Risk Factor Analysis Of Radiation Pneumonitis And The Gene Function Studies Of SIRT6 In A549 Cell Of Lung Cancer

OBJECTIVE:To investigate the risk factors of radiation pneumonitis(RP)in patients with non-small cell lung cancer(NSCLC)after thoracic radiation therapy and the gene function of SIRT6 in A549 cell of lung cancer.METHODS:1.A total of 153 patients with unresectable locally advanced NSCLC who underwent thoracic definitive radiation therapy at Shanghai Pulmonary Hospital were enrolled to analyze the risk factors of Grade?2 RP.2.Detected the expression of SIRT6 protein in NSCLC.The SIRT6 gene overexpression plasmid was constructed and transfected into lung cancer A549 cell by lentivirus infection.The effect of SIRT6 in A549 were investigated by cell proliferation,migration and cell cycle detection.And the effect of SIRT6 on the expression of apoptosis related proteins were also investigated by Western blot.RESULTS:1.17 patients(11.1%)were diagnosed with RP grade 2,15 patients(9.8%)were diagnosed with RP grade 3,and 1 patient(0.7%)were diagnosed with RP grade 5.Univariate analysis showed that pulmonary emphysema(PE)(P =0.012)and sub-clinical interstitial lung disease(sILD)(P <0.001)were associated with the occurrence of grade?2 RP.While sex,age,pathological type,smoking history and chemotherapy were not relative to the occurrence of grade?2 RP.Multivariate analysis showed that sILD was the independent risk factor for grade?2 RP(OR = 12.038,95% CI = 4.401-32.928,P <0.001).2.Western Blot showed that the expression of SIRT6 protein in NSCLC was lower than adjacent tissues.SIRT6 could effectively inhibit the migration and proliferation of A549 cells.Cell cycle test showed that SIRT6 could inhibit the S phase of A549 cells and prolong the G1 phase.The level of anti-apoptotic-related protein Bcl-2 in SIRT6 overexpression group was decreased after X-ray irradiation with 4Gy dose,while the levels of Bax and Cleaved caspase-3 proteins were increased.CONCLUSION:1.Emphysema and sub-clinical interstitial lung disease were associated with the occurrence of RP,but sub-clinical interstitial lung disease was the independent risk factors of grade?2 RP.2.SIRT6 can effectively inhibit the proliferation and migration of A549 cells,affect the cell cycles and leading to a shortened S phase but an extensional G1 phase.SIRT6 promotes cell apoptosis of A549 after irradiation.