Detection of CTCs and CSCs in the staging and metastasis of non-small cell lung cancer based on microfluidic chip and the diagnostic significance.
Author(s): Wang SQ, Shuai ZF, Zhang XJ, Wu T, Dong HY, Liu T, Wen QT, Yu XW
Publication: Eur Rev Med Pharmacol Sci, 2020, Vol. 24, Page 9487-9496
PubMed ID: 33015791 PubMed Review Paper? No
Purpose of Paper
This paper compared the sensitivity and specificity of detecting circulating tumor cells (CTCs) in peripheral blood from non-small cell lung cancer (NSCLC) patients using a microfluidic chip device to the CellSearch System. Correlations between patient age, gender, tumor classification, clinical stage, presence of metastases, treatment status, and serological tumor markers and CTC and cancer stem-like cell (CSC) positivity rates as determined by microfluidic chip were also examined.
Conclusion of Paper
Detection of CTCs in peripheral blood using the microfluidic chip system was more sensitive than the CellSearch System for the diagnosis of NSCLC with greater specificity. While detection of CTCs and CSCs was not correlated with patient age, sex, pathological type (adenocarcinoma or squamous cell carcinoma), it was significantly correlated with clinical stage-III/IV, metastasis, and treatment response. The sensitivity and specificity of CSC and CTC detection with the microfluidic chip system for the diagnosis of lung cancer were higher than with a combination of serum tumor markers. CTC and CSC positivity rates were lower in post-treatment patients with stable disease and complete or partial treatment response compared to rates in patients with progressive disease (P<0.05, all).
Studies
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Study Purpose
This study compared the sensitivity and specificity of detecting CTCs in peripheral blood from NSCLC patients using a microfluidic chip device to the CellSearch System. Correlations between patient age, gender, tumor classification, clinical stage, presence of metastases, treatment status, and serological tumor markers and CTC and CSC positivity rates as determined by microfluidic chip were also examined. Peripheral blood was collected from 80 patients (49 males and 31 females; 41≤60 years old and 39>60 years old) with NSCLC (44 with adenocarcinoma and 36 with squamous cell carcinoma, 22 Stage-I/II and 58 Stage-III/IV, 24 with metastasis and 56 without metastasis), 30 healthy people (control group 1), and 30 patients (control group 2) with benign diseases in lung (benign nodules in chest radiographs but without other tumor-like diseases). Blood collection and processing details were not provided. CTCs and CSCs were detected within 24 hours of collection with a microfluidic chip system consisting of three parts: a deterministic lateral displacement (DLD) sorting system, a magnetic field negative sorting system, and an immune affinity sorting system. Briefly, white cells and tumor cells were enriched from blood specimens by the DLD chip, CD45+ cells were enriched with the magnetic separation chip, EpCAM+ and SOX2+/OCT4+ cells were captured by the immune affinity sorting chip, and then CTCs and CSCs were detected by fluorescent microscopy (details not provided). Sensitivity and specificity of the microfluidic chip system were determined by comparing CTC detection with the CellSearch System. Criteria for positivity was 1 or more CTCs/2 mL blood. Serum was separated from 5mL peripheral blood by at 3000 rpm/min for 10-minute and the concentration of tumor markers (VEGF-C, CEA, CA125, and NSE) were measured by ELISA. Follow-up testing of 40 patients, post-treatment (surgery, chemotherapy, or targeted therapy) was performed to determine correlations between CTC and CSC positivity and response to treatment (partial or complete response, stable disease, or progressive disease).
Summary of Findings:
Detection of CTCs in peripheral blood using the microfluidic chip system was more sensitive than the CellSearch System for the diagnosis of NSCLC (95.1% vs 92.1%) with greater specificity (data not provided). Detection of CTCs and CSCs was not significantly correlated with patient age, sex, pathological type (adenocarcinoma or squamous cell carcinoma) but was significantly correlated with clinical stage-III/IV and metastasis (P<0.01, all). The sensitivity and specificity of CSC (94.5% and 71.0%, respectively) and CTC detection (93.6% and 78.9%, respectively) with the microfluidic chip system for the diagnosis of lung cancer were higher than with A combination of the serum tumor markers VEGF-C, CEA, CA125, and NSE (89.1% and 86.3%). Further, CTC and CSC positivity rates were lower in post-treatment patients with stable disease and complete or partial treatment response compared to rates in patients with progressive disease (P<0.05, all).
Biospecimens
Preservative Types
- None (Fresh)
Diagnoses:
- Normal
- Neoplastic - Benign
- Neoplastic - Carcinoma
Platform:
Analyte Technology Platform Protein ELISA Cell count/volume Fluorescent microscopy Pre-analytical Factors:
Classification Pre-analytical Factor Value(s) Preaquisition Patient age ≤60 years old
>60 years old
Preaquisition Patient gender Female
Male
Biospecimen Aliquots and Components Cell capture method CellSearch System
Microfluidic chip device
Biospecimen Acquisition Time of biospecimen collection Pre-treatment
Post-treatment
Preaquisition Diagnosis/ patient condition NSCLC with metastasis
NSCLC without metastasis
Adenocarcinoma
Squamous cell carcinoma
Preaquisition Prognostic factor Stage-I/II
Stage-III/IV