Abstract
Chronic obstructive pulmonary disease (COPD) patients are at higher risk of developing lung cancer and its metastasis, but no suitable biomarker has been reported for differential diagnosis of these patients. Levels of serum biomarkers (VEGF, IL-8, MMP-9 and MMP-2) were analyzed in these patients, which were compared with healthy donors (HD). Levels of VEGF (P < 0.005) and MMP-9 (P < 0.05) were significantly higher in COPD patients than HD. Compared to HD, a decrease in IL-8 (~8.1 folds; P < 0.0001) but an increase in MMP-9 (~1.6 folds; P < 0.05) levels were observed in the lung cancer patients. Cancer patients showed significantly (P < 0.005) lower levels of serum VEGF (1.9 folds) and IL-8 (~9 folds) than the COPD patients. VEGF level was significantly higher (2.6 folds; P < 0.0005) in metastatic than non-metastatic cancer patients. However, MMP-2 didn’t show significant variation in these patients. The Youden’s index (YI) values for lung cancer diagnosis in HD using IL-8 was 0.55 with 83.3% overall accuracy. VEGF was able to diagnose COPD in HD with better YI (0.38) and overall accuracy (70.6%). IL-8 was able to diagnose cancer in COPD patients and HD with YI values of 0.35, 0.55 with 71% and 83.3% overall accuracy, respectively.
Highlights
In lung cancer patients with chronic obstructive pulmonary disease (COPD) was significantly lower than patients with normal pulmonary function (77% versus 91.6%) due to higher recurrence rate[10]
Levels of vascular endothelial growth factor (VEGF), IL-8, matrix metallo-protease-9 (MMP-9) and matrix metallo-protease-2 (MMP-2) were measured in serum samples of COPD and lung cancer patients, which were compared with HD (Figs 1 and 2, Table 1)
In the two COPD patients, who were incidentally diagnosed with lung cancer metastasis, the levels of these serum biomarkers were determined [VEGF (2658.0, 1013.5 pg/ml), IL-8 (11.8, 23.7 pg/ml), MMP-9 (661.8, 1166.7 ng/ml) and MMP-2 (209.2, 95.7 ng/ml)]
Summary
In lung cancer patients with COPD was significantly lower than patients with normal pulmonary function (77% versus 91.6%) due to higher recurrence rate[10]. Being radiation based and costly technique, routine use of computed tomography for mass screening of patients is rather impractical and unaffordable, especially in developing countries like India In this direction, the potential of biomarkers (e.g. circulating DNA in peripheral blood, circulating tumor-derived exosome, micro-RNAs, comparative protein profiling) in lung cancer diagnosis has been discussed and reviewed[14]. In this regard, developing suitable biomarkers for early diagnosis of lung cancer/its metastasis in COPD patients, may help for lung cancer surveillance and better management of the disease In this regard, our previous study in human lung cancer cells (A549) showed role of autocrine cytokines [vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), matrix metallo-protease-2 (MMP-2)] in the process of epithelial-to-mesenchymal transition and associated metastatic features[18,19]. This study is a further attempt to distinguish lung cancer (metastatic and non-metastatic) and COPD conditions by assaying serum levels of these analytes
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