Scientific Reports (Mar 2023)

Genomic characteristics and clinical significance of CD56+ circulating tumor cells in small cell lung cancer

  • Charles Ricordel,
  • L. Chaillot,
  • E. I. Vlachavas,
  • M. Logotheti,
  • A. Jouannic,
  • T. Desvallees,
  • G. Lecuyer,
  • M. Aubry,
  • G. Kontogianni,
  • C. Mastrokalou,
  • F. Jouan,
  • U. Jarry,
  • R. Corre,
  • Y. Le Guen,
  • T. Guillaudeux,
  • H. Lena,
  • A. Chatziioannou,
  • Rémy Pedeux

DOI
https://doi.org/10.1038/s41598-023-30536-9
Journal volume & issue
Vol. 13, no. 1
pp. 1 – 11

Abstract

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Abstract Circulating tumor cells (CTC) have been studied in various solid tumors but clinical utility of CTC in small cell lung cancer (SCLC) remains unclear. The aim of the CTC-CPC study was to develop an EpCAM-independent CTC isolation method allowing isolation of a broader range of living CTC from SCLC and decipher their genomic and biological characteristics. CTC-CPC is a monocentric prospective non-interventional study including treatment-naïve newly diagnosed SCLC. CD56+ CTC were isolated from whole blood samples, at diagnosis and relapse after first-line treatment and submitted to whole-exome-sequencing (WES). Phenotypic study confirms tumor lineage and tumorigenic properties of isolated cells for the 4 patients analyzed with WES. WES of CD56+ CTC and matched tumor biopsy reveal genomic alteration frequently impaired in SCLC. At diagnosis CD56+ CTC were characterized by a high mutation load, a distinct mutational profile and a unique genomic signature, compared to match tumors biopsies. In addition to classical pathways altered in SCLC, we found new biological processes specifically affected in CD56+ CTC at diagnosis. High numeration of CD56+ CTC (> 7/ml) at diagnosis was associated with ES-SCLC. Comparing CD56+ CTC isolated at diagnosis and relapse, we identify differentially altered oncogenic pathways (e.g. DLL3 or MAPK pathway). We report a versatile method of CD56+ CTC detection in SCLC. Numeration of CD56+ CTC at diagnosis is correlated with disease extension. Isolated CD56+ CTC are tumorigenic and show a distinct mutational profile. We report a minimal gene set as a unique signature of CD56+ CTC and identify new affected biological pathways enriched in EpCAM-independent isolated CTC in SCLC.