Role Of Beclin1 And LC3 In Prognosis Of NSCLC Patients Receiving Postoperative Adjuvant Chemotherapy

Objective:To discuss the prognostic value of autophagy related protein Beclin1 and microtubule associated protein light chain 3 LC3 in patients with NSCLC(short for non-small cell lung cancer) who received postoperative platinum-based chemotherapy.Methods : Lung tissues of 50 and adjacent tissues of 20 patients who wereeventually diagnosed as NSCLC and were treated by surgery at The secondhospital affiliated to Dalian Medical University between 2008.1.1 and2012.12.31 were collected. All tissues came from patients with NSCLC who received at least three cycles of platinum-based postoperative adjuvant chemotherapy.Protein expressions of Beclin1 and LC3 in lung cancer tissues of50 NSCLC cases and in adjacent normal lung tissues of 20 cases were detected by immunohistochemisty.Collect the clinical data of the 50 patients andcall them to record the time when recurrence and metastasis or death due to lung cancer happened accurately. The Pearson χ2test was used to assess the association between Beclin-1 expression and several clinicopathologic variables. In an effort to determine whether the expression of these 2 proteins was correlated with a variety of clinicopathologic parameters, the Kaplan-Meier method was used to determine the probability of survival,and the data were analyzed via the log-rank test. Relationships between expressionsof two proteins with choice of chemotherapy and disease-free survival(DFS)time were analyzed.Results:(1)Positive expression rates of Beclin1(85% vs 52%) and LC3(90% vs46%) were significantly higher in adjuvant normal lung tissues than in lung cancer tissues with statistical differences(P=0.01,P=0.001).Expressions of Beclin1 was correlated with clinical stages,the later stages patients included more people with low expression of Beclin1,while the expressions of LC3 was correlated with clinical stages and differentiated degree. Expressions of two proteins were both not correlated with age,gender,cervical lymph node metastasis and pathological phenotype.(2)Expression of Beclin1 is positively associated with the expression of LC3,the correlation showed statistically significant(r=0.485,P=0).(3)Based on the results generated via the Kaplan-Meier method,smoking history,gender,PS score,lymph node metastasis, and the TNM stage were identified as the significant prognostic factors for NSCLC patients.(4) Patients in higher Beclin1 or LC3 expression group had longer DFS time than those in lower expression group(P=0.006,P=0.029);Patients with higher Beclin1 and LC3 expressions at the same time had longer DFS time than those with lower expressions(P=0.002).Conclusions : Autophagy related protein Beclin1 and Microtubule associated protein light chain 3 LC3 could effectively estimate prognosis of NSCLC patients receiving postoperative adjuvant chemotherapy. Lower Beclin1 and LC3 expression may be predictor of patients with NSCLC who have adverse outcomes after postoperative adjuvant chemotherapy.The deficiency of autophagy may be involved in the NSCLC tumorigenesis and tumor progression,it may be the new treatment strategies for NSCLC in the future.