Correlation Between Circulating Tumor Cells In Peripheral Blood And Recurrence And Metastasis In Postoperative Patients With Non-Small Cell Lung Cancer

Background and ObjectiveLung cancer is the leading cause of cancer-related deaths in men and women worldwide.According to the pathological classification criteria,lung cancer is mainly divided into two categories: small cell lung cancer(SCLC)and non-small cell lung cancer(NSCLC).NSCLC accounts for about 85% of lung cancer patients,most of which are diagnosed at the advanced stage of cancer with high degree of malignancy and poor prognosis.Despite the accelerated improvement of multiple treatment methods such as surgery,radiotherapy,chemotherapy,targeted therapy and immunotherapy,the 5-year survival rate of lung cancer is still less than 20%,and it is a serious threat to human health.In recent years,with the improvement of people’s living standards and health awareness,the concept of regular physical examination has been strengthened,so as to improve the early detection rate and operation rate of lung cancer.However postoperative recurrence and metastasis is still the leading cause of high mortality rate in patients with non-small cell lung cancer.Regular monitoring,early detection and early intervention should be conducted on patients with non-small cell lung cancer after surgery to improve the 5-year survival rate and prolong the survival period of patients with lung cancer.At present,follow-up of postoperative patients with lung cancer often adopts the method of combining tumor markers and imaging examination,which is difficult to detect micro-metastatic lesions and easy to delay the optimal treatment opportunity.The circulating tumor cells(CTCs)are the malignant tumor cells that enter the peripheral blood circulation after shedding from the primary tumor tissues or metastases.They have the same characteristics and genes of primary tumor and are the key factors for distant metastasis of tumors.Researches have shown that peripheral blood CTCs can predict tumor recurrence at least several months earlier than imaging progression.The Food and Drug Administration(FDA)has approved the Cellsearch system based on the positive selection of epithelial cell adhesion molecule(EpCAM)for detecting the number of circulating tumor cells in peripheral blood of patients with prostate cancer,breast cancer,non-small cell lung cancer and colorectal cancer.But the tumor EpCAM on the cell surface is down-regulated during the epithelial-mesenchymal transition,epithelial antigens are progressively deleted,and turn to express mesenchymal phenotypes.EpCAM-based enrichment is limited to epithelial CTC detection,and the CTCs with mesenchymal phenotype cannot be detected,thereby reducing the sensitivity of detection.At the same time,due to its high cost,it is difficult to be widely used in clinical practice.In this paper,we use the Isolation by size of epithelial tumor cell(ISET)technology to detect the number of circulating tumor cells in patients with non-small cell lung cancer after surgery,so as to study the feasibility of predicting recurrence and metastasis of patients with lung cancer after surgery.MethodWe retrospectively evaluated 40 NSCLC patients undergoing CTCs test with the ISET technology within one month ± five days after surgery in the First Affiliated Hospital of Zhengzhou University from January 2016 to December 2018.Demographics,surgical time,surgical methods,pathological types,pathological staging,imaging findings,CTC counts,presence or absence of recurrence and time to relapse were collected.The number of CTCs in peripheral blood more than or equal to 5 per 7.5mL was defined as CTCs positive,and CTC less than 5 per 7.5mL was defined as CTCs negative.Risk stratification was performed according to CTC positive and CTC negative to study the predictive effect of CTC on postoperative recurrence and metastasis in patients with non-small cell lung cancer.Statistical analysis was performed using SPSS 21.0 software.Kaplan-Meier method was used for single factor analysis of pathological type,pathological stage,CTC,CTM,etc.,then meaningful indicators were selected.Cox regression model was used for multivariate analysis to screen out independent risk factors for recurrence and metastasis of NSCLC,and P<0.05 was considered to be statistically significant.Results1.40 NSCLC patients with stage I-III were reviewed in one month after operation.CTCs were detected in peripheral blood by ISET technique.There were 25 cases of CTCs positive patients and 15 cases of CTCs negative patients,with a positive rate of 62.5%.2.Circulating tumor microemboli(CTM)was only detected in CTCs positive patients.A total of 8 CTCs positive patients was detected CTM with a positive rate of 20%.All CTM positive patients had recurrence and metastasis after surgery.The median DFS of CTM positive patients was 17.2 months.While the median DFS of CTM negative patients was not reached.3.Univariate analysis showed that CTC positive,CTM positive,pathological stage,and lymph node metastasis were correlated with recurrence and metastasis in NSCLC patients after surgery,while gender,age,surgical procedure,smoking history,and pathological type were not correlated with postoperative recurrence and metastasis of patients with NSCLC.4.Multivariate analysis showed that CTC positive and pathological stage were independent factors influencing postoperative tumor recurrence and metastasis in patients with NSCLC.Conclusion1.Circulating tumor cell counts can be used as an effective indicator for predicting postoperative recurrence and metastasis in patients with non-small cell lung cancer.CTC-positive patients are associated with shorter disease-free survival.2.ISET technology has certain feasibility in detecting peripheral blood circulation tumor cells in patients with non-small cell lung cancer.