Circulating tumor cells in peripheral and pulmonary venous blood predict poor long-term survival in resected non-small cell lung cancer patients

Zhong Chen,Yunsong Li,Shaofa Xu,Yi Liu,Zhidong Liu,Xu Cheng

doi:10.1038/s41598-017-05154-x

Abstract

We tested the hypothesis that circulating tumor cells (CTCs) in preoperative peripheral blood (PPB) and intraoperative pulmonary venous blood (IPVB) could predict poor long-term survival in resected non-small cell lung cancer (NSCLC) patients. CTCs were separated from blood using magnetic beads coated with antibodies against epithelial-cell adhesion molecule (EpCAM) via magnetic-activated cell sorting (MACS). CTCs were quantified with fluorescence-labeled antibodies against pan-cytokeratin through flow cytometry. CTCs were quantified in PPB and IPVB in 23 consecutive stage I-IIIA patients with resected NSCLC. The association between CTCs and prognosis in these patients was evaluated after a 5-year follow-up. In NSCLC patients, outcomes were assessed according to CTC levels at surgery. NSCLC patients identified as high-risk groups exhibited >5 CTCs/15 mL in PPB and >50 CTCs/15 mL in IPVB. Univariate Cox proportional-hazards regression analysis showed that the CTC count in PPB or IPVB was an independent risk factor for tumor-free surivival (TFS) and overall survival (OS). The high-risk group of patients had a shorter median TFS (22 months vs. >60.0 months, p < 0.0012) and shorter OS (27 months vs. >60 months, p < 0.0015). The number of CTCs counted in PPB and IPVB was an independent risk factor for TFS and OS in resected NSCLC patients.

Highlights

Non-small cell lung cancer (NSCLC) is one of the most aggressive malignant tumors with the highest morbidity and mortality worldwide
The average (±SD) age of the patients was 61.7 ± 9.5 years; 52.2% of the patients presented with squamous carcinoma, 47.8% of the patients presented with adenocarcinoma, and 26.1% of the patients presented with lymphnode metastasis
We tested the hypothesis that tumor cells of stage I-IIIA non-small cell lung cancer (NSCLC) patients were able to spread to the entire body via pulmonary and peripheral venous blood vessels and identified the relationship between circulating tumor cells (CTCs) and poor long-term survival in surgically resected NSCLC patients

Summary

Introduction

Non-small cell lung cancer (NSCLC) is one of the most aggressive malignant tumors with the highest morbidity and mortality worldwide. Surgical resection is the preferred comprehensive treatment for stage I-IIIA NSCLC; postoperative metastases and recurrence still occur in early-stage cancer patients, even reaching approximately 29% in stage I patients[1]. Early-stage NSCLC patients have different prognoses, and the progression of disease is primarily due to micro- or occult metastasis and recurrent tumors[2]. No clinical imaging or other technology can sensitively detect early and micro- or occult metastases in these lung cancer patients[3, 4]. Once metastasis or recurrent cancer are clinically observed, the tumors are quite large and difficult to treat, and the patients have lost the best time window for effective therapy. Recent technological advances regarding the detection of circulating tumor cells (CTCs) in the blood of cancer patients could fill the gap in clinical diagnostics. A 5-year follow-up study was conducted to identify the association of long-term survival with CTC counts in these patients to establish a clinical diagnostic intervention for future large-scale clinical trials[13]

Methods

Results

Conclusion