Circulating Omentin-1 as a Biomarker at the Intersection of Postmenopausal Breast Cancer Occurrence and Cardiometabolic Risk: An Observational Cross-Sectional Study.

Aberrant circulating omentin-1, which is an anti-inflammatory and pro-apoptotic adipokine, has been reported in various solid tumors. Therefore, we investigated whether or not circulating omentin-1 could be associated with postmenopausal BC (PBC) and could be used as a potential diagnostic and clinical tool taking into consideration clinicopathologic features, tumor markers, as well as anthropometric, metabolic, and inflammatory parameters. Serum omentin-1, tumor markers (CA15-3 and CEA); metabolic (insulin, glucose, HOMA index, and serum lipids), anthropometric (BMI, waist circumference, and fat mass), and inflammatory (TNF-α, IL-6, hsCRP) parameters; classic adipokines (leptin and adiponectin); the Mediterranean diet (MedDiet) score; and cardiovascular (CVD) risk were determined in 103 postmenopausal women with pathologically confirmed incident invasive BC, 103 controls matched on age, 51 patients with benign breast lesions (BBL), and 50 obese postmenopausal women of similar age. The mean serum omentin-1 was significantly lower in cases than in controls and patients with BBL (p < 0.001). In the patients, omentin-1 was inversely associated with tumor, metabolic and inflammatory biomarkers, cancer stage, and the number of infiltrated lymph nodes (p < 0.05). In all study participants, omentin-1 was negatively correlated with CVD risk and positively correlated with MedDiet score. Lower circulating omentin-1 was independently associated with PBC occurrence above and beyond known risk factors. According to the ROC curve analysis, the overall diagnostic performance of omentin-1 (0.84, 95% CI 0.79-0.89) is similar to CA15-3. Circulating omentin-1 may be a biomarker at the intersection of PBC and cardiometabolic risk in postmenopausal women, and could be modulated by the adoption of a MedDiet. Further mechanistic and large multicentric prospective and longitudinal studies are required to elucidate the ontological role of omentin-1 in BC and CVD risks, as well as its diagnostic and prognostic ability and its therapeutic potential.

Circulating plasminogen activator inhibitor-1 activity: a biomarker for resectable non-small cell lung cancer?

PURPOSE: Plasminogen activator inhibitor-1 (PAI-1) participates in thrombotic, fibrinolytic, inflammatory and metabolic cascades. Since previous studies have focused on tissue and blood level concentrations, our goal was to investigate for the first time the independent relationship between plasma PAI-1 activity in resectable non small cell lung cancer (NSCLC) taking into consideration its several interfaces and study its diagnostic and prognostic potential. METHODS: In an adequately powered case-control study, plasma PAI-1 activity, metabolic parameters, classic adipokines, hemostatic, inflammatory and tumor biomarkers were measured in 110 consecutive patients with resectable NSCLC and 110 healthy subjects matched on age, sex and date of blood draw. RESULTS: NSCLC patients exhibited significantly higher PAI-1 activity compared to controls (p<0.001). In NSCLC cases, PAI-1 activity correlated with somatometric variables, insulin, WBC, antithrombin III, protein C, plasminogen, IL-6 and tumor size (p<0.05). Plasma PAI-1 activity was independently associated with NSCLC beyond risk factors associated with NSCLC (OR:6.9, 95%CI:2.9-16.6, p<0.001). Plasminogen activity and body mass index emerged as independent predictors of PAI-1 activity in cases. Due to its high specificity, PAI-1 activity could represent a potentially useful parameter in ruling out NSCLC, alone or in combination with serum tumor markers associated with NSCLC. CONCLUSIONS: PAI-1 activity, reflecting PAI-1 functionality, may represent a potentially useful biomarker in NSCLC associated with thrombotic, tumor-promoting and metabolic networks. More clinical studies are needed to explore whether PAI-1 activity may be a practical biomarker in the risk assessment of NSCLC, at the crossroads of hemostasis and metabolism.

Chemerin as a biomarker at the intersection of inflammation, chemotaxis, coagulation, fibrinolysis and metabolism in resectable non-small cell lung cancer.

OBJECTIVES: Chemerin is an emerging adipocytokine at the intersection of inflammation, chemotaxis, thrombosis, fibrinolysis and metabolism. Our aims were 1) to explore circulating chemerin in resectable non-small cell lung cancer (NSCLC) taking into account its several interfaces; 2) to study its diagnostic potential; and 3) to assess its associations with clinicopathological features of NSCLC. MATERIALS AND METHODS: In a large case-control study, serum chemerin, insulin resistance and lipid parameters, classic adipocytokines, inflammatory, coagulation, fibrinolysis and tumor biomarkers were determined in 110 consecutive patients with resectable NSCLC and 110 healthy controls matched on age (± 5 years), gender and date of blood draw (± 1 month). RESULTS: NSCLC cases exhibited significantly elevated circulating chemerin compared to controls (p < 0.001). In NSCLC cases, chemerin was positively associated with Homeostasis model assessment score of insulin resistance (HOMA-IR), fibrinogen, plasminogen activity, tumor and inflammatory biomarkers, adiponectin, number of infiltrated lymph nodes and NSCLC stage. In control participants, circulating chemerin was positively correlated with somatometric, metabolic, lipid, hemostatic and inflammatory biomarkers, and leptin. Serum chemerin was independently associated with NSCLC, above and beyond NSCLC risk factors (OR: 2.20, 95% CI: 1.09-4.40, p = 0.03). In cases, hemostatic parameters (platelet count and plasminogen activity), HOMA-IR, CYFRA 21-1, creatinine and plant food consumption emerged as independent predictors of circulating chemerin (p < 0.05). Serum chemerin greater than 220 µg/L (cut-off point) yielded a sensitivity and a specificity of 63% and 91.8% respectively with a modest discriminative ability (AUC = 0.72, 95% C.I. 0.64-0.79) for the diagnosis of NSCLC. CONCLUSION: Chemerin may represent a potentially useful biomarker in NSCLC integrating tumor-promoting networks, inflammatory and hemostatic mechanisms, and cancer-related metabolic pathways. More preclinical, prospective and longitudinal studies highlighting the pathogenetic role of chemerin in NSCLC are needed to corroborate and extend these data.

Fetuin-A levels and free leptin index are reduced in patients with chronic lymphocytic leukemia: a hospital-based case-control study.

There are limited data on fetuin-A, soluble leptin receptor (sOB-R) and free leptin index (FLI) in patients with chronic lymphocytic leukemia (CLL). The aim of this study was to compare circulating fetuin-A, sOB-R levels and FLI between 95 patients with CLL and 95 matched controls, as well as among different stages of CLL. Circulating fetuin-A was significantly lower in cases than controls (241.9 ± 99.2 vs. 288.8 ± 127.7 µg/mL; p = 0.005). Although circulating sOB-R levels were similar between groups, FLI was lower in cases than controls (0.45 ± 0.42 vs. 0.67 ± 0.57; p = 0.003). Furthermore, lower fetuin-A or FLI, but not sOB-R, were independently associated with CLL (p < 0.05), particularly among overweight/obese individuals. Fetuin-A, s-OB-R and FLI were similar between different stages of CLL severity, or between symptomatic and asymptomatic disease. In conclusion, circulating fetuin-A and FLI, but not sOB-R, were lower in patients with CLL than controls, a finding warranting further investigation.

Circulating fetuin-A in patients with pancreatic cancer: a hospital-based case-control study.

CONTEXT: A proteomic analysis has proposed fetuin-A (alpha-2-HS-glycoprotein) as a new potential marker for pancreatic cancer (PC). OBJECTIVE: Circulating fetuin-A levels in patients with PC. METHODS: Serum fetuin-A was measured in 81 cases with PC and 81 matched controls before the initiation of any treatment. RESULTS: Serum fetuin-A was not independently associated with the presence of PC. Although there was a trend with higher fetuin-A levels across PC stages, comparisons of fetuin-A in patients within different PC prognostic stages revealed no differences. CONCLUSIONS: Circulating fetuin-A was similar between patients and controls and was not associated with the disease severity.

Higher fetuin-A, lower adiponectin and free leptin levels mediate effects of excess body weight on insulin resistance and risk for myelodysplastic syndrome.

OBJECTIVE: Excess body weight has been implicated in the pathogenesis of myelodysplastic syndrome (MDS). We thus explored the role of serum fetuin-A reflecting ectopic hepatic fat deposition when storage capacity of adipocytes has been exceeded, free leptin reflecting overall fat mass and adiponectin reflecting visceral fat mass, all potential mediators of the effects of obesity on insulin resistance and, consequently, to MDS risk. MATERIALS & METHODS: In a hospital-based case-control study, we studied 101 cases with incident, histologically confirmed primary MDS and 101 controls matched on gender, age and date of diagnosis, between 2004 and 2007. Serum fetuin-A, adiponectin, leptin, leptin receptor, free leptin and insulin were determined. RESULTS: Higher serum fetuin-A, lower adiponectin and lower free leptin were all individually and independently associated with higher risk of MDS before and after controlling for matching and risk factors, such as age, gender, date of diagnosis, body mass index (BMI), family history of lymphohematopoietic cancer, smoking history and serum insulin. Interestingly, we have shown that these associations were prominent among overweight/obese individuals and persisted after controlling for BMI and serum insulin indicating that their effects are above and beyond insulinemia only. CONCLUSION: Elevated serum fetuin-A but lower adiponectin and free leptin are associated with higher risk of MDS particularly among overweight/obese individuals. These findings suggest that the association between excessive weight gain and the risk of MDS could be mediated by fetuin-A, adiponectin and free leptin, which may have potential clinical and preventive implications.

Hyperresistinemia is associated with postmenopausal breast cancer.

OBJECTIVE: The constellation of obesity, insulin resistance, and serum adipocytokine levels is associated with the risk and prognosis of postmenopausal breast cancer (PBC). Altered secretion of resistin may underlie the association between overweight/obesity and PBC. We thus explored the association of serum resistin with PBC, taking into account established risk factors, including adipokines and anthropometric, metabolic, and inflammatory markers. METHODS: In a case-control study, we studied 102 postmenopausal women with pathologically confirmed, incident invasive breast cancer and 102 control participants matched on age and time of diagnosis between 2003 and 2010 at the Veterans' Administration General Hospital of Athens (NIMTS Hospital). Serum resistin, adiponectin, leptin, metabolic (homeostasis model assessment score of insulin resistance) and inflammatory (tumor necrosis factor-α, interleukin-6, and high-sensitivity C-reactive protein) parameters, and tumor markers (carcinoembryonic antigen and CA 15-3) were determined. RESULTS: The mean serum resistin level was significantly higher in case participants than in control participants (P < 0.001) in both univariate and multivariable analyses, adjusting for age, date of diagnosis, education, family history of cancer, use of exogenous hormones, alcohol consumption, smoking status, physical activity, reproductive markers, metabolic markers, anthropometric (body mass index and weight circumference) markers, inflammatory markers, and adipokines (odds ratio, 1.17; 95% CI, 1.03-1.34; P = 0.02). In case participants, resistin level correlated significantly with tumor markers and inflammatory parameters, but not with metabolic and anthropometric variables. CONCLUSIONS: Further prospective, longitudinal, and mechanistic studies are needed to determine whether hyperresistinemia is involved in the development of PBC or reflects changes during PBC progression and therefore could be used as a biomarker for PBC. Targeting resistin inhibition could be an effective therapeutic strategy in breast cancer by down-regulating the inflammatory microenvironment in breast tissue.

Serum resistin: a biomarker of breast cancer in postmenopausal women? Association with clinicopathological characteristics, tumor markers, inflammatory and metabolic parameters.

OBJECTIVE: Previous few studies have shown that resistin is significantly elevated in breast cancer (BC) patients. Therefore, we investigated whether serum resistin could be used as a potential diagnostic and prognostic tool for postmenopausal BC (PBC), taking into account clinicopathological features, serum tumor markers, anthropometric, metabolic, and, for the first time, inflammatory parameters. METHODS: Serum resistin, tumor markers (CA 15-3 and CEA), metabolic, anthropometric and inflammatory parameters (TNF-α, IL-6, hsCRP) were determined in 103 postmenopausal women with incident, pathologically confirmed, invasive BC, 103 controls matched on age and time of diagnosis, and 51 patients with benign breast lesions (BBL). RESULTS: Mean serum resistin was significantly higher in cases than in controls and patients with BBL (p<0.001). In patients, resistin was significantly associated with tumor and inflammatory markers, cancer stage, tumor size, grade and lymph node invasion but not with anthropometric, metabolic parameters and hormone receptor status. Multivariable regression analysis revealed that serum IL-6 (p=0.02) and cancer stage (p=0.048) were the strongest determinants of serum resistin in cases adjusting for demographic, metabolic and clinicopathological features. Although resistin's diagnostic performance was low based on ROC curve analysis [0.72, 95% CI: 0.64-0.79], it could, however, represent a BC biomarker reflecting advanced disease stage and inflammatory state. CONCLUSION: Further prospective and longitudinal studies are needed to evaluate whether serum resistin could be used as a prognostic tool in BC monitoring and management. More research is essential to elucidate resistin's ontological role in the association between obesity, representing a chronic low-grade subclinical inflammation, and PBC.

Could serum visfatin be a potential biomarker for postmenopausal breast cancer?

OBJECTIVE: Previous studies have shown that visfatin is significantly elevated in patients with gastric carcinoma and postmenopausal breast cancer (PBC). We thus explored whether serum visfatin could be used as a potential diagnostic and prognostic tool for PBC, taking into account clinicopathological features, serum tumor markers, anthropometric and metabolic parameters. METHODS: Serum visfatin, tumor marker CA 15-3, carcinoembryonic antigen, metabolic and anthropometric parameters were determined in 103 postmenopausal women with pathologically confirmed, incident invasive breast cancer, 103 controls matched on age and time of diagnosis, and 51 patients with benign breast lesions (BBL). RESULTS: Mean serum visfatin was significantly higher in cases than in controls and patients with BBL (p<0.001). In cases, visfatin was significantly associated with CA 15-3 (p=0.03), hormone-receptor status (p<0.001), lymph node invasion (p=0.06) but not with metabolic and anthropometric variables (p>0.05). Multivariable regression analysis revealed that absence of estrogen and progesterone receptors (ER-PR-) was the strongest significant determinant of serum visfatin (p<0.001) in cases adjusting for demographic, metabolic and clinicopathological features. Based upon receiver operator characteristic analysis, serum visfatin outperformed CA 15-3 only in discriminating between PBC cases with early cancer stage than those with late stage, and in differentiating particularly patients with ER-PR- breast tumors. CONCLUSION: Further prospective and longitudinal studies are needed to determine whether serum visfatin could be used as a prognostic tool in the armamentarium of PBC monitoring and management in conjunction with other biomarkers.

Elevated serum visfatin/nicotinamide phosphoribosyl-transferase levels are associated with risk of postmenopausal breast cancer independently from adiponectin, leptin, and anthropometric and metabolic parameters.

OBJECTIVE: Obesity has been implicated in the etiology of postmenopausal breast cancer (PBC). We hypothesized that altered secretion of visfatin may underlie this association. We thus investigated the association of serum visfatin with PBC risk, taking into account known risk factors including adipokines and anthropometric and metabolic parameters. METHODS: In a case-control study, we studied 102 postmenopausal women with pathologically confirmed, incident invasive breast cancer and 102 control women matched on age and time of diagnosis between 2003 and 2010 at Army Share Fund Hospital, Veterans' Hospital (NIMTS). Levels of serum visfatin, adiponectin, leptin, metabolic parameters, carcinoembryonic antigen, and CA 15-3 were determined. RESULTS: The mean serum visfatin level was significantly higher in case than in control participants (P < 0.001). Women in the highest quartile of visfatin concentration presented significantly higher odds for PBC, adjusting for age, date of diagnosis, education, body mass index, waist circumference, years with menstruation, parity/age at first full-term pregnancy, breast-feeding, family history of cancer, use of exogenous hormones, alcohol consumption, smoking status, homeostasis model assessment score, and serum leptin and adiponectin concentrations (odds ratio, 7.93; 95% CI, 2.52-24.9). In case participants, the visfatin level correlated significantly with the tumor marker CA 15-3 (P = 0.03) but not with metabolic and anthropometric variables (P > 0.05). CONCLUSIONS: Further prospective studies are needed to determine whether an elevated serum visfatin level is implicated in the etiopathogenesis of PBC or reflects changes during PBC progression and could therefore be used as a biomarker for PBC.

Platelet markers correlate with glycemic indices in diabetic, but not diabetic-myelodysplastic patients with normal platelet count.

BACKGROUND: Altered thrombocyte morphology and function have been reported in patients with diabetes mellitus (DM) type 2. The aim of the present study was to determine the associations between platelet morphology markers and hemoglobin A1C (HbA(1c)), fasting glucose (FG), hypertension and coronary heart disease (CHD) in patients with myelodysplastic syndromes (MDS) and DM, in patients with DM and in controls. METHODS: This cross-sectional study included 30 cases with primary MDS with normal platelet count and non-insulin dependent diabetes, 30 non-insulin dependent diabetic patients and 30 non-diabetic, non-MDS controls matched on age and gender. RESULTS: After adjusting for body mass index, platelet number, CHD and hypertension, HbA(1c) and FG were significant predictors of mean platelet volume (MPV) and platelet distribution width (PDW) in diabetic patients. There was no correlation between platelet parameters and HbA(1c) or FG in diabetic MDS patients. In controls, FG and hypertension predicted significant differences in platelet morphology. Platelet count correlated with platelet morphology in diabetic MDS and control groups, but not in diabetics. CONCLUSIONS: MPV and PDW are associated with glycemic indices in diabetic patients but not in diabetic MDS patients with normal platelet counts. Non-diabetic controls also exhibit FG related changes in platelet morphology. This suggests other factors inherent to bone marrow dysplasia, platelet turnover and biochemistry, or vascular environment affect platelet morphology in diabetic MDS patients even with normal platelet count. Platelet morphology in this population may be an early marker for myelodysplasia. These findings also support platelet morphology change as a marker for elevated macrovascular disease risk.

B-cell chronic lymphocytic leukemia risk in association with serum leptin and adiponectin: a case-control study in Greece.

AIM: Leptin and adiponectin are two well-studied adipokines in relation to malignancies. In this study, we examined the association between leptin/adiponectin and risk of B-cell chronic lymphocytic leukemia (B-CLL), as well as the relationships between adipokines and several established prognostic factors of B-CLL. METHODS: Ninety-five patients with incident B-CLL and 95 hospital controls matched on age and gender were studied between 2001 and 2007, and blood samples were collected. Leptin, total and high molecular weight adiponectin, and prognostic markers of B-CLL were determined. RESULTS: Cases had a higher body mass index (BMI) than controls (p = 0.01) and lower levels of leptin (p < 0.01). Significantly more cases than controls presented a family history of lymphohematopoietic cancer (LHC) (p = 0.01). Higher serum leptin levels were associated with lower risk of B-CLL adjusting for age, gender, family history of LHC, BMI and serum adiponectin; the multivariate odds ratio comparing highest to lowest tertile was 0.05 (95% CI 0.01-0.29, p trend < 0.001); Adiponectin was not significantly different between cases and controls. CONCLUSION: Leptin was found to be inversely associated with risk of CLL but in contrast to prior studies of CLL and hematologic malignancies, this study found no significant association between CLL and adiponectin.

Low circulating adiponectin and resistin, but not leptin, levels are associated with multiple myeloma risk: a case-control study.

Accumulating evidence supports a role for obesity in the etiology of multiple myeloma (MM). The distinct possibility exists that obesity may be linked to MM through altered adipokine secretion and circulating levels, one of which, adiponectin, has a protective role in several malignancies, including leukemia. In this case-control study, we investigated the role of serum adiponectin, resistin, and leptin levels in the etiopathogenesis of MM and we explored their association with several established prognostic factors. Seventy three patients with incident, histologically confirmed MM and 73 controls matched on gender and age were studied between 2001 and 2007, and blood samples were collected. Serum adiponectin, leptin, resistin, as well as MM prognostic parameters were determined. Statistical analysis of the data was performed using univariate and multivariate analyses. Lower serum adiponectin and resistin levels were associated with higher risk of MM by bivariate analysis and after adjusting for age, gender, BMI, and serum levels of leptin (p < 0.0001). Adiponectin may have a protective role in MM, whereas leptin was not associated with risk for MM at a comparable level of significance and resistin levels may be decreased via a compensatory mechanism. Further studies are needed to confirm these associations and to explore the mechanisms underlying adiponectin's role in MM and plasma cell dyscrasias.

Is thyroid autoimmunity a risk factor for developing primary myelodysplastic syndrome?

OBJECTIVE: Thyroid disease has been associated with leukemia and lymphoma. No previous study using clinical and laboratory data has explored whether thyroid disease and especially autoimmune thyroid disease (ATD) is associated with myelodysplastic syndrome (MDS) risk. In this case-control study, we investigated the association of ATD with MDS. METHODS: Our study included 101 cases with incident primary MDS confirmed by histology and cytogenetics, and 101 controls matched on gender and age, admitted for non-neoplastic and non-infectious diseases. All subjects were submitted to clinical, ultrasound thyroid evaluation and serum free T3, free T4, TSH, thyroglobulin, and thyroperoxidase antibodies determination. RESULTS: Adjusting for age, gender, and body mass index, there was statistically significant evidence that ATD is associated with increased risk of MDS (OR = 2.58, 95% CI 1.29-5.16). Interestingly, ATD starting from the remote past (more than 10 years from MDS onset) was positively associated with MDS risk (OR = 5.73. 95% CI 2.03-16.16). Mean serum levels of fT3, fT4, and thyroid antibodies were significantly higher in MDS patients and mean TSH serum levels were significantly lower in MDS patients than in controls (p < 0.05). CONCLUSION: Biological plausibility and empirical evidence highlights the importance of ATD in MDS etiopathogenesis. Further studies are needed to explore underlying mechanisms associating thyroid autoimmunity with leukemogenesis.