Progress and application of circulating tumor cells in non-small cell lung cancer

Abstract

Non-small cell lung cancer (NSCLC) has the highest morbidity and mortality worldwide among malignant tumors. NSCLC is a great threat to health and well-being. Biopsy is the gold standard to diagnose lung cancer, but traditional biopsy methods cannot fully reflect the true condition of tumors. There is growing evidence that a single-point biopsy fails to reveal the complete landscape of the tumor due to intratumor heterogeneity, but it is impractical to complete multiple biopsies that are separated both spatially and temporally. Liquid biopsy heralds that a new era is coming. Circulating tumor cells (CTCs) are tumor cells that circulate in the peripheral blood after being shed from primary or metastatic tumors. CTCs constitute a considerable portion of a liquid biopsy, which contributes to the diagnosis, assessment of prognosis, and therapy of NSCLC. Herein, this review discusses the technologies for detection and enrichment of CTCs as well as clinical applications involving CTCs.

Keywords: CTCs; NSCLC; PD-L1; biomarker; circulating tumor cells; diagnosis; liquid biopsy; non-small cell lung cancer; prognosis; therapy.

Graphical abstract

Figure 1

Generation and metastasis of CTCs and CTC clusters CTCs are divided into single tumor cells and cell clusters. CTCs originate from the primary tumor or metastasis and can spread to nearby tissues or distant organs, such as liver, brain, and bones, with peripheral blood circulation.

Figure 2

Technologies for detection and enrichment of CTCs Cell enrichment involves capturing CTCs based on physical properties and biological properties. Physical properties include size, density, and electric charges, whereas biological properties involve surface protein expression and viability. Biological characteristics use either positive selection for targeting tumor-associated biomarkers or negative selection for removal of blood cells with common leukocyte biomarkers. Microfluidic platforms integrate physical and biological characteristics.

Figure 3

Clinical application of CTCs CTCs are useful in the diagnosis, prognosis, and treatment of NSCLC. CTC levels are significantly higher in patients with NSCLC than those with benign lung disease or healthy controls. Tumor types can be clarified according to different molecular markers on CTCs. The CTC counts are negatively related to overall survival (OS) and progression-free survival (PFS). Different molecular phenotypes also predict different prognoses. EMT(+)/GALC(+)/PD-L1(+)/OCT4(+) were significantly related to adverse outcomes. The current treatment of tumors, including lung cancer, involves a combination of surgical treatment, chemotherapy, targeted therapy, immunotherapy, and radiation therapy.