Abstract: Objective:To evaluate the practicability and feasibility of detection of circulating tumor cells (CTC) combined with exosome miR-21 in the diagnosis of ground glass opacity(GGO), and to provide the evidence for the diagnosis of GGO. Methods:Seventy patients were selected according to the diagnostic and exclusion criteria of GGO. All the patients underwent thoracoscopic segmentectomy. The patients diagnosed as lung cancer after operation were regarded as case group (n=24), and the patients diagnosed as benign lesion after operation were regarded as control group (n=46). Before operation, CTC was captured from the peripheral blood by negative enrichment of immunomagnetic beads. CTC was labeled with tumor-specific folate ligand-oligonucleotide conjugate. The exosomes of the same specimen were detected, purified and identified, and the expression levels of serum exosome miR-21 of the patients in two groups were detected. The diagnostic efficacies of CTC and exosome miR-21 in the GGO paitents were evaluated by ROC curves. Results:The positive rate of CTC in the patients in case group was higher than that in control group (P<0.05). There were no significant differences in the positive rates of CTC between the patients with different pathological types in case group and control group (P>0.05). The purified samples showed exosome characteristics. The expression level of serum exosome miR-21 in the patients in case group was higher than that in control group (P<0.05). The area under ROC curve (AUC) of CTC was 0.891, and the AUC of exosome miR-21 was 0.711, which showed good specificity. The sensitivity and specificity of the combined detection were 85.64% and 86.79%,respectively. Conclusion:The detection of CTC combined with exosome miR-21 can be used in the clinical diagnosis of early lung cancer with high sensitivity and specificity.

Key words: folate receptor, circulating tumor cell, exosome, ground glass opacity, miR-21