Expression of Duffy antigen receptor for chemokines (DARC) is down-regulated in colorectal cancer

Abstract

Duffy antigen receptor for chemokines (DARC) is a silent chemokine receptor which selectively binds angiogenic chemokines without inducing conventional signaling responses. DARC has been reported to inhibit the development of multiple cancers through clearance of angiogenic chemokines. However, its role in colorectal cancer (CRC) remains unclear. We investigated the expression of DARC in CRC and explored correlation of DARC expression with clinical pathological features and microvessel density (MVD). The protein expression levels of DARC were detected by immunohistochemistry in 90 CRC and 64 paired unaffected tissues. The mRNA levels of DARC were detected by quantitative real-time PCR in 15 CRC and paired unaffected tissues. MVD in CRC was also assessed by immunohistochemistry of CD34. We found that the mRNA and protein expression levels of DARC were significantly lower in CRC than in the unaffected tissues (p?<?0.05). The DARC protein expression levels were positively correlated with DARC mRNA expression levels in both CRC (p?<?0.001) and unaffected tissues (p?<?0.001). We also found that DARC expression was significantly correlated with tumor differentiation (p?<?0.001), lymph node metastasis (p?<?0.01) and TNM stage (p?<?0.05). Moreover, we observed a strong negative relationship between DARC expression and MVD in CRC (p?<?0.001). We showed that DARC expression is down-regulated in CRC and associated with clinical pathological features and MVD of CRC. DARC might be involved in tumorigenesis, progression, angiogenesis, and metastasis of CRC.     

Silencing NPAS2 promotes cell growth and invasion in DLD-1 cells and correlated with poor prognosis of colorectal cancer

Emerging evidences show that circadian rhythm disorder is an important factor of tumor initiation and development. Neuronal PAS domain protein2 (NPAS2), which is the largest circadian gene, has been proved to be a novel prognostic biomarker in breast cancer and non-Hodgkin’s lymphoma. However, the potential functions of NPAS2 in colorectal cancer are still unknown. In our present study, we detected the mRNA expressions of NPAS2 in 108 CRC patients by RT-PCR, and found that NPAS2 expression was significantly down-regulated in tumor tissues than that in NATs. Clinicopathologic analysis revealed that low expression of NPAS2 was associated with the tumor size, TNM stage and tumor distance metastasis in colorectal cancer (p < 0.05). Furthermore, we effectively down-regulated NPAS2 mRNA expression by transfecting RNA interfere fragments into DLD-1 cells, and our results in vitro demonstrated that silencing NPAS2 expression could promote cell proliferation, cell invasion and increase the wound healing ability (p < 0.05). However, down-regulating NPAS2 expression did not influence the apoptotic rate in DLD-1 cells (p > 0.05). In conclusion, our study suggested that NPAS2, functioned as a potential tumor suppressor gene, could serve as a promising target and potential prognostic indicator for colorectal cancer.     

Prediction value of intercellular adhesion molecule-1 gene polymorphisms for epithelial ovarian cancer risk,clinical features,and prognosis

Intercellular adhesion molecule-1 (ICAM-1, encoded by ICAM-1) is implicated in tumorigenesis and tumor progression. ICAM-1 modulates the susceptibility to several types of cancer and the disease prognosis; however, its role in epithelial ovarian cancer (EOC) is unclear. Here, we evaluate single nucleotide polymorphisms (SNPs) in ICAM-1 as predictors of EOC risk and prognosis. Six ICAM-1 polymorphisms were genotyped in 408 patients with EOC and 520 controls using the MassARRAY system. The ICAM-1 mRNA levels in 89 EOC tissues and 35 normal ovarian tissues were examined using quantitative PCR. The ICAM-1 rs5498 G allele was associated with increased tumor grade (OR = 2.650) and EOC risk (OR = 1.405). This risk was more evident in females who had first-degree relatives (FDRs) with a tumor (OR = 3.475) or who experienced early menarche (OR = 2.774). The ICAM-1 expression in the cancerous tissue was elevated compared with that of normal ovarian tissues (p < 0.0001), and it was associated with an rs5498 genotype (p = 0.0002). ICAM-1 SNPs did not significantly predict the overall EOC survival (p > 0.05). However, the rs5498 G allele correlated with EOC survival time in patients whose FDRs suffered from a tumor (p = 0.001). ICAM-1 rs5498 likely confers a high risk for EOC in G allele carriers accompanied by up-regulation of ICAM-1 expression during carcinogenesis. The combination of ICAM-1 rs5498 and tumor history predicts the EOC prognosis.     

Prognostic implications of ENE and LODDS in relation to lymph node-positive colorectal cancer location

BackgroundExtranodal extension (ENE) and log odds of positive lymph nodes (LODDS) are associated with the aggressiveness of both colon and rectal cancers. The current study evaluated the clinicopathological significance and the prognostic impact of ENE and LODDS in the colon and rectal patients independently.MethodsThe clinical and histological records of 389 colorectal cancer (CRC) patients who underwent curative surgery were reviewed.ResultsFor the ENE system, 244 patients were in the ENE1 group and 145 in the ENE2 system. Compared with the ENE1 system, the patients included in the ENE2 system were prone to nerve invasion (P < 0.001) and vessel invasion (P < 0.001) with higher TNM (P = 0.009), higher T category (P = 0.003), higher N category (P < 0.001), advanced differentiation (P = 0.013), more number of positive lymph nodes (NPLN) (P < 0.001), more lymph node ratio (LNR) (P < 0.001), and a higher value of LODDS (P < 0.001). ENE was more frequent in patients with left and rectal than right cancer. For the LODDS system, 280 patients were in the LODDS1 group, and 109 in the LODDS2 group. Compared to the LODDS1 group, the patients included in the LODDS2 group were more prone to nerve invasion (P = 0.0351) and vessel invasion (P < 0.001) with a higher rate of N2 stage, less NDLN (P < 0.001), more NPLN (P < 0.001), more LNR (P < 0.001), and a higher value of ENE (P < 0.001). Based on the results in the univariable analysis, the N, NPLN, LNR, LODDS, and ENE were separately incorporated into five different Cox regression models combined with the same confounders. The multivariable Cox regression analysis demonstrated that all the five staging systems were independent prognostic factors for overall survival.ConclusionThe current study confirmed that the LODDS stage is an independent influence on the prognosis of both CRC and CC patients. ENE is an independent influencing factor on the prognosis of both CRC and CC patients, and the prognostic impact of extracapsular lymph node was observed in both CRC and CC. The frequency of ENE increases from the proximal (right) to the distal (left) colon as well as the rectum. Therefore, combining ENE and LODDS into the current TNM system to compensate for the inadequacy of pN staging needs further investigation.     

Evidences showing association of interleukin-1B polymorphisms with increased risk of gastric cancer in an Indian population

Helicobacter pylori infection is strongly associated with gastric cancer. In the present study, the relationship between interleukin-1B (IL-1B) polymorphism, H. pylori infection, and prevalence of gastric cancer (GC) in patients of North India was evaluated using genomic DNA directly extracted from biopsy tissues for performing PCR-RFLP. A total of 136 GC cases and 110 healthy controls were included for studying polymorphisms in the genotypes of IL-1B−511, −31, +3954 and IL-1RN both in the presence and absence of H. pylori active infection. Results showed that the frequency of IL-1RN 2/2 was significantly higher in GC cases (21.32%) than the controls (9.09%) with an odds ratio (OR) of 4.391 (95% CI 1.093-10.131). The risk of GC was also found higher in other genotypes of IL-1B namely, −511 TT (χ² = 18.975, p < 0.001), −31CC (χ² = 21.219, p < 0.001), +3954 CT (χ² = 21.082, p < 0.001) and IL-1RN 1/2 (χ² = 30.543, p < 0.001) with active infection of H. pylori. Our findings indicate that the IL-1B and IL-1RN polymorphisms are associated with the development of GC and H. pylori infection markedly increases the risk of GC in North Indian population. Additionally, IL-1B−511 C/C and IL-RN 2/2 polymorphisms seem to be involved in the development of GC in H. pylori uninfected patients.     

Impact of MMP-3 and TIMP-3 gene polymorphisms on prostate cancer susceptibility in North Indian cohort

Purpose

Matrix metalloproteinases (MMPs) have been implicated in progression and metastases of different tumors. The balance between the MMPs and their natural inhibitors (tissue inhibitors of matrix metalloproteinases; TIMP) seem to be an important factor related to its role. The purpose of this study was to evaluate polymorphisms in the MMP-3 and TIMP-3 genes for their associations with prostate cancer (PCa) risk in North Indians.

Materials and methods

Genotypes were determined by PCR-RFLP (Polymerase Chain Reaction Restriction Fragment Length Polymorphism) method in 150 PCa patients and 200 age matched controls of similar ethnicity.

Results

We found significant association in the MMP-3(1171)5A/6A and TIMP-3 (1298) C/T polymorphism with PCa risk. Variant genotype (5A/5A) of MMP-3(1171)5A/6A polymorphism had a high PCa risk (p = 0.037, OR = 3.52, 95%CI = 1.08–11.5). Individuals with TIMP-3 (1298) CT genotype as well as T allele showed reduced risk of PCa (p < 0.001; OR = 0.31; 95%CI = 0.18–0.52, and p = 0.001; OR = 0.49; 95%CI = 0.32–0.75). This effect was even more evident in case of T allele carrier (CT + TT) (p < 0.001; OR = 0.36; 95%CI = 0.22–0.59). Overall no significant association was observed statistically in MMP-3 and TIMP-3 with any of the grading stages and smoking habits in PCa. Haplotype analysis of MMP-3 showed that A-5A-A was associated with three folds (OR = 3.06; 95%CI = 1.71–5.47; p < 0.001) increased risk in PCa patients.

Conclusion

This is the first reported association between polymorphisms in the MMP-3 and TIMP-3 gene and PCa risk and supports the hypothesis that the protease/antiprotease balance has an important role. Due to the small sample size further investigations need to be done to prove a statistical significant correlation between the MMP/TIMP expression and clinicopathological parameters.     

Sex differences in the effect of birth order and parents’ educational status on stunting: A study on Bengalee preschool children from eastern India

One of the greatest problems facing developing countries, including rural India, is undernutrition in terms of stunting among under 5-year-old children. However, there exists scanty information on the prevalence of stunting among preschool children in India and in particular in West Bengal. This study investigated prevalence of stunting and identified the predictor(s) of stunting among 1-5-year-old Bengalee rural preschool children of Integrated Child Development Services (ICDS) centres. This cross-sectional study was undertaken at different ICDS centres of Chapra Block, Nadia District, West Bengal, India. A total of 673 preschool children (323 boys and 350 girls), aged 1-5 years were selected from 30 randomly selected ICDS centres to study the impact of parents’ educational status and child birth order on stunting. The overall (age and sex combined) rate of stunting was 39.2%. Child birth order (BO) (χ² = 14.10, df = 1, p < 0.001), father educational status (FES) (χ² = 21.11, p < 0.001) and mother educational status (MES) (χ² = 14.34, df = 1, p > 0.001) were significantly associated with the prevalence of stunting among girls. Logistic regression analyses revealed that both FES (Wald = 19.97, p < 0.001) as well as MES (Wald = 13.95, p < 0.001) were strong predictors of stunting among girls. Similarly BO (Wald = 13.71, p < 0.001) was a strong predictor of stunting among girls. Girls with ≥3rd BO had significantly higher risk (OR = 2.49, CI = 1.54-4.03) of stunting than those with ≤2nd BO. Moreover, girls with FES lower than secondary level had significantly (OR = 3.30, CI = 1.96-5.58) higher rate of stunting than those with FES ≥ secondary level. Similarly, girls with MES < secondary level had significantly (OR = 2.50, CI = 1.54-4.03) higher rate of stunting than those with FES ≥ secondary level.In conclusion our study revealed that BO as well as parents’ educational status were strong predictors of stunting among girls but not boys. Sex discrimination could be a likely cause for this sex difference in the impact of BO and parents’ educational status.     

Macrophage-conditioned medium inhibits differentiation-induced Rb phosphorylation in 3T3-L1 preadipocytes

This study examines the mechanisms underlying the anti-adipogenic effect of macrophage-secreted products. 3T3-L1 preadipocytes were induced to differentiate over 8 days in medium conditioned by murine J774 macrophages (MacCM). The inhibitory effect on lipid accumulation and expression of adipogenic markers was diminished when addition of MacCM was delayed to day 2 of differentiation. Clonal expansion, an early event required for 3T3-L1 adipogenesis, was reduced in the presence of MacCM (89%; n = 3; p < 0.001), and BrdU incorporation was impaired by 55% (n = 3; p < 0.01). Activation of ERK1/2 was not affected by MacCM, and neither was the expression of p27^kip1, a cyclin-dependent kinase inhibitor. However, phosphorylation of the retinoblastoma protein (Rb), required for cell cycle progression, was impaired by MacCM (94% inhibition; n = 3; p < 0.01). Differentiation-dependent expression, nuclear localization, and DNA binding ability of C/EBPβ were not inhibited by MacCM. Alterations in cell cycle-associated proteins may be important with respect to the anti-adipogenic action of MacCM.     

A panel of differentially methylated regions enable prognosis prediction for colorectal cancer

We aim to identify a panel of differentially methylated regions (DMRs) for predicting survival outcomes for patients with CRC from the TCGA (n = 393). Four DMRs (MUC12, TBX20, CHN2, and B3GNT7) were selected as candidate prognostic markers for CRC. The prediction potential of selected DMRs was validated by the targeted bisulfite sequencing method in an independent cohort with 251 Chinese CRC patients. DMR methylation scores (DMSs) were constructed to evaluate the prognosis of CRC. Results of the validation cohort confirmed that higher DMSs were associated with poor overall survival (OS) of CRC, with hazard ratio (HR) value ranged from 1.445 to 2.698 in multivariable Cox models. Patients in the high prognostic index (high-PI) group showed a markedly unfavorable prognosis compared to the low-PI group in both TCGA discovery cohort (HR = 3.508, 95%CI: 2.196–5.604, P < 0.001) and independent validation cohort (HR = 1.912, 95%CI: 1.258–2.907, P = 0.002).     

Detection of multiple cytokines in the urine of patients with focal necrotising glomerulonephritis may predict short and long term outcome of renal function

Background

Detection of urinary cytokines in pauci-immune focal segmental necrotizing glomerulonephritis (FSNGN) may provide valuable information about disease pathogenesis and prognosis.

Methods

Epidermal growth factor (EGF), transforming growth factor (TGF-β1) and vascular endothelial growth factor (VEGF) were measured by ELISA, and Interleukins, monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein (MIP1β) by a multiplex cytokine assay, in 38 patients with FSNGN. Their levels were correlated with severity of histological findings and renal function outcome in short and long term.

Results

The percentage of crescents in renal biopsy had positive correlation with TGF-β1 (p = 0.004) and IL-15 urinary excretion (p = 0.01), and negative correlation with EGF (p = 0.01). Increased urinary excretion of IL-6, IL-15, VEGF and MIP-1β was associated with poor renal function outcome, but increased levels of EGF, IL-2 and IL-9 predicted a favourable prognosis. In multiple regression analysis IL-6 and VEGF urinary levels were independent predictors of no-response at the acute phase (p = 0.001 and p < 0.0001, respectively), while, IL-6 was the only factor (p = 0.03) predicted worse outcome at the end of follow-up (39.4 ± 45 months).

Conclusion

Increased urinary excretion of IL-6, IL-15, VEGF, TGF-β1, MCP-1 and MIP-1β and reduced EGF, IL-2, IL-9 may be associated with histological damage and influence response to treatment in pauci-immune FSNGN.     

Circulating kisspeptin levels exhibit sexual dimorphism in adults, are increased in obese prepubertal girls and do not suffer modifications in girls with idiopathic central precocious puberty

The system KISS1-KISS1R is one of the main regulators of the hypothalamic-pituitary-gonadal axis and constitutes a link between metabolism and reproduction through its interaction with leptin. The aim of this study was to clarify the possible utility of kisspeptin as a pubertal marker and/or the possible influence of nutritional status in kisspeptin levels. To this end, we have studied kisspeptin plasma levels throughout sexual development and in prepubertal obese girls and girls affected by idiopathic central precocious puberty (CPP). Plasma kisspeptin concentrations were analyzed by RIA. An increase in kisspeptin levels was observed in adult females compared to healthy prepubertal and pubertal girls (p < 0.001) and to adult males (p < 0.001). Additionally, kisspeptin was increased in prepubertal obese girls compared to healthy prepubertal girls (p < 0.01) and girls with idiopathic CPP (p < 0.05). As revealed by the regression analysis, in prepubertal healthy and obese girls and girls with idiopathic CCP, the parameters that influenced kisspeptin levels were BMI (R² = 0.10, p < 0.05) and leptin levels (R² = 0.14, p < 0.01). In conclusion, kisspeptin levels do not seem to be a good pubertal marker. The results obtained in prepubertal and idiopathic CCP girls point to a relationship between leptin, BMI and kisspeptin at least in this group, and suggest a possible role for adipose tissue in the modulation kisspeptin synthesis.     

Higher serum sPD-L1 levels after radiotherapy indicate poor outcome in hepatocellular carcinoma patients

BackgroundOur preclinical research reveals that radiotherapy (RT) promoted PD-L1 upregulation in tumor tissues and that higher PD-L1 after RT worsened the prognosis through immunosuppression. We sought to validate our experimental results in clinical cohorts and promote clinical application.Patients and methodsIn cohort 1, formalin-fixed paraffin-embedded samples were obtained from 46 HCC patients, 23 of whom received preoperative RT and the other 23 received direct surgery. A prospectively collected database contained 122 HCC patients treated with liver RT were enrolled in cohort 2. Blood samples were taken a day before and two weeks after RT. Patients in cohort 2 were further divided into two groups, exploration (73 patients) and validation (49 patients) groups.ResultsIn cohort 1, RT increased the expression of PD-L1 in tumor tissues (p = 0.001), and PD-L1 levels were associated with decreased cytotoxic T-cell infiltration and a trend toward poor prognosis (p = 0.14). Moreover, PD-L1 expression in tumor tissue positively correlated with soluble (s) PD-L1 in serum (R = 0.421, p = 0.046). Then, in cohort 2, we revealed RT increased sPD-L1 in serum (p < 0.001), which was associated with the number of circulating CD8+ T cells (R = -0.24, p = 0.036), indicating poor survival. Furthermore, patients with higher rate of sPD-L1 increase after RT have better treatment response (p < 0.001), PFS (p = 0.032) and OS (p = 0.045).ConclusionHigher post-RT serum sPD-L1, which may potentiate immune suppression effects, indicates a poor prognosis for HCC patients treated with RT.     

The Metastasis Suppressor,N-myc Downregulated Gene 1 (NDRG1), Is a Prognostic Biomarker for Human Colorectal Cancer

Metastasis remains to be one of the most prevalent causes leading to poor long-term survival of colorectal cancer (CRC) patients. The clinical significances of tumor metastatic suppressor, N-myc downregulated gene 1 (NDRG1), have been inconsistently reported in a variety of cancerous diseases. In this study with 240 CRC clinical specimens, we showed that NDRG1 expression was significantly decreased in most of CRC tissues compared to the paired non-tumor counterparts. Statistical analysis revealed a significant inverse correlation of NDRG1 expression with tumor stage, differentiation status and metastasis. Compared with NDRG1-negative group, NDRG1-positve group had better disease-free/overall survival (p = 0.000) over 5 years’ follow-up. Furthermore, NDRG1 was considered to be an independent prognostic factor for overall survival (p = 0.001) and recurrence (p = 0.003). Our study concludes that NDRG1 is a novel favorable predictor for the prognosis in CRC patients.     

High plasma CXCL10 levels are associated with HCV-genotype 1, and higher insulin resistance, fibrosis, and HIV viral load in HIV/HCV coinfected patients

Background

CXCL10 may contribute to the host immune response against the hepatitis C virus (HCV), liver disease progression, and response to HCV antiviral therapy. The aim of our study was to analyze the relationship among virological, immunological, and clinical characteristics with plasma CXCL10 levels in human immunodeficiency virus (HIV)/HCV-coinfected patients.

Methods

We carried out a cross-sectional study on 144 patients. CXCL10 and insulin were measured using an immunoassay kit. The degree of insulin resistance was estimated for each patient using the homeostatic model assessment (HOMA) method. Insulin resistance was defined as a HOMA index higher than or equal to 3.8. Aspartate aminotransferase (AST) to platelet ratio (APRI), FIB-4, Forns index, HGM1, and HGM2 were calculated.

Results

The variables associated with log₁₀ CXCL10 levels by univariate analysis were age (b = 0.013; p = 0.023), prior AIDS-defining condition (b = 0.127; p = 0.045), detectable plasma HIV viral load (b = 0.092; p = 0.006), log₁₀ HOMA (b = 0.216; p = 0.002), HCV-genotype 1 (b = 0.114; p = 0.071), and liver fibrosis assessed by all non-invasive indexes (log₁₀ APRI (b = 0.296; p = 0.001), log₁₀ FIB-4 (b = 0.436; p < 0.001), log₁₀ Forns index (b = 0.591; p < 0.001), log₁₀ HGM1 (b = 0.351; p = 0.021), and log₁₀ HGM2 (b = 0.215; p = 0.018)). However, in multivariate analysis, CXCL10 levels were only associated with HOMA, detectable plasma HIV viral load, HCV-genotype 1 and FIB-4 (R-square = 0.235; p < 0.001).

Conclusion

Plasma CXCL10 levels were influenced by several characteristics of patients related to HIV and HCV infections, insulin resistance, and liver fibrosis, indicating that CXCL10 may play an important role in the pathogenesis of both HCV and HIV infections.     

Alterations of cholesterol precursor levels in Alzheimer's disease

Cerebral and extracerebral cholesterol metabolism are altered in Alzheimer's disease (AD) as indicated by reduced plasma levels of the cholesterol elimination products 24S-hydroxycholesterol, which is of cerebral origin, and of 27-hydroxycholesterol, which is formed extracerebrally. However, it has to be evaluated, if changes of cholesterol metabolism in the whole body or in the CNS are exclusively due to the altered elimination of cholesterol or are also due to altered de novo synthesis in AD. We investigated CSF and plasma levels of cholesterol and of its precursors lanosterol, lathosterol and desmosterol in AD patients and non-demented controls. We found CSF levels of cholesterol (p = 0.011), absolute levels of all investigated cholesterol precursors (each p < 0.001) and ratios of cholesterol precursors/cholesterol (each < 0.01) to be lower in AD patients as compared to controls. In plasma, the absolute levels of lanosterol (p = 0.026) and lathosterol (p < 0.001) and the ratio of lathosterol/cholesterol (p = 0.002) but none of the other investigated parameters were reduced in AD patients (p > 0.1). Furthermore, ratios of desmosterol/lathosterol in CSF (p = 0.023) and plasma (p = 0.009) were higher in AD patients as compared to controls. Our data support the hypothesis that cholesterol metabolism is altered in AD and further suggest that especially cholesterol de novo synthesis within the CNS of AD patients might be reduced. These findings raise doubt on a beneficial effect of cholesterol lowering treatment in manifest AD.     

High expression of Rab3D predicts poor prognosis and associates with tumor progression in colorectal cancer

Rab3D belongs to Rab protein family. Previous reports showed that the expression of Rab3D was dysregulated in various types of cancer. Rab3D belongsRab3D belongs. However, little is known about the role of Rab3D in carcinogenesis and progression of colorectal cancer (CRC). Here, we first evaluated the expression of Rab3D in 32 fresh CRC and matched normal tissues and found Rab3D was dramatically increased in CRC tissues compared to normal tissues (p < 0.001). Furthermore, immunochemistry was used to investigate Rab3D expression in 300CRC tissue specimens. The expression of Rab3D significantly positively correlated with the tumor size (p = 0.041), CEA level (p = 0.007), tumor classification (p = 0.030), lymphatic metastasis (p < 0.001), distant metastasis (p = 0.013) and clinical stage (p = 0.003). We also demonstrated that overall survival is poor in CRC patients with high expression of Rab3D (p < 0.001). Finally, we showed that Rab3D activated Akt/GSK3β/Snail pathway and induced EMT process in colorectal cancer cells. In conclusion, this study establishes increased Rab3D expression is associated with invasiveness of CRC cells, and Rab3D expression status may serve as a reliable prognostic biomarker in CRC patients.     

Increased urinary glucocorticoid metabolites are associated with metabolic syndrome, hypoadiponectinemia, insulin resistance and β cell dysfunction

Metabolic syndrome (MetS) may have increased cortisol (F) production caused by 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) in liver and adipose tissue and/or by HPA axis dysregulation. F is then mainly metabolized by liver reductases into inactive tetrahydrometabolites (THMs). We measured THM levels in patients with or without MetS and evaluate the correlation between THMs and anthropometric and biochemical parameters. We recruited 221 subjects, of whom 130 had MetS by ATP III. We evaluated F, cortisone (E), adipokines, glucose, insulin and lipid profiles as well as urinary (24 h) F, E and THM levels. β Cell function was estimated by the HOMA Calculator. We observed that patients with MetS showed higher levels of THMs, HOMA-IR and leptin and lower levels of adiponectin and HOMA-β but no differences in F and E in plasma or urine. THM was associated with weight (r = +0.44, p < 0.001), waist circumference (r = +0.38, p < 0.01), glycemia (r = +0.37, p < 0.01), and triglycerides (r = +0.18, p = 0.06) and negatively correlated with adiponectin (r = −0.36, p < 0.001), HOMA-β (r = −0.21, p < 0.001) and HDL (r = −0.29, p < 0.01). In a logistic regression model, THM levels were associated with hypertension, hyperglycemia and dyslipidemia. We conclude that MetS is associated with increased urinary THMs but not with F and E levels in plasma or urine. Increased levels of THM, reflecting the daily cortisol production subsequently metabolized, are correlated with hypoadiponectinemia, hypertension, dyslipidemia, insulin resistance and β cell dysfunction. A subtle increased in glucocorticoid production may further account for the phenotypic and biochemical similarities observed in central obesity and Cushing’s syndrome.