Prognostic significance of circulating tumor cells and tumor related transcripts in small cell lung cancer: A step further to clinical implementation

Small-cell lung cancer (SCLC) is a fatal disease with limited treatment options. Circulating tumor cells (CTCs) in liquid biopsy samples may serve as predictive and prognostic biomarkers; but the analysis of CTCs is still challenging. By using microfluidic or density gradient CTC enrichment in combination with immunofluorescent (IF) staining or qPCR of CTC-related transcripts, we achieved a 60.8% to 88.0% positivity in SCLC blood samples. Epithelial and neuroendocrine transcripts including the druggable target DLL3 were associated with shorter overall survival (OS), indicating the clinical value of these markers in terms of differential diagnosis and treatment decisions. High CTC counts and the presence of CTC duplets detected by IF staining were prognostic for OS, and thus may serve as indicators of disease progression or therapy failure. In patient samples with high CTC load detected by IF staining, a concordance of the transcripts positivity in circulating free plasma RNA and CTCs was observed. Our data emphasize the role of CTCs and CTC-related transcripts and underline the clinical value of liquid biopsy analysis in SCLC. Circulating tumor cells (CTCs) are detectable in most small cell lung cancers (SCLCs), often in relatively high numbers. But while CTCs are promising prognostic biomarkers in SCLC, further study is needed to optimize methods for their detection. Here, the authors investigated the utility of liquid biopsy analysis of CTCs for SCLC using a combination of approaches for CTC enrichment and immunofluorescent staining or qPCR of CTC-related transcripts. Pre-amplification for CTC-related transcript detection using qPCR maximized the number of positive findings in SCLC. Detection of cancer-related gene transcripts and high CTC counts were linked to shorter overall survival among SCLC patients. image