Karyotyping of circulating tumor cells for predicting chemotherapeutic sensitivity and efficacy in patients with esophageal cancer

Abstract

Background: Aneuploidy of chromosome 8 in circulating tumor cells (CTCs) has been reported correlates with therapeutic efficacy and prognosis in patients with advanced gastric cancer. However, it is not clear whether it is also appropriate for other cancer. Therefore, in this study, we evaluate the clinical application aneuploidy of CTCs for esophageal cancer.

Methods: Peripheral blood were collected for karyotyping analysis before and after first 4-cycles chemotherapy from seventy nine patients with newly diagnosed esophageal cancer. Karyotyping of chromosome 8 in CTCs detected by SET-iFISH (Subtraction Enrichment-Immunostaining fluorescence in situ hybridizatio) in those patients were grouped into two categories according to CTC number: triploid group and non-triploid group. Pearson Chi-Square were used to compare the association between different aneuploidy type and chemotherapeutic sensitivity and efficacy.

Results: Among the 16 patients with triploid of chromosome 8, 4 patients benefit, and of the 63 patients with non-triploid, 54 patients benefit. Chi-square test analysis found that clinical benefit of non-triploid patients was significantly higher than triploid patients, suggesting non-triploid patients were more sensitive to chemotherapy than triploid patients. After 4-cycles chemotherapy, it is found that chemotherapeutic efficacy was positively correlated with non-triploid proportion. These results suggest that non-triploid proportion could be used as a candidate maker for assessing chemotherapeutic efficacy.

Conclusions: Monitoring aneuploidy of chromosome 8 in CTCs before and after chemotherapy may help predict sensitivity and efficacy of chemotherapy in patients with esophageal cancer.

Keywords: Chemotherapeutic efficacy; Circulating tumor cells (CTCs); Esophageal cancer; Triploid/non-triploid patient.

Fig. 1

Images of CTCs with different ploidies of chromosome 8. (a) triploidy, (b) tetraploidy, (c) pentaploidy, and (d) > 5 copies. Nuclei of CTCs were stained with 4′, 6-diamidino-2-phenylindole (blue) and the chromosome 8 was identified by centromere probe 8 Spectrum Orange probe (red dots). Scale bar = 5 μm

Fig. 2

The association between chemotherapeutic efficacy and non-triploid proportion. PR: Partial Response; PD: Progressive Disease; SD: Stable Disease. 1 in X axial represent PR; 2 in X axial represent SD; 3 in X axial represent PD.