminal epithelia layer and decorin and TIMP1 in the stromal compartment could be used as markers during the natural cycle (LH+7) (41). This work started a race to search for transcriptomic biomarkers.
Serum concentrations of HE4 and Ca125 in uncomplicated pregnancies: a longitudinal study
Published in Journal of Obstetrics and Gynaecology, 2020
Bilge Uslu, Selen Dogan, Sebahat Özdem, Tayup Şimşek
HE4 is a product of Whey Acidic Protein 4-disulfide core domain 2 (WFDC2) gene and coexpressed with the other products of the gene as a secretory leukocyte protease inhibitor (SLPI) and Elafin (Bingle et al. 2002; Galgano et al. 2006). They have a significant role in host defence with anti-inflammatory, antiproteinase (neutrophile elastases), antibacterial and antiviral activities (Bingle et al. 2002). It is hypothesised that HE4 may also function as an antiproteinase in the male reproductive system and host defence (Bingle et al. 2002, 2006). WFDC2 is expressed not only in the epididymis but also in lungs, salivary glands, oral cavity, nasopharynx, respiratory tract and most importantly in the normal glandular epithelium of the female reproductive tract (Galgano et al. 2006). Although HE4 protein is normally expressed in normal ovarian tissues, it is over-expressed in case of ovarian cancer (Schummer et al. 1999).
Prognostic value of serum and tissue HE4 expression in ovarian cancer: a systematic review with meta-analysis of 90 studies
Published in Expert Review of Molecular Diagnostics, 2018
Hanyu Cao, Di You, Zhu Lan, Hui Ye, Minmin Hou, Mingrong Xi
A comprehensive literature search on the prognostic role of HE4 in OC was carried out in databases of PubMed, Embase, Web of Science, and China National Knowledge Infrastructure (CNKI) up to 31 July 2017. The medical subject heading (Mesh) terms and full-text words used for searching were as follows: ‘WFDC2 protein, human’ [Supplementary Concept] or ‘human epididymis 4’ OR ‘HE4 protein’ OR ‘human epididymis secretory protein 4’ OR ‘wap 4-disulfide core domain proteins 2’ OR ‘whey acidic protein four disulfide core protein 2’ and ‘ovarian neoplasms’ [Mesh] or ‘ovarian neoplasm’ or ‘ovarian cancer’ or ‘ovarian tumor’ or ‘ovarian tumor’ or ‘ovarian carcinoma’ or ‘ovarian malignancy’ or ‘ovarian adenocarcinoma’. Two investigators independently conducted the initial search and study selection, including removing duplicate or irrelevant publications, screening the titles and abstracts, and identifying studies for full-text review. We also manually screened the citation lists of the retrieved publications to find further relevant trials.
Advances in endometrial cancer protein biomarkers for use in the clinic
Published in Expert Review of Proteomics, 2018
Elena Martinez-Garcia, Carlos Lopez-Gil, Irene Campoy, Julia Vallve, Eva Coll, Silvia Cabrera, Santiago Ramon Y Cajal, Xavier Matias-Guiu, Jan Van Oostrum, Jaume Reventos, Antonio Gil-Moreno, Eva Colas
The best way to identify good biomarkers is to validate them in independent datasets by independent investigators [32]. Accordingly, 10 proteins have been described as differentially abundant between EC and non-EC control women in 3 or more independent validation studies (Table 2). These proteins are HE4, CA125, SLC2A1 (GLUT1), MMP9, FOLR1, VEGFA, CD44, SAA1, TP53, and BCL2. Among them, HE4 (or WFDC2) and CA125 (or MUC16) are the two most studied biomarkers in EC. As shown in Table 2, their increased levels in EC have been confirmed in both tissue and serum samples and in several independent cohorts of patients. HE4 showed a considerably higher sensitivity than CA125 for detecting EC. The sensitivity and specificity values for these 2 proteins reported in the 7 articles presented in the table ranged from 31.5% to 78.8% sensitivity and 65.5% to 100% specificity for HE4 and 17.8% to 52.6% sensitivity and 33.3% to 95% specificity for CA125. These investigations also evaluated the performance of both proteins together. Although a slight improvement in sensitivity has been reported, the combination of CA125 and HE4 does not significantly improve the performance of HE4 alone. The limited sensitivity achieved by these proteins hampers their application in EC diagnosis. Moreover, HE4 and CA125 are not specific biomarkers of EC. Serum concentrations of these two proteins are elevated in various malignancies and have been approved by the FDA as ovarian cancer biomarkers [33]. The diagnostic power of the highlighted proteins and combinations among them should be evaluated in future studies.