Increased PARP Activity and DNA Damage in NSCLC Patients: The Influence of COPD

SIMPLE SUMMARY: Many people still die of lung cancer (LC), a disease that is mainly related to cigarette smoking. Smokers may also develop chronic obstructive pulmonary disease (COPD). COPD is a risk factor per se for LC. Cigarette smoking and other chemicals injure DNA on a daily basis. A repair mechanism based on PARP-1 and PARP-2 activity can restore damaged DNA to keep cells alive. However, cancer cells also take advantage of this mechanism to survive. Fifteen LC-COPD and 15 LC patients were enrolled in this study to elucidate whether COPD influences DNA damage-dependent PARP activity in lung tumors. DNA damage, PARP activity, PARP-1 and PARP-2 expression were analyzed in tumor and non-tumor lungs obtained during surgical resection of the lung tumors. DNA damage and PARP activity were increased only in tumors in LC-COPD patients. However, PARP-1 and PARP-2 expression decreased in tumors of both patient groups. LC patients with COPD may benefit from PARP inhibitor therapies. ABSTRACT: (1) Background: Lung cancer (LC) is a major leading cause of death worldwide. Poly (ADP-ribose) polymerase (PARP)-1 and PARP-2 are key players in cancer. We aimed to assess PARP-1 and PARP-2 expression and activity and DNA damage in tumors and non-tumor lungs from patients with/without chronic obstructive pulmonary disease (COPD). (2) Methods: Lung tumor and non-tumor specimens were obtained through video-assisted thoracoscopic surgery (VATS) in LC patients with/without underlying COPD (two groups of patients, n = 15/group). PARP-1 and PARP-2 expression (ELISA), PARP activity (PARP colorimetric assay kit) and DNA damage (immunohistochemistry) levels were identified in all samples. (3) Results: Both PARP-1 and PARP-2 expression levels were significantly lower in lung tumors (irrespective of COPD)compared to non-tumor specimens, while DNA damage and PARP activity levels significantly increased in lung tumors compared to non-tumor specimens only in LC-COPD patients. PARP-2 expression was positively correlated with smoking burden in LC-COPD patients. (4) Conclusions: In lung tumors of COPD patients, an overactivation of PARP enzyme was observed. A decline in PARP-1 and PARP-2 protein expression was seen in lung tumors irrespective of COPD. Other phenotypic features (airway obstruction) beyond cancer may account for the increase in PARP activity seen in the tumors of patients with underlying COPD.