RESPIRATORY MUSCLE STRENGTH, EXERCISE CAPACITY, AND DYSPNEA DURING PULMONARY REHABILITATION AFTER LOBECTOMY IN PATIENTS WITH NON-SMALL CELL LUNG CANCER

Background and Aims: Lung cancer is the leading cause of cancer-related mortality worldwide. Most patients are diagnosed at an advanced stage without noticeable symptoms. Nicotine, as the major addictive component in cigarettes, may be involved in the progression of lung cancer cells after a long term exposure. The present study investigates the potential effectors of long-term nicotine exposure in lung cancer. Methods: cDNA microarray was firstly used to explore the potential effectors of long-term nicotine exposure in the parental squamous lung cancer cells, H157, and H157N, harvested with nicotine (10 μM) for 2 years. The bioinformatics platform was used to analyze whether the mRNA expression of various effectors might contribute to patient survival. Results: There were 5 transcripts (CXCR4, VEGFA, TP73, IL-1β, WNT5A) (>2-fold intensity) were significantly increased and associated with several pathways (i.e. Activation of MAPK activity, positive regulation of protein phosphorylation, response to hypoxia and ion transport). Accordingly, the Kaplan–Meier survival curves of patient groups with CXCR4, VEGFA, TP73 and IL-1β significantly predicted a worse overall survival of lung cancer patient. Intriguingly, high WNT5A mRNA levels improved patient survival in 1926 lung cancer cases (P = 0.003) but unexpectedly associated with a poor survival rate in those patients with smoking history (P = 0.005). Conclusion: Our results suggested that the interplay of long term nicotine exposure and WNT5A related signalling might play roles in lung cancer. The exact roles and underlying mechanisms of the WNT5A related signalling as well as its interplay with nicotine demand further investigations in particular those lung cancer patients with smoking history.