Increased PARP Activity and DNA Damage in NSCLC Patients: The Influence of COPD.
Jun TangVíctor CurullXuejie WangCoral AmpurdanésXavier DuranLara PijuanAlberto Rodríguez-FusterRafael AguilóJosé YélamosEsther BarreiroPublished in: Cancers (2020)
(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.
Keyphrases
- dna damage
- dna repair
- chronic obstructive pulmonary disease
- end stage renal disease
- oxidative stress
- chronic kidney disease
- ejection fraction
- newly diagnosed
- lung function
- poor prognosis
- peritoneal dialysis
- small cell lung cancer
- mass spectrometry
- minimally invasive
- nitric oxide
- squamous cell carcinoma
- acute coronary syndrome
- young adults
- binding protein
- single cell
- simultaneous determination
- sensitive detection