Browsing by Subject "ROC Curve"
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Item Serum exosomal-annexin A2 is associated with African-American triple-negative breast cancer and promotes angiogenesis(BioMed Central Ltd., 2020-01-28) Chaudhary, Pankaj; Gibbs, Lee D.; Maji, Sayantan; Lewis, Cheryl M.; Suzuki, Sumihiro; Vishwanatha, Jamboor K.BACKGROUND: Limited information is available on biomarker(s) for triple-negative breast cancer (TNBC) that can address the higher incidence and aggressiveness of TNBC in African-American (AA) women. Our previous studies have demonstrated annexin A2 (AnxA2) association with exosomes which promotes angiogenesis and metastasis. Therefore, our goal was to examine the expression and function of exosomal-annexin A2 (exo-AnxA2) derived from the serum samples of breast cancer patients. METHODS: The expression of serum exo-AnxA2 and its association with clinicopathological features of the breast cancer patients were determined. The role of serum exo-AnxA2 to promote angiogenesis was determined by an in vivo Matrigel plug assay. RESULTS: Our results show that the expression of serum exo-AnxA2 in breast cancer patients (n = 169; 83.33 +/- 2.040 ng/mL, P < 0.0001) is high compared to non-cancer females (n = 68; 34.21 +/- 2.238 ng/mL). High expression of exo-AnxA2 levels in breast cancer was significantly associated with tumor grade (P < 0.0001), poor overall survival (hazard ratio (HR) 2.802; 95% confidence intervals (CI) = 1.030-7.620; P = 0.0353), and poor disease-free survival (HR 7.934; 95% CI = 1.778-35.398; P = 0.0301). The expression of serum exo-AnxA2 levels was significantly elevated in TNBC (n = 68; 109.1 +/- 2.905 ng/mL; P < 0.0001) in comparison to ER(+) (n = 50; 57.35 +/- 1.545 ng/mL), HER2(+) (n = 59; 78.25 +/- 1.146 ng/mL), and non-cancer females (n = 68; 34.21 +/- 2.238 ng/mL). Exo-AnxA2 showed diagnostic values with a maximum AUC as 1.000 for TNBC, 0.8304 for ER(+), and 0.9958 for HER2(+) compared to non-cancer females. The expression of serum exo-AnxA2 was significantly elevated in AA women with TNBC (n = 29; 118.9 +/- 4.086 ng/mL, P < 0.0001) in comparison to Caucasian-American TNBC (n = 27; 97.60 +/- 3.298 ng/mL) patients. Our in vivo results suggest a role of serum exo-AnxA2 in angiogenesis and its association with aggressiveness of TNBC in AA women. CONCLUSIONS: Our results demonstrated that the expression of serum exo-AnxA2 is high in AA women with TNBC and promotes angiogenesis. These findings suggest that exo-AnxA2 holds promise as a potential prognosticator of TNBC and may lead to an effective therapeutic option.Item Water T2 as an early, global and practical biomarker for metabolic syndrome: an observational cross-sectional study(BioMed Central Ltd., 2017-12-19) Robinson, Michelle D.; Mishra, Ina; Deodhar, Sneha; Patel, Vipulkumar; Gordon, Katrina V.; Vintimilla, Raul; Brown, Kim; Johnson, Leigh A.; O'Bryant, Sid E.; Cistola, David P.BACKGROUND: Metabolic syndrome (MetS) is a highly prevalent condition that identifies individuals at risk for type 2 diabetes mellitus and atherosclerotic cardiovascular disease. Prevention of these diseases relies on early detection and intervention in order to preserve pancreatic beta-cells and arterial wall integrity. Yet, the clinical criteria for MetS are insensitive to the early-stage insulin resistance, inflammation, cholesterol and clotting factor abnormalities that characterize the progression toward type 2 diabetes and atherosclerosis. Here we report the discovery and initial characterization of an atypical new biomarker that detects these early conditions with just one measurement. METHODS: Water T2, measured in a few minutes using benchtop nuclear magnetic resonance relaxometry, is exquisitely sensitive to metabolic shifts in the blood proteome. In an observational cross-sectional study of 72 non-diabetic human subjects, the association of plasma and serum water T2 values with over 130 blood biomarkers was analyzed using bivariate, multivariate and logistic regression. RESULTS: Plasma and serum water T2 exhibited strong bivariate correlations with markers of insulin, lipids, inflammation, coagulation and electrolyte balance. After correcting for confounders, low water T2 values were independently and additively associated with fasting hyperinsulinemia, dyslipidemia and subclinical inflammation. Plasma water T2 exhibited 100% sensitivity and 87% specificity for detecting early insulin resistance in normoglycemic subjects, as defined by the McAuley Index. Sixteen normoglycemic subjects with early metabolic abnormalities (22% of the study population) were identified by low water T2 values. Thirteen of the 16 did not meet the harmonized clinical criteria for metabolic syndrome and would have been missed by conventional screening for diabetes risk. Low water T2 values were associated with increases in the mean concentrations of 6 of the 16 most abundant acute phase proteins and lipoproteins in plasma. CONCLUSIONS: Water T2 detects a constellation of early abnormalities associated with metabolic syndrome, providing a global view of an individual's metabolic health. It circumvents the pitfalls associated with fasting glucose and hemoglobin A1c and the limitations of the current clinical criteria for metabolic syndrome. Water T2 shows promise as an early, global and practical screening tool for the identification of individuals at risk for diabetes and atherosclerosis.