Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
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Maldescent of the epididymo-testicular unit can occur as an isolated event or as a component of various syndromes. When part of a syndrome, crypto-epididymis is usually accompanied by other genital and/or extragenital features. Epididymis development is primarily regulated by androgens, and successful epididymo-testicular unit development and descent requires an intact hypothalamic-pituitary-gonadal axis. The developing gonadotropin-releasing hormone system is essential for epididymo-testicular descent and is highly sensitive to reduced fibroblast growth factor (FGF) signaling. Our understanding of the impact of FGFR1 in the process of epididymo-testicular descent has recently improved. At later stages of embryonic development, the undifferentiated epididymal mesenchyme is a specific domain for FGFR1 expression. The majority of individuals with syndromic crypto-epididymis, as well as individuals with isolated maldescent of the epididymo-testicular unit, exhibit some disturbance of FGF, FGFR1 and/or genes involved in hypothalamic-pituitary-gonadal axis regulation. However, the mechanisms underlying FGF dysregulation may differ between various syndromes.
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PMID:Involvement of Fibroblast Growth Factors and Their Receptors in Epididymo-Testicular Descent and Maldescent. 2702 26

Screening biomarkers in serum samples for different diseases has always been of great interest because it presents an early, reliable, and, most importantly, noninvasive means of diagnosis and prognosis. Reverse phase protein arrays (RPPAs) are a high-throughput platform that can measure single or limited sets of proteins from thousands of patients' samples in parallel. They have been widely used for detection of signaling molecules involved in diseases, especially cancers, and related regulation pathways in cell lysates. However, this approach has been difficult to adapt to serum samples. Previously, we developed a sensitive method called the enhanced protein array to quantitatively measure serum protein levels from large numbers of patient samples. Here, we further refine the technology on several fronts: 1. simplifying the experimental procedure; 2. optimizing multiple parameters to make the assay more robust, including the support matrix, signal reporting method, background control, and antibody validation; and 3. establishing a method for more accurate quantification. Using this technology, we quantitatively measured the expression levels of 10 proteins: alpha-fetoprotein (AFP), beta 2 microglobulin (B2M), Carcinoma Antigen 15-3(CA15-3), Carcinoembryonic antigen (CEA), golgi protein 73 (GP73), Growth differentiation factor 15 (GDF15), Human Epididymis Protein 4 (HE4), Insulin Like Growth Factor Binding Protein 2 (IGFBP2), osteopontin (OPN) and Beta-type platelet-derived growth factor receptor (PDGFRB) from serum samples of 132 hepatocellular carcinoma (HCC) patients and 78 healthy volunteers. We found that 6 protein expression levels are significantly increased in HCC patients. Statistical and bioinformatical analysis has revealed decent accuracy rates of individual proteins, ranging from 0.617 (B2M) to 0.908 (AFP) as diagnostic biomarkers to distinguish HCC from healthy controls. The combination of these 6 proteins as a specific HCC signature yielded a higher accuracy of 0.923 using linear discriminant analysis (LDA), logistic regression (LR), random forest (RF) and support vector machine (SVM) predictive model analyses. Our work reveals promise for using reverse phase protein arrays for biomarker discovery and validation in serum samples.
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PMID:Quantitative screening of serum protein biomarkers by reverse phase protein arrays. 3022 Sep 70