Circulating trefoil factors in relation to lung cancer, age and lung function: a cross-sectional study in patients referred for suspected lung cancer.

The trefoil factor family proteins: TFF1, TFF2 and TFF3 are secreted by epithelial cells in the respiratory tract. Here, we explore circulating concentrations of the trefoil factors in relation to lung cancer, age and lung function. We included 751 patients suspected of lung cancer. Lung cancer diagnosis was based on data reported to a national database. Serum TFF1, TFF2 and TFF3 concentrations were measured by ELISA, and spirometry was performed within ±3 days of blood sampling. Forced expiratory volume in the first second (FEV1) in relation to forced vital capacity (FVC), FEV1/FVC (a parameter used to quantify reduced lung function) was recorded. Lung cancer was diagnosed in 163 (22%) patients. Circulating concentrations of TFF3 (p = .021), but not TFF1 and TFF2, were significantly elevated in cancer patients. All three trefoil factors showed an increase in concentration with increasing age (p < .001) and declining lung function (p < .004). In the present cohort, concentrations of all three peptides were elevated compared with previous results published for healthy individuals. In conclusion, we report higher concentrations of TFF3 in patients with lung cancer, while increasing age and reduced lung function are associated with increasing concentrations of all trefoil factors in this specific patient population. The results emphasize that age and lung function should be taken into consideration when evaluating concentrations of trefoil factors in patients. However, the increases in trefoil factor concentrations were relatively small, and consequently, it is unlikely that circulating trefoil factor concentrations may have a role in the diagnosis of lung cancer and lung function impairment.

Neutrophil-lymphocyte-ratio distributions in a Danish population from general practice.

The neutrophil-lymphocyte ratio (NLR) is a novel biomarker, showing promising both diagnostic and prognostic capabilities. The aim of this study was to present NLR distributions in a Danish population from general practice (GP) and compare levels between patients from intensive care units (ICU) and GP. A register-based study was conducted using results from 31,966 blood samples from GP and ICU located in the admission area of Aarhus University Hospital, Denmark. Exclusion of samples with lymphocytes >40 × 109/L, resulted in 28,582 samples from GP and 3,373 from ICU. Distributions for patients from GP with CRP <8 mg/L were age-dependent and were established for the following three age groups; 0-17 years [0.30:3.76], 18-75 years: [0.74:4.94], above 76 years: [0.89:8.80]. Patients from ICU had a significantly higher median NLR than patients from GP when stratified for CRP, [8.48 and 1.99 respectively]. This study describes for the first time the distributions of NLR in a large European population of GP patients.

Trefoil factor peptide 3 is positively correlated with the viscoelastic properties of the cervical mucus plug.

INTRODUCTION: The viscoelastic properties of the cervical mucus plug are considered essential for the occlusion of the cervical canal and thereby for protection against ascending infections during pregnancy. Factors controlling this property are virtually unknown. This study explores a possible role of trefoil factor peptides 1, 2 and 3 (TFF1-3); peptides believed to influence mucus viscosity. MATERIAL AND METHODS: The study is based on spontaneously shed cervical mucus plugs from 14 women in active labor. The viscoelastic properties; the elastic modulus (G') and the viscous modulus (G") were determined by an oscillatory rheometer. The concentrations of TFF1-3 were measured by an in-house enzyme-linked immunosorbent assay. Associations were analyzed by random-effects generalized least-squares regression analyses. RESULTS: Median (range) concentrations of TFF1, TFF2 and TFF3 were 3.1 (1.2-8.6), 1.1 (<0.006-3.7) and 1000 (170-5300) nmol/g cervical mucus plug, respectively. The TFF3 concentration was associated with G' (regression coefficient 11.7 Pa/Log nm; 95% CI 3.0-20.4, p = 0.009) and G" (regression coefficient 3.2 Pa/Log nm; 95% CI 1.5-5.0, p < 0.001). CONCLUSION: We suggest that TFF3 plays a role in the viscoelastic properties of the cervical mucus plug.

Validation of commercial assays for measurements of trefoil factor family peptides in serum.

BACKGROUND: Trefoil peptides (TFF1, TFF2 and TFF3) are 7-12 kDa molecules, secreted by mucin-producing epithelial cells. Increased serum concentrations have been reported in a number of pathological conditions, which warrants the need for validated commercially available assays. METHODS: We validated commercial assays for TFF1-3 and compared results obtained with our in-house assays, using serum from blood donors. RESULTS: Level of detection was: ≤ 0.008 nmol/L. Measuring ranges were: 0.032-0.51 (TFF1), 0.038-0.76 (TFF2) and 0.019-0.15 (TFF3) nmol/L. Imprecision (CV), judged from the measurement of serum pools in two levels, was below 9% (TFF2 and TFF3) but up to 18% (mean 0.41 nmol/L) for TFF1. No cross reactivity between the TFFs (concentrations > 100 nmol/L) was observed. The 95% non-parametric reference intervals were: <0.0032-0.53 (TFF1), 0.099-1.4 (TFF2) and 0.086-0.87 (TFF3) nmol/L. Comparing commercial to in-house assays (n=132), showed biases explained by differences in the calibrators (TFF1 and TFF2). A number of samples showed markedly different results. CONCLUSIONS: The commercial assays for TFF2 and TFF3 are acceptable for use on serum samples, while the TFF1 assay revealed a poor imprecision and a too narrow measuring range. Results obtained with the commercial and the in-house assays differed, partly because of differences in the calibrators employed.

Trefoil factor family peptides in the human foetus and at birth.

BACKGROUND: Trefoil factors (TFF1-3) are cysteine-rich peptides secreted by mucosal surfaces. Changing levels of expression are reflected in serum concentrations. Serum levels of TFF2 and TFF3 are highly elevated during pregnancy. Here, we explore a possible foetal origin of these increased levels. MATERIALS AND METHODS: We examined the expression of trefoil peptides in foetal tissues, placentas and foetal membranes from midterm abortions by immunohistochemistry. Employing in-house ELISAs, serum concentrations of TFF1-3 were measured in 92 paired samples of cord and maternal blood prior to delivery. Size exclusion chromatography was used to investigate the molecular forms of TFF1-3. RESULTS: Immunohistochemistry showed all trefoil peptides to be present during foetal life, but compared to adults with a more widespread expression of TFF2 and TFF3 in the stomach and Brunner's glands. No trefoil peptides were seen in placentas or foetal membranes. Median serum concentrations of TFF1 in cord blood were comparable to those observed in the (mother) [0·42 (0·37) nM, P = 0·25], whereas TFF2 and TFF3 showed lower values than in the mother [0·11 (0·69), and 1·2 (6·7) nM, respectively, P < 0·0001 for both peptides]. Size exclusion chromatography showed comparable patterns in mothers and newborns. CONCLUSIONS: All three trefoil peptides are expressed in foetal tissues but not in placenta or foetal membranes. Cord blood contains high levels of all three peptides, although for TFF2 and TFF3 at considerably lower levels than observed in the mother. Thus, the elevated serum levels of TFF2 and TFF3 in the pregnant women were most likely not of foetal origin.