Skip to main content
Log in

Circulating tumor cells: a valuable indicator for locally advanced nasopharyngeal carcinoma

  • Head and Neck
  • Published:
European Archives of Oto-Rhino-Laryngology Aims and scope Submit manuscript

Abstract

Background

Advancements in nasopharyngeal carcinoma (NPC) treatment have led to a focus on personalized treatment. Circulating tumor cells (CTCs) are important for liquid biopsies and personalized treatment but are not being fully utilized. This study examined how pre- and post-treatment CTC counts, EMT subtypes, clinical characteristics, and patient prognosis are related in order to support the use of liquid biopsy in managing NPC.

Methods

This retrospective study included 141 patients with locally advanced NPC. All patients underwent CanPatrol™ CTC detection pre- and post-treatment and were categorized into EMT subtypes: epithelial type, mixed type, and mesenchymal type. This study analyzed CTC enumeration, EMT subtypes, and their associations with clinical characteristics and survival outcomes.

Results

The results indicated a positive correlation between the pre-treatment detection rate of CTCs and N stage (P < 0.01), alongside a positive correlation with the TNM clinical stage (P = 0.02). Additionally, the detection rate of mesenchymal CTCs post-treatment is positively associated with the N stage (P = 0.02). The enumeration of CTCs pre- and post-treatment is negatively correlated with prognosis and has statistical significance. Additionally, an investigation into the EMT subtypes of CTCs revealed a significant association between the presence of mesenchymal CTCs pre- and post-treatment and decreased overall survival (OS) (P < 0.05). Furthermore, T stage, N stage, TNM clinical stage, and Epstein-Barr virus (EBV) DNA were also significantly correlated with OS.

Conclusion

The study found that mesenchymal CTCs pre- and post-treatment, as well as the number of CTCs, were linked to a poor prognosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data availability

Data for this study are available from the corresponding author upon reasonable request.

References

  1. Chen Y-P, Chan ATC, Le Q-T, Blanchard P, Sun Y, Ma J (2019) Nasopharyngeal carcinoma. The Lancet 394:64–80. https://doi.org/10.1016/s0140-6736(19)30956-0

    Article  Google Scholar 

  2. Chang ET, Ye W, Zeng Y-X, Adami H-O (2021) The evolving epidemiology of nasopharyngeal carcinoma. Cancer Epidemiol Biomark Prev 30:1035–1047. https://doi.org/10.1158/1055-9965.Epi-20-1702

    Article  CAS  Google Scholar 

  3. He T, Yan R-N, Chen H-Y, Zeng Y-Y, Xiang Z-Z, Liu F et al (2021) Comparing the 7th and 8th editions of UICC/AJCC staging system for nasopharyngeal carcinoma in the IMRT era. BMC Cancer. https://doi.org/10.1186/s12885-021-08036-8

    Article  PubMed  PubMed Central  Google Scholar 

  4. Xia W-X, Zhang H-B, Shi J-L, Lu X, Wang L, Ye Y-F et al (2013) A prognostic model predicts the risk of distant metastasis and death for patients with nasopharyngeal carcinoma based on pre-treatment serum C-reactive protein and N-classification. Eur J Cancer 49:2152–2160. https://doi.org/10.1016/j.ejca.2013.03.003

    Article  CAS  PubMed  Google Scholar 

  5. Pan JJ, Ng WT, Zong JF, Lee SWM, Choi HCW, Chan LLK et al (2016) Prognostic nomogram for refining the prognostication of the proposed 8th edition of the AJCC/UICC staging system for nasopharyngeal cancer in the era of intensity-modulated radiotherapy. Cancer 122:3307–3315. https://doi.org/10.1002/cncr.30198

    Article  CAS  PubMed  Google Scholar 

  6. Bossi P, Chan AT, Licitra L, Trama A, Orlandi E, Hui EP et al (2021) Nasopharyngeal carcinoma: ESMO-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up†. Ann Oncol 32:452–465. https://doi.org/10.1016/j.annonc.2020.12.007

    Article  CAS  PubMed  Google Scholar 

  7. Tang LL, Chen YP, Chen CB, Chen MY, Chen NY, Chen XZ et al (2021) The Chinese Society of Clinical Oncology (CSCO) clinical guidelines for the diagnosis and treatment of nasopharyngeal carcinoma. Cancer Commun 41:1195–1227. https://doi.org/10.1002/cac2.12218

    Article  Google Scholar 

  8. Chen Y-P, Liu X, Zhou Q, Yang K-Y, Jin F, Zhu X-D et al (2021) Metronomic capecitabine as adjuvant therapy in locoregionally advanced nasopharyngeal carcinoma: a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial. The Lancet 398:303–313. https://doi.org/10.1016/s0140-6736(21)01123-5

    Article  CAS  Google Scholar 

  9. Zhang Y, Chen L, Hu G-Q, Zhang N, Zhu X-D, Yang K-Y et al (2019) Gemcitabine and cisplatin induction chemotherapy in nasopharyngeal carcinoma. N Engl J Med 381:1124–1135. https://doi.org/10.1056/NEJMoa1905287

    Article  CAS  PubMed  Google Scholar 

  10. Sun Y, Li W-F, Chen N-Y, Zhang N, Hu G-Q, Xie F-Y et al (2016) Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled trial. Lancet Oncol 17:1509–1520. https://doi.org/10.1016/s1470-2045(16)30410-7

    Article  CAS  PubMed  Google Scholar 

  11. Nikanjam M, Kato S, Kurzrock R (2022) Liquid biopsy: current technology and clinical applications. J Hematol Oncol. https://doi.org/10.1186/s13045-022-01351-y

    Article  PubMed  PubMed Central  Google Scholar 

  12. Alix-Panabières C, Pantel K (2021) Liquid biopsy: from discovery to clinical application. Cancer Discov 11:858–873. https://doi.org/10.1158/2159-8290.Cd-20-1311

    Article  PubMed  Google Scholar 

  13. Vasseur A, Kiavue N, Bidard FC, Pierga JY, Cabel L (2020) Clinical utility of circulating tumor cells: an update. Mol Oncol 15:1647–1666. https://doi.org/10.1002/1878-0261.12869

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Galvis MM, Romero CS, Bueno TO, and Teng Y (2021) Toward a new era for the management of circulating tumor cells, reviews on new drug targets in age-related disorders. pp 125–134

  15. Lowes LE and Allan AL (2018) Circulating tumor cells and implications of the epithelial-to-mesenchymal transition. pp 121–181

  16. Friendlander AH, Ettinger RL (2009) Karnofsky performance status scale. Spec Care Dentist 29:147–148. https://doi.org/10.1111/j.1754-4505.2009.00088.x

    Article  PubMed  Google Scholar 

  17. Wu J, Zhu H, Gao F, Wang R, Hu K (2021) Circulating Tumor Cells: a promising biomarker in the management of nasopharyngeal carcinoma. Front Oncol. https://doi.org/10.3389/fonc.2021.724150

    Article  PubMed  PubMed Central  Google Scholar 

  18. He Q, Zhou Y, Zhou J, Zhao D, Li L, Li X et al (2023) Clinical relevance of plasma EBV DNA as a biomarker for nasopharyngeal carcinoma in non-endemic areas: a multicenter study in southwestern China. Clin Chim Acta. https://doi.org/10.1016/j.cca.2023.117244

    Article  PubMed  Google Scholar 

  19. Siak PY, Khoo AS-B, Leong CO, Hoh B-P, Cheah S-C (2021) Current status and future perspectives about molecular biomarkers of nasopharyngeal carcinoma. Cancers. https://doi.org/10.3390/cancers13143490

    Article  PubMed  PubMed Central  Google Scholar 

  20. Tan R, Phua SKA, Soong YL, Oon LLE, Chan KS, Lucky SS et al (2020) Clinical utility of Epstein-Barr virus DNA and other liquid biopsy markers in nasopharyngeal carcinoma. Cancer Commun 40:564–585. https://doi.org/10.1002/cac2.12100

    Article  Google Scholar 

  21. Yang W-Y, Feng L-F, Meng X, Chen R, Xu W-H, Hou J et al (2020) Liquid biopsy in head and neck squamous cell carcinoma: circulating tumor cells, circulating tumor DNA, and exosomes. Expert Rev Mol Diagn 20:1213–1227. https://doi.org/10.1080/14737159.2020.1855977

    Article  CAS  PubMed  Google Scholar 

  22. Wen Z, Li Z, Yong P, Liang D, Xie D, Chen H et al (2019) Detection and clinical significance of circulating tumor cells in patients with nasopharyngeal carcinoma. Oncol Lett. https://doi.org/10.3892/ol.2019.10560

    Article  PubMed  PubMed Central  Google Scholar 

  23. Xie X-Q, Luo Y, Ma XL, Li S-S, Liu L, Zhang H, Li P, Wang F (2019) Clinical significance of circulating tumor cells and their expression of cyclooxygenase-2 in patients with nasopharyngeal carcinoma. Eur Rev Med Pharmacol Sci. https://doi.org/10.26355/eurrev_201908_18735

    Article  PubMed  Google Scholar 

  24. Dongre A, Weinberg RA (2018) New insights into the mechanisms of epithelial–mesenchymal transition and implications for cancer. Nat Rev Mol Cell Biol 20:69–84. https://doi.org/10.1038/s41580-018-0080-4

    Article  CAS  Google Scholar 

  25. Huang RY-J, Guilford P, Thiery JP (2012) Early events in cell adhesion and polarity during epithelial-mesenchymal transition. J Cell Sci 125:4417–4422. https://doi.org/10.1242/jcs.099697

    Article  CAS  PubMed  Google Scholar 

  26. Brabletz T, Jung A, Reu S, Porzner M, Hlubek F, Kunz-Schughart LA et al (2001) Variable beta-catenin expression in colorectal cancers indicates tumor progression driven by the tumor environment. Proc Natl Acad Sci U S A 98(18):10356–10361. https://doi.org/10.1073/pnas.171610498

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Beerling E, Seinstra D, de Wit E, Kester L, van der Velden D, Maynard C et al (2016) Plasticity between epithelial and mesenchymal states unlinks EMT from metastasis-enhancing stem cell capacity. Cell Rep 14:2281–2288. https://doi.org/10.1016/j.celrep.2016.02.034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Ou G, Xing S, Li J, Zhang L, Chen S (2019) Circulating tumor cells: a valuable marker of poor prognosis for advanced nasopharyngeal carcinoma. Mol Med. https://doi.org/10.1186/s10020-019-0112-3

    Article  PubMed  PubMed Central  Google Scholar 

  29. Qian Y, Wu Y, Yuan Z, Niu X, He Y, Peng J et al (2019) The frequency of circulating tumour cells and the correlation with the clinical response to standard chemoradiotherapy in locally advanced nasopharyngeal carcinoma: a prospective study. Cancer Manage Res 11:10187–10193. https://doi.org/10.2147/cmar.S222916

    Article  CAS  Google Scholar 

  30. Gao T, Mao J, Huang J, Luo F, Lin L, Lian Y et al (2023) Prognostic significance of circulating tumor cell measurement in the peripheral blood of patients with nasopharyngeal carcinoma. Clinics. https://doi.org/10.1016/j.clinsp.2023.100179

    Article  PubMed  PubMed Central  Google Scholar 

  31. Shibue T, Weinberg RA (2017) EMT, CSCs, and drug resistance: the mechanistic link and clinical implications. Nat Rev Clin Oncol 14:611–629. https://doi.org/10.1038/nrclinonc.2017.44

    Article  PubMed  PubMed Central  Google Scholar 

  32. Byers LA, Diao L, Wang J, Saintigny P, Girard L, Peyton M et al (2013) An epithelial-mesenchymal transition gene signature predicts resistance to EGFR and PI3K inhibitors and identifies Axl as a therapeutic target for overcoming EGFR inhibitor resistance. Clin Cancer Res 19:279–290. https://doi.org/10.1158/1078-0432.Ccr-12-1558

    Article  CAS  PubMed  Google Scholar 

  33. Mittal V (2018) Epithelial mesenchymal transition in tumor metastasis. Annu Rev Pathol 13:395–412. https://doi.org/10.1146/annurev-pathol-020117-043854

    Article  CAS  PubMed  Google Scholar 

  34. Tsao SW, Tsang CM, Lo KW (2017) Epstein-Barr virus infection and nasopharyngeal carcinoma. Philos Trans R Soc B. https://doi.org/10.1098/rstb.2016.0270

    Article  Google Scholar 

  35. Lee AWM, Lee VHF, Ng W-T, Strojan P, Saba NF, Rinaldo A et al (2021) A systematic review and recommendations on the use of plasma EBV DNA for nasopharyngeal carcinoma. Eur J Cancer 153:109–122. https://doi.org/10.1016/j.ejca.2021.05.022

    Article  CAS  PubMed  Google Scholar 

  36. Trevisiol C, Gion M, Vaona A, Fabricio ASC, Roca E, Licitra L et al (2021) The appropriate use of circulating EBV-DNA in nasopharyngeal carcinoma: comprehensive clinical practice guidelines evaluation. Oral Oncol. https://doi.org/10.1016/j.oraloncology.2020.105128

    Article  PubMed  Google Scholar 

  37. Hsu C-L, Chan S-C, Chang K-P, Lin T-L, Lin C-Y, Hsieh C-H et al (2013) Clinical scenario of EBV DNA follow-up in patients of treated localized nasopharyngeal carcinoma. Oral Oncol 49:620–625. https://doi.org/10.1016/j.oraloncology.2013.02.006

    Article  PubMed  Google Scholar 

  38. Yap K, Cohen EN, Reuben JM, Khoury JD (2019) Circulating Tumor Cells: state-of-the-art update on technologies and clinical applications. Curr Hematol Malig Rep 14:353–357. https://doi.org/10.1007/s11899-019-00531-x

    Article  PubMed  Google Scholar 

  39. Yu Y, Lin Z-X, Li H-W, Luo H-Q, Yang D-H, Zhou H-C et al (2020) Circulating tumor cells and fibronectin 1 in the prognosis of nasopharyngeal carcinoma. Technol Cancer Res Treat. https://doi.org/10.1177/1533033820909911

    Article  PubMed  PubMed Central  Google Scholar 

  40. Li Y-J, Luo Y, Xie X-Q, Li P, Wang F (2018) The prognostic value of COX-2 expression on circulating tumor cells in nasopharyngeal carcinoma: a prospective analysis. Radiother Oncol 129:396–402. https://doi.org/10.1016/j.radonc.2018.07.022

    Article  CAS  PubMed  Google Scholar 

  41. Liu Z, Li L, Yang Z, Luo W, Li X, Yang H et al (2010) Increased expression of MMP9 is correlated with poor prognosis of nasopharyngeal carcinoma. BMC Cancer. https://doi.org/10.1186/1471-2407-10-270

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors would like to thank all the patients, investigators, and institutions involved in this study.

Funding

This work was supported by grants from the National Natural Science Foundation of China (No. 71964003, 81460460, 81760542, 82260467), The Natural Science Foundation of Guangxi Zhuang Autonomous Region (No. 2018JJA141048).

Author information

Authors and Affiliations

Authors

Contributions

Conceptualization: Ting Liu, Chunmei Chen, Lihe He, Jing Liu; Methodology: Ting Liu, Guimei Wang; Formal analysis and investigation: Ting Liu, Guimei Wang; Writing—original draft preparation: Ting Liu, Chunmei Chen, Lihe He, Jing Liu; Writing—review and editing: Ting Liu, Chunmei Chen; Funding acquisition: Rensheng Wang; Resources: Rensheng Wang; Supervision: Ting Liu, Rensheng Wang, Chunli Ouyang.

Corresponding authors

Correspondence to Rensheng Wang or Chunli Ouyang.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Institutional review board statement

The study was conducted in accordance with the Declaration of Helsinki, and approved by the Ethics Committee of the First Affiliated Hospital of Guangxi Medical University (2024-E178-01, March 13, 2024).

Informed consent

All participants in the study received informed consent.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, T., Liu, J., Wang, G. et al. Circulating tumor cells: a valuable indicator for locally advanced nasopharyngeal carcinoma. Eur Arch Otorhinolaryngol (2024). https://doi.org/10.1007/s00405-024-08714-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00405-024-08714-w

Keywords

Navigation