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

Int J Cancer. 2024 Jun 15;154(12):2189-2199. doi: 10.1002/ijc.34886. Epub 2024 Feb 14.

Abstract

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.

Keywords: circulating free RNA; circulating tumor cells; gene expression analysis; microfluidics; prognostic marker.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Lung Neoplasms* / pathology
  • Membrane Proteins
  • Neoplastic Cells, Circulating* / pathology
  • Prognosis
  • Small Cell Lung Carcinoma* / drug therapy

Substances

  • Biomarkers, Tumor
  • DLL3 protein, human
  • Membrane Proteins
  • Intracellular Signaling Peptides and Proteins