Prognosis Significance Of Tumor-associated Neutrophils And Peripheral Neutrophil-lymphocyte Ratio In Patients With Non-small Cell Lung Cancer

Background:Lung cancer is the highest morbidity and mortality of malignant tumors in China.It is also one of the most common malignant tumors and the leading cause of cancer-related death in worldwide;among them,non-small cell lung cancer(NSCLC)accounted for about 85%of the total number of lung cancer.Despite the progress of operation,radiotherapy and chemotherapy,especially targeted therapy,the survival prognosis of NSCLC patients has been improved,but the overall prognosis is still poor.The 5 year survival rate is only 15%.Therefore,it is important to explore and clarify the related factors that affect the prognosis of NSCLC patients.In recent years,studies have shown that inflammation is closely related to the occurrence and development of malignant tumors.Neutrophils,one of the important components of inflammatory cells,have been proved to play an important role in the development of tumor.The neutrophil infiltrating tumor,also known as tumor associated neutrophils(TANs),is closely related to the prognosis of many tumor patients.In hepatocellularcarcinoma,renal cancer and other tumors,the increase of TANs infiltration indicates that the survival of patients is worse.In colorectal cancer research,TANs is highly infiltrated and has a longer overall survival.The inconsistency of these results may be related to the different localization and function of TANs in the tumor.TANs in tumor nests and stroma can differentiate into anti-tumor N1 or tumor-promoting N2 under the influence and regulation of tumor cells,mesenchymal cells(mainly fibroblasts),etc.,thereby further affecting tumor development and Patient prognosis.At present,there are few studies on the relationship between the distribution of TANs in the tumor locality and the prognosis of patients with non-small cell lung cancer.The neutrophil-lymphocyte ratio(NLR)in peripheral blood has been proved to have a predictive effect on the prognosis of many cancer patients including NSCLC,which is an economical and convenient indicator.However,the correlation with TANs in tumors in NSCLC is not yet clear.Objective:This study was designed to systematically investigate the distribution and number of local TANs,and the correlation between peripheral blood NLR and clinicopathological features of patients with NSCLC,in particular their survival prognosis(overall survival(OS)and disease-free survival(DFS))and analyze the correlation between TANs and NLR,in order to judge the prognosis of NSCLC provides reliable and economic forecasting index.Method:The basic data and pathological specimens of 133 patients with non-small cell lung cancer who were diagnosed in the Department of Chemotherapy and Thoracic Surgery of Qilu Hospital of Shandong University from January 2009 to December 2010 were collected.The tumor associated neutrophils were detected by immunochemistry.The relation of patients sex,age,history of smoking,pathological type,histological grade,TNM stage and lymphonote metastasis with NLR in peripheral blood and TANs was analyzed by chi-square test.Kaplan-Meier curves and Cox univariate and multivariate survival analyses were used to investigate the relationship between the patients’clinicopathological features and OS and DFS respectively.Subgroup analysis was used to analyze the significance of stromal TANs in patients with different pathological types and TNM staging.Result:1.TANs were detected in tumor nests and stroma of NSCLC.The average density in tumor nests was 11.51,and the average density in stroma was 16.23.2.Chi-square analysis results showed that the density of introtumoral TANs was significantly associated with TNM stage,pathological type and differentiation degree,and the density of stromal TANs was significantly associated with smoking history,TNM stage and differentiation degree.3.Using the ROC curve,the cutoff value of TANs in tumor nests was 8.33.The survival analysis showed that the density of TANs in tumor nests was an positive prognostic factor of OS(P=0.004);the stromal TANs had a cutoff value of 11.00,太the stromal TANs was an positive prognostic factor of OS(P=0.001);TNM staging(P<0.001)and lymph node metastasis(P = 0.018)were significant factors in the clinicopathological factors of patients with OS;4.For the operative patients,using the ROC curve,the TANs cutoff value of the tumor nest was 7.50,and the cutoff value of the stromal TANs was 29.50.The survival analysis results showed that the density of tumor nests and stromal TANs had no significant influence on the patients’ DFS;In pathological features,lymph node metastasis suggested a shorter DFS in patients(P=0.041).5.The NLR in peripheral blood was significantly associated with TNM staging and pathological types.NLR levels had a significant effect on OS and DFS.The higher NLR levels In peripheral blood suggested worse prognosis.6.There was no significant correlation between intromal TANs and stromal TANs and NLR levels in peripheral blood.Conclusion:Studies have shown that patients with large non-small cell lung cancers with introtumoral and stromal TANs have longer OS;in multivariate analysis,TANs did not suggest an independent prognostic factor for OS.High levels of peripheral NLR are significantly associated with poor prognosis,but there is no significant correlation between NLR and TANs,and NLR is susceptible to other factors,so TANs are more reliable as indicators of prognosis.