Diagnostic value of neurotrophin expression in malignant pleural effusions

Abstract

Abstract. Neurotrophins (NTs) modulate the growth of human malignancies, including lung cancers. Our prospective study evaluated the accuracy of pleural NTs [nerve growth factor, brain-derived neurotrophic factor (BDNF), neurotrophin 3 (nT3) and 4 (nT4)] levels for differentiating benign from malignant pleural exudates. Levels of NTs were measured by ELISA in 170 patients with non-neutrophilic (<50%) exudative benign or malignant pleurisies diagnosed by pleuroscopy. Fifty-nine benign (9 infections and 50 inflammatory diseases) and 111 malignant (50 extrathoracic tumors, 51 lung cancers and 10 mesotheliomas) pleural exudates were diagnosed by thoracoscopy. Levels of BDNF were significantly higher in malignant than in benign effusions [17 pg/ml (0-367) vs. 8 pg/ml (0-51), p<0.05]. ROC analysis showed an area under the curve of 0.609 (p=0.012; best threshold 44 pg/ml). Pleural BDNF levels were significantly higher in pleural metastasis of pulmonary tumors and in mesothelioma than in pleural benign effusions. Finally, a higher proportion of pleural nT3 was detected in squamous cell lung carcinoma in comparison to that in nonsquamous cell lung carcinoma (72.7 vs. 10%, p<0.0001). NTs and particularly BDNF may play a role in the pathogenesis of malignant pleural effusions.

Brain-derived neurotrophic factor, a new soluble biomarker for malignant pleural mesothelioma involved in angiogenesis

“…These results confirmed a preliminary observation by Duysinx and colleagues performed on only 10 MPM PE [ 4 ] and can be explained, in part, by the ability of MPM cells to produce high level of BDNF (Additional file 6 : Figure S3C). This growth factor can also be produced by a large variety of cells [ 5 ] explaining its presence in other PE, but at a lower amount.…”

“…1d and Additional file 4 : Table S2). BDNF was already described as overexpressed in several other cancers [ 4 ]. In TCGA cohort, we observed that MPM has the highest BDNF expression among 37 tumor types indicating that BDNF gene overexpression is a hallmark of MPM (Fig.…”

“…In several cancers, BDNF was described as overexpressed in the tumor environment [ 4 , 7 ] and can be associated with poor survival [ 8 ]. Then, we evaluated the prognosis value of BDNF in MPM PE.…”