TGF-β1, IL-6, and TNF-α in bronchoalveolar lavage fluid: useful markers for lung cancer?

Abstract

Changes of cytokines in bronchoalveolar lavage fluid (BALF) reflect immunologic reactions of the lung in pulmonary malignancies. Detection of biomarkers in BALF might serve as an important method for differential diagnosis of lung cancer. A total of 78 patients admitted into hospital with suspected lung cancer were included in our study. BALF samples were obtained from all patients, and were analyzed for TGF-β1, IL-6, and TNF-α using commercially available sandwich ELISA kits. The levels of TGF-β1 in BALF were significantly higher in patients with lung cancer compared with patients with benign diseases (P = 0.003). However, no significant difference of IL-6 (P = 0.61) or TNF-α (P = 0.72) in BALF was observed between malignant and nonmalignant groups. With a cut-off value of 10.85 pg/ml, TGF-β1 showed a sensitivity of 62.2%, and a specificity of 60.6%, in predicting the malignant nature of pulmonary disease. Our data suggest that TGF-β1 in BALF might be a valuable biomarker for lung cancer. However, measurement of IL-6 or TNF-α in BALF has poor diagnostic value in lung cancer.

Figure 1. Comparison of TGF-β1, IL-6, and TNF-α levels in bronchoalveolar lavage fluid between benign and malignant groups.

The levels of TGF-β1 were significantly higher in lung cancer patients than those in benign diseases (P = 0.003, Mann-Whitney U-test) (A); no significant difference of IL-6 (P = 0.61, Student's t-test) (B) or TNF-α (P = 0.72, Student's t-test) (C) levels was found between malignant and nonmalignant groups. Horizontal lines represent the median values for TGF-β1; Horizontal lines represent the mean values for IL-6 and TNF-α.

Figure 2. Correlation of TGF-β1, IL-6, and TNF-α levels in bronchoalveolar lavage fluid.

Statistically correlation was observed between TGF-β1 and IL-6 (r = 0.337, P = 0.003) (A); no significant correlation was found between TGF-β1 and TNF-α (r = 0.121, P = 0.290) (B) or between IL-6 and TNF-α (r = −0.022, P = 0.847) (C).

Figure 3. Receiver operating characteristic (ROC) curve was performed to evaluate the threshold value of TGF-β1 in differentiating malignant from benign pulmonary diseases.

TGF-β1 reached a sensitivity of 62.2%, a specificity of 60.6%, a positive predictive value of 67.5%, and a negative predictive value of 52.6% (cut-off value: 10.85 pg/ml; area under the curve: 0.695).