ABSTRACT
Stroke remains a leading cause of death and disability worldwide. Despite continuous advances, the identification of key molecular signatures in the hyper-acute phase of ischemic stroke is still a primary interest for translational research on stroke diagnosis, prognosis, and treatment. Data integration from high-throughput -omics techniques has become crucial to unraveling key interactions among different molecular elements in complex biological contexts, such as ischemic stroke. Thus, we used advanced data integration methods for a multi-level joint analysis of transcriptomics and proteomics data sets obtained from mouse brains at 2 h after cerebral ischemia. By modeling net-like correlation structures, we identified an integrated network of genes and proteins that are differentially expressed at a very early stage after stroke. We validated 10 of these deregulated elements in acute stroke, and changes in their expression pattern over time after cerebral ischemia were described. Of these, CLDN20, GADD45G, RGS2, BAG5, and CTNND2 were next evaluated as blood biomarkers of cerebral ischemia in mice and human blood samples, which were obtained from stroke patients and patients presenting stroke-mimicking conditions. Our findings indicate that CTNND2 levels in blood might potentially be useful for distinguishing ischemic strokes from stroke-mimicking conditions in the hyper-acute phase of the disease. Furthermore, circulating GADD45G content within the first 6 h after stroke could also play a key role in predicting poor outcomes in stroke patients. For the first time, we have used an integrative biostatistical approach to elucidate key molecules in the initial stages of stroke pathophysiology and highlight new notable molecules that might be further considered as blood biomarkers of ischemic stroke.
Subject(s)
Biomarkers/blood , Brain/metabolism , Brain/pathology , Ischemic Stroke/blood , Proteomics , Animals , Catenins/blood , Female , Gene Expression Profiling , Gene Expression Regulation , Humans , Intracellular Signaling Peptides and Proteins/blood , Ischemic Stroke/diagnosis , Ischemic Stroke/genetics , Male , Mice, Inbred C57BL , Prognosis , Proteome/metabolism , Transcriptome/genetics , Delta CateninABSTRACT
UNLABELLED: New diagnostic methods for thyroid diseases are still being searched for. Immunohistochemical diagnosis is expanded by the introduction of new biomarkers including ß-catenin (B-Cat). Associations are indicated between the cellular expression of this biomarker and tumor stage, nodal metastases and the degree of tumor cell differentiation. Reports are scarce regarding the plasma level of this biomarker in malignant neoplastic diseases. The aim of the study was to analyze the plasma B-Cat concentration and the possibility of it use in the diagnostics of patients with nodular goiter and papillary thyroid carcinoma. MATERIAL AND METHODS: Plasma B-Cat concentration was determined in 64 patients with goiter and 15 healthy volunteers. The final histopathological examination revealed 41 cases of papillary thyroid carcinoma (PTC) and 13 cases of nodular goiter (NG). RESULTS: A significant increase in B-Cat (p <0.05) in both groups compared to the control group. No differences in the concentrations of biomarker was demonstrated between the PTC and NG groups. After determining the AUC for the tested biomarker, the B-Cat ratio of the area value 0.721 was the strong diagnostic test. CONCLUSIONS: Changes in the plasma B-Cat concentration can be the biomarker of thyroid cancer but it cannot be used for the detection of papillary thyroid carcinoma because of concomitant tumor-like lesions in the thyroid gland.