Dynamic detection of HER2 of circulating tumor cells in patients with gastric carcinoma and its clinical application

Mol Med Rep. 2022 May;25(5):187. doi: 10.3892/mmr.2022.12703. Epub 2022 Mar 29.

Abstract

The aim of the present study was to construct and characterize human epidermal growth factor receptor 2 (HER2) lipid magnetic ball (H‑LMB) for separating circulating tumor cells (CTCs) in patients with gastric carcinoma (GC) and to compare the result of separated CTC counts with that of next‑generation sequencing (NGS) for single‑gene analysis to verify the consistency for evaluating the association between the detection results and the progress of clinical treatment, so as to facilitate early diagnosis and dynamic monitoring of GC. A lipid magnetic ball (LMB), coated with Fe3O4 nanoparticles, was synthesized by microemulsion technique and an anti‑HER2 antibody was conjugated to the surface of LMB to form H‑LMB, followed by the characterization of the prepared H‑LMB. The detection of capture efficiency of LMBs in GC cells was tested by MTT and expression of HER2 mRNA was determined by reverse transcription‑quantitative PCR. The positive detection rate of HER2 was verified by HER2‑fluorescence in situ hybridization (FISH) test on the separated CTCs from GC. Further verification was performed based on the consistency between the result of separated CTCs and that of single‑gene NGS assay of HER2, associated with the determination of clinical consistency. The constructed H‑LMB exhibited good stability and specificity. The mutation rate of HER2 by the FISH test was 14% in the blood samples of 50 patients with GC and was 14% by NGS assay. The mutation rate of HER2 was 12% in H‑LMB and the positive detection rate was 85.7% compared with the results of the FISH test, indicating consistency with the clinical diagnosis and pathological examination results. In conclusion, the anti‑HER2 antibody‑modified LMB can separate CTCs with HER2 abnormal expression, which exhibits an application potential in GC diagnosis and treatment and is of great clinical significance for the diagnosis and evaluation of its therapeutic effect on GC.

Keywords: circulating tumor cell; gastric carcinoma; human epidermal growth factor receptor 2; lipid magnetic ball; next‑generation sequencing.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Breast Neoplasms*
  • Carcinoma*
  • Female
  • Humans
  • In Situ Hybridization, Fluorescence
  • Neoplastic Cells, Circulating* / metabolism
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism

Substances

  • Biomarkers, Tumor
  • ERBB2 protein, human
  • Receptor, ErbB-2