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.

Trefoil factor 1 (TFF1) is a potential prognostic biomarker with functional significance in breast cancers.

Breast cancer (BC) is the most common cancer in women and the second leading cause of their cancer death. Establishing an accurate BC prognosis is very difficult because of its heterogeneity. Elevated TFF1 levels in serum were associated with development of BC, TFF1 expression was upregulated in BC compared to the healthy breast tissue. The aim of this study was to investigate the function of TFF1 in BCs, and to assess whether serum TFF1 could be used in formulating a prognosis for BC patients. In silico analyses were carried out to determine the expression of TFF1 mRNA in different types of BC and the association between TFF1 expression and survival of BC patients. Expression of TFF1 protein was checked in 52 paraffin-embedded tissues of BCs by immunochemistry, and serum concentration of TFF1 in 70 BC patients and 32 healthy controls was measured by ELISA. Functional activities of TFF1 in BC cells were determined by CCK-8 assay, colony formation, BrdU-DNA synthesis, and assays for migration and invasion. Results showed that expression of TFF1 mRNA was correlated with expression of biomarkers of luminal cancers including ESR1, GATA3, FOXA1, MYB and XBP1. In addition, patients with ER+BC had higher expression of TFF1 than those with ER- (p < 0.05). There was also lower expression of TFF1 in triple-negative breast cancer (TNBC) than in non-TNBC (p < 0.05), which corresponds with the level of serum TFF1 in TNBC patients, compared with non-TNBC patients (p < 0.001). Furthermore, expression of TFF1 was associated with tumor size (p = 0.002), nodal status (p < 0.001), histological grade (p < 0.001), ER status (p = 0.012), PR status (p < 0.001) and HER2 (p < 0.001), while serum TFF1 was only statistically different among BC with ER+, PR + and HER2+ (p = 0.04139, 0.0018, 0.0004). Elevated TFF1 expression correlated with increased overall survival of BC patients (p = 0.00068). Finally, TFF1 was found to inhibit the cell growth, colony formation, migration and invasion of BC cells in vitro. All these results suggest that expression of TFF1 was related to ER status of BC and that expression of TFF1 was lower in TNBC than in non-TNBC. TFF1 was found to inhibit proliferation, migration and invasion of BC cells in vitro. Expression of TFF1 was associated with clinical characters of patients with BC. Serum TFF1 could be used to predict prognosis of patients with BC, especially non-TNBC.

Serum TFF1 and TFF3 but not TFF2 are higher in women with breast cancer than in women without breast cancer.

Breast cancer remains a common malignancy in women, but the take-up for breast cancer screening programs in Japan is still low, possibly due to its perceived inconvenience. TFF1 and TFF3 are expressed in both breast cancer tissue and normal breast. Serum trefoil proteins were reported as cancer screening markers for gastric, prostate, lung, pancreatic cancer and cholangio carcinoma. The purpose of this study was to examine whether serum trefoil proteins could be screening biomarkers for breast cancer. Serum trefoil proteins in 94 breast cancer patients and 84 health check females were measured by ELISA. Serum TFF1 and TFF3 were significantly higher and serum TFF2 was significantly lower in breast cancer patients. Area under the curve of receiver operating characteristic of TFF1, TFF2, and TFF3 was 0.69, 0.83, and. 0.72, respectively. AUC of the combination of TFF1, TFF2, and TFF3 was 0.96. Immunohistochemically, TFF1 expression was positive in 56.5% and TFF3 was positive in 73.9% of breast cancers, while TFF2 was negative in all tumors. Serum TFF1 had positive correlation with expression of TFF1 in breast cancer tissue. Serum concentrations of TFF1 and TFF3 but not TFF2 are higher in women with breast cancer than in women without breast cancer.