Investigation of biomarkers for pulmonary carcinomatous lymphangitis in patients with lung cancer

Introduction: It is a crucial issue to perform differential diagnosis on the newly emerging interstitial opacities with dyspnea in the advanced lung cancer patients during chemotherapy. Many possible causes of these image findings should be considerd, such as interstitial pneumonia including drug-induced, infections, and pulmonary carcinomatous lymphangitis (PCL). The treatments for these diseases are different from each other, but urgent matters. Aim: To establish biomarkers for PCL of lung cancer. Method: Serum samples are collected from the subjects, which includes patients with lung cancer with lymphangitis (Lym, n=7), with enlarged lymph nodes (LCN, n=4), without lymphangitis or enlarged lymph nodes (LC, n=7), interstitial pneumonia (IP, n=8), infectious pneumonia (Inf, n=8), and healthy volunteers (Cnt, n=13). We measured serum VEGFR3, VEGF-C, and Lyve-1, which are important receptors and a ligand for lymphangiogenesis, by ELISA. We also measured CRP, KL-6, and SP-D. Statistics were performed by ANOVA and post-hoc analysis. Result: Serum VEGF-C and Lyve-1 were not different among these groups. Serum VEGFR3 levels were higher in LCN and in Cnt compared with Lym. CRP levels were significantly increased in Inf than that in several other groups. KL-6 and SP-D levels were significantly increased in Lym and IP than other groups. However, any marker could not be useful for PCL by itself. KL-6/SP-D is significantly higher in Lym than that in the others. Conclusion: Although three molecules regarding to lymphangiogenesis were not useful for the diagnosis of PCL in patients with lung cancer, KL-6/SP-D may be a promising biomarker for PCL.