Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2021 Mar 22;11(1):6540.
doi: 10.1038/s41598-021-86122-4.

Development and validation for prognostic nomogram of epithelial ovarian cancer recurrence based on circulating tumor cells and epithelial-mesenchymal transition

Jiani Yang #  1 , Jun Ma #  1 , Yue Jin  1 , Shanshan Cheng  1 , Shan Huang  1 , Nan Zhang  1 , Yu Wang  2
Affiliations
Clinical Trial

Development and validation for prognostic nomogram of epithelial ovarian cancer recurrence based on circulating tumor cells and epithelial-mesenchymal transition

Jiani Yang et al. Sci Rep. .

Abstract

We aimed to determine the prognosis value of circulating tumor cells (CTCs) undergoing epithelial-mesenchymal transition in epithelial ovarian cancer (EOC) recurrence. We used CanPatrol CTC-enrichment technique to detect CTCs from blood samples and classify subpopulations into epithelial, mesenchymal, and hybrids. To construct nomogram, prognostic factors were selected by Cox regression analysis. Risk stratification was performed through Kaplan-Meier analysis among the training group (n = 114) and validation group (n = 38). By regression screening, both CTC counts (HR 1.187; 95% CI 1.098-1.752; p = 0.012) and M-CTC (HR 1.098; 95% CI 1.047-1.320; p = 0.009) were demonstrated as independent factors for recurrence. Other variables including pathological grade, FIGO stage, lymph node metastasis, ascites, and CA-125 were also selected (p < 0.005) to construct nomogram. The C-index of internal and external validation for nomogram was 0.913 and 0.874. We found significant predictive values for the nomogram with/without CTCs (AUC 0.8705 and 0.8097). Taking CTC counts and M-CTC into separation, the values were 0.8075 and 0.8262. Finally, survival curves of risk stratification based on CTC counts (p = 0.0241), M-CTC (p = 0.0107), and the nomogram (p = 0.0021) were drawn with significant differences. In conclusion, CTCs could serve as a novel factor for EOC prognosis. Nomogram model constructed by CTCs and other clinical parameters could predict EOC recurrence and perform risk stratification for clinical decision-making.Trial registration Chinese Clinical Trial Registry, ChiCTR-DDD-16009601, October 25, 2016.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
(A) Total CTC counts (top) and percentage of each CTC category (bottom) before treatment in ovarian cancer patients with or without recurrence. (B) The CTC image and (C) Magnetic Resonance Imaging (MRI) image of a representative patient who had the CTC-positive blood sample before treatment. (D) After tumor resection, the patient suffered cancer recurrence with (E) detectable liver metastasis observed by Magnetic Resonance Imaging (MRI) at 6-month follow-up.
Figure 2
Figure 2
The nomogram models 1-year recurrence rate and 2-year recurrence rate of ovarian cancer patients (A) based on CTC counts and M-CTC percentage; (B) without CTC counts and M-CTC percentage. The nomogram plots were generated by the “rms” package of R software.
Figure 3
Figure 3
The calibration curves of internal (A, B) and external (C, D) validation of the nomogram constructed in the training group based on CTCs count and M-CTC percentage. The predicted probabilities of 1-year and 2-year recurrence were consistent with the actual recurrence proportions of ovarian cancer patients. The calibration plots were generated by the “rms” package of R software.
Figure 4
Figure 4
The receive operating characteristic (ROC) curve of patients stratified by (A) CTC counts, M-CTC percentage, and CA-125; (B) nomogram-based risk groups The Kaplan–Meier curves for DFS of all the patients involved stratified by (C) M-CTC percentage; (D) CTC counts and risk groups of the nomogram (E) without or (F) with CTC counts and M-CTC percentage.
Figure 5
Figure 5
EOC Patient enrollment flow chart.
Figure 6
Figure 6
(A) Process of circulating tumor cells (CTCs) isolation and detection by CanPatrol CTC enrichment and ISH. (B–F) 5 representative images of patients with different CTC subpopulations, based on the RNA-ISH of mesenchymal (vimentin and Twist, green fluorescence) and epithelial (EpCAM and CK8/18/19, red fluorescence) markers.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J. Clin. 2020;70:7–30. doi: 10.3322/caac.21590. - DOI - PubMed
    1. Bray F, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2018;68:394–424. doi: 10.3322/caac.21492. - DOI - PubMed
    1. Jacobs IJ, et al. Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial. Lancet. 2016;387:945–956. doi: 10.1016/S0140-6736(15)01224-6. - DOI - PMC - PubMed
    1. Lowes LE, Allan AL. Circulating tumor cells and implications of the epithelial-to-mesenchymal transition. Adv. Clin. Chem. 2018;83:121–181. doi: 10.1016/bs.acc.2017.10.004. - DOI - PubMed
    1. Riethdorf S, et al. Detection of circulating tumor cells in peripheral blood of patients with metastatic breast cancer: a validation study of the Cell Search system. Clin. Cancer Res. 2007;13:920–928. doi: 10.1158/1078-0432.CCR-06-1695. - DOI - PubMed

Publication types

MeSH terms