Detection and clinical significance of circulating tumor cells in patients with nasopharyngeal carcinoma

Wen,Zunbei; Li,Zhongtai; Yong,Pangxiao; Liang,Dunbo; Xie,Di; Chen,Haiwen; Yang,Yongying; Wu,Shiyang; Li,Cong; Cheng,Zhen

doi:10.3892/ol.2019.10560

Detection and clinical significance of circulating tumor cells in patients with nasopharyngeal carcinoma

Authors:
- Zunbei Wen
- Zhongtai Li
- Pangxiao Yong
- Dunbo Liang
- Di Xie
- Haiwen Chen
- Yongying Yang
- Shiyang Wu
- Cong Li
- Zhen Cheng
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Affiliations: Department of Radiotherapy, The People's Hospital of Gaozhou, Gaozhou, Guangdong 525200, P.R. China, SurExam Bio‑Tech, Guangzhou Technology Innovation Base, Guangzhou, Guangdong 510000, P.R. China
Published online on: July 4, 2019 https://doi.org/10.3892/ol.2019.10560
Pages: 2537-2547

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Abstract

Nasopharyngeal carcinoma (NPC) is the most common cancer type originating in the nasopharynx, and varies notably from other cancer types of the head and neck in its occurrence, causes, clinical behavior and treatment. Significant effort has been made into understanding the biological properties of circulating tumor cells (CTCs), with previous studies demonstrating the critical role CTCs serve in the metastatic spread of carcinoma. However, associations between NPC and CTCs have not been completely elucidated. Therefore, in the present study, the CanPatrol™ CTC‑enrichment technique and classical in situ hybridization assay were utilized to acquire, identify and classify CTCs from patients with NPC. Subsequently, the correlation between CTCs and the clinical indexes, progression‑free survival (PFS), N‑cadherin gene expression and the response to therapy were investigated. The present study then determined whether the Wnt/β‑catenin signaling pathway served a role in therapy for NPC cells. Collectively, the research demonstrated that CTCs could be detected in patients with NPC. Additionally, CTCs exhibited a statistically significant association with the Epstein‑Barr virus infection prior to therapy and Eastern Cooperative Oncology Group score following therapy. Furthermore, co‑treatment with cisplatin and paclitaxel significantly decreased the number of CTCs. In addition, mesenchymal CTCs may serve as a predictor of PFS. Finally, the present study demonstrated that cisplatin combined with paclitaxel induced apoptosis and decreased the tumor markers in NPC cells through the Wnt/β‑catenin signaling pathway. In conclusion, these data indicated that CTCs may serve as a biomarker in monitoring the therapeutic efficacy of treatments for NPC. Furthermore, the Wnt/β‑catenin signaling pathway served a therapeutic role in the treatment of NPC.

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1	Cao SM, Simons MJ and Qian CN: The prevalence and prevention of nasopharyngeal carcinoma in China. Chin J Cancer. 30:114–119. 2011. View Article : Google Scholar : PubMed/NCBI
2	Horikawa T, Yoshizaki T, Kondo S, Furukawa M, Kaizaki Y and Pagano JS: Epstein-Barr Virus latent membrane protein 1 induces Snail and epithelial-mesenchymal transition in metastatic nasopharyngeal carcinoma. Br J Cancer. 104:1160–1167. 2011. View Article : Google Scholar : PubMed/NCBI
3	Chan AT: Nasopharyngeal carcinoma. Ann Oncol. 21 (Suppl 7):vii308–vii312. 2010. View Article : Google Scholar : PubMed/NCBI
4	Lin JH, Jiang CQ, Ho SY, Zhang WS, Mai ZM, Xu L, Lo CM and Lam TH: Smoking and nasopharyngeal carcinoma mortality: A cohort study of 101,823 adults in Guangzhou, China. BMC Cancer. 15:9062015. View Article : Google Scholar : PubMed/NCBI
5	Sousa H, Mesquita L, Ribeiro J, Catarino R, Breda E and Medeiros R: Polymorphisms in host immune response associated genes and risk of nasopharyngeal carcinoma development in Portugal. Immunobiology. 221:145–152. 2016. View Article : Google Scholar : PubMed/NCBI
6	Ashworth TR: A case of cancer in which cells similar to those in the tumours were seen in the blood after death. Aust Med J. 14:146–149. 1869.
7	Gupta GP and Massagué J: Cancer metastasis: building a framework. Cell. 127:679–695. 2006. View Article : Google Scholar : PubMed/NCBI
8	Książkiewicz M, Markiewicz A and Żaczek AJ: Epithelial-mesenchymal transition: A hallmark in metastasis formation linking circulating tumor cells and cancer stem cells. Pathobiology. 79:195–208. 2012. View Article : Google Scholar : PubMed/NCBI
9	Guarino M: Epithelial-mesenchymal transition and tumour invasion. Int J Biochem Cell Biol. 39:2153–2160. 2007. View Article : Google Scholar : PubMed/NCBI
10	Lecharpentier A, Vielh P, Perez-Moreno P, Planchard D, Soria JC and Farace F: Detection of circulating tumour cells with a hybrid (epithelial/mesenchymal) phenotype in patients with metastatic non-small cell lung cancer. Br J Cancer. 105:1338–1341. 2011. View Article : Google Scholar : PubMed/NCBI
11	Economopoulou P, Georgoulias V and Kotsakis A: Classifying circulating tumor cells to monitor cancer progression. Expert Rev Mol Diagn. 17:153–165. 2017. View Article : Google Scholar : PubMed/NCBI
12	Cai LL, Ye HM, Zheng LM, Ruan RS and Tzeng CM: Circulating tumor cells (CTCs) as a liquid biopsy material and drug target. Curr Drug Targets. 15:965–972. 2014.PubMed/NCBI
13	Cristofanilli M: Circulating tumor cells, disease progression, and survival in metastatic breast cancer. Semin Oncol 33 (3 Suppl 9). S9–S14. 2006.
14	Nolé F, Munzone E, Zorzino L, Minchella I, Salvatici M, Botteri E, Medici M, Verri E, Adamoli L, Rotmensz N, et al: Variation of circulating tumor cell levels during treatment of metastatic breast cancer: Prognostic and therapeutic implications. Ann Oncol. 19:891–897. 2008. View Article : Google Scholar : PubMed/NCBI
15	Cohen SJ, Punt CJ, Iannotti N, Saidman BH, Sabbath KD, Gabrail NY, Picus J, Morse M, Mitchell E, Miller MC, et al: Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. J Clin Oncol. 26:3213–3221. 2008. View Article : Google Scholar : PubMed/NCBI
16	Fina E, Necchi A, Giannatempo P, Colecchia M, Raggi D, Daidone MG and Cappelletti V: Clinical significance of early changes in circulating tumor cells from patients receiving first-line cisplatin-based chemotherapy for metastatic urothelial carcinoma. Bladder Cancer. 2:395–403. 2016. View Article : Google Scholar : PubMed/NCBI
17	Hirose T, Oki Y, Kusumoto S, Sugiyama T, Shirai T, Nakashima M, Yamaoka T, Okuda K, Ohnishi T, Ohmori T and Adachi M: Circulating tumor cells as a predictive marker for chemotherapy and prognostic marker in patients with metastatic non-small cell lung cancer. J Clin Oncol. 29 (Suppl 15):e210202011. View Article : Google Scholar
18	Hall C, Valad L and Lucci A: Circulating tumor cells in breast cancer patients. Crit Rev Oncog. 21:125–139. 2016. View Article : Google Scholar : PubMed/NCBI
19	Alva A, Friedlander T, Clark M, Huebner T, Daignault S, Hussain M, Lee C, Hafez K, Hollenbeck B, Weizer A, et al: Circulating tumor cells as potential biomarkers in bladder cancer. J Urol. 194:790–798. 2015. View Article : Google Scholar : PubMed/NCBI
20	Derycke LD and Bracke ME: N-cadherin in the spotlight of cell-cell adhesion, differentiation, embryogenesis, invasion and signalling. Int J Dev Bio. 48:463–476. 2004. View Article : Google Scholar
21	Craig SE and Brady-Kalnay SM: Cancer cells cut homophilic cell adhesion molecules and run. Cancer Res. 71:303–309. 2011. View Article : Google Scholar : PubMed/NCBI
22	Nieman MT, Prudoff RS, Johnson KR and Wheelock MJ: N-cadherin promotes motility in human breast cancer cells regardless of their E-cadherin expression. J Cell Biol. 147:631–644. 1999. View Article : Google Scholar : PubMed/NCBI
23	Araki K, Shimura T, Suzuki H, Tsutsumi S, Wada W, Yajima T, Kobayahi T, Kubo N and Kuwano H: E/N-cadherin switch mediates cancer progression via TGF-β-induced epithelial-to-mesenchymal transition in extrahepatic cholangiocarcinoma. Br J Cancer. 105:1885–1893. 2011. View Article : Google Scholar : PubMed/NCBI
24	Li S and Jiao J: Effects of N-cadherin expression on cell cycle, cell apoptosis and invasiveness and metastasis of tongue squamous cell carcinoma cell line Tca8113 cells. Zhonghua Kou Qiang Yi Xue Za Zhi. 46:365–369. 2011.(In Chinese). PubMed/NCBI
25	Hazan RB, Phillips GR, Qiao RF, Norton L and Aaronson SA: Exogenous expression of N-cadherin in breast cancer cells induces cell migration, invasion, and metastasis. J Cell Biol. 148:779–790. 2000. View Article : Google Scholar : PubMed/NCBI
26	Valkenburg KC, Graveel CR, Zylstra-Diegel CR, Zhong Z and Williams BO: Wnt/β-catenin signaling in normal and cancer stem cells. Cancers (Basel). 3:2050–2079. 2011. View Article : Google Scholar : PubMed/NCBI
27	Chen K, Huang Y and Chen J: Understanding and targeting cancer stem cells: Therapeutic implications and challenges. Acta Pharmacol Sin. 34:732–740. 2013. View Article : Google Scholar : PubMed/NCBI
28	Lin QQ, Jin-Tian LI and Wang M: Role of Wnt/β-catenin pathway in differentiation of nasopharyngeal carcinoma. J Sun Yat-sen Univ (Med Sci). 4:384–387. 2005.(In Chinese).
29	Wu S, Liu Z, Liu S, Lin L, Yang W and Xu J: Enrichment and enumeration of circulating tumor cells by efficient depletion of leukocyte fractions. Clin Chem Lab Med. 52:243–251. 2014. View Article : Google Scholar : PubMed/NCBI
30	Wu S, Liu S, Liu Z, Huang J, Pu X, Li J, Yang D, Deng H, Yang N and Xu J: Classification of circulating tumor cells by epithelial-mesenchymal transition markers. PLoS One. 10:e01239762015. View Article : Google Scholar : PubMed/NCBI
31	Tsongalis GJ: Branched DNA technology in molecular diagnostics. Am J Clin Pathol. 126:448–453. 2006. View Article : Google Scholar : PubMed/NCBI
32	Horn T, Chang CA and Urdea MS: Chemical synthesis and characterization of branched oligodeoxyribonucleotides (bDNA) for use as signal amplifiers in nucleic acid quantification assays. Nucleic Acids Res. 25:4842–4849. 1997. View Article : Google Scholar : PubMed/NCBI
33	Chan AT: Nasopharyngeal carcinoma. Ann Oncol. 21 (Suppl 7):vii308–vii312. 2010. View Article : Google Scholar : PubMed/NCBI
34	Wei KR, Xu Y, Liu J, Zhang WJ and Liang ZH: Histopathological classification of nasopharyngeal carcinoma. Asian Pac J Cancer Prev. 12:1141–1147. 2011.PubMed/NCBI
35	Hui EP, Ma BB, King AD, Mo F, Chan SL, Kam MK, Loong HH, Ahuja AT, Zee BC and Chan AT: Hemorrhagic complications in a phase ii study of sunitinib in patients of nasopharyngeal carcinoma who has previously received high-dose radiation. Ann Oncol. 22:1280–1287. 2011. View Article : Google Scholar : PubMed/NCBI
36	Luo WR, Wu AB, Fang WY, Li SY and Yao KT: Nuclear expression of N-cadherin correlates with poor prognosis of nasopharyngeal carcinoma. Histopathology. 61:237–246. 2012. View Article : Google Scholar : PubMed/NCBI
37	Shi L, Wu YX, Yu JH, Chen X, Luo XJ and Yin YR: Research of the relationship between β-catenin and c-myc-mediated Wnt pathway and laterally spreading tumors occurrence. Eur Rev Med Pharmacol Sci. 21:252–257. 2017.PubMed/NCBI
38	OuYang PY, Su Z, Ma XH, Mao YP, Liu MZ and Xie FY: Comparison of TNM staging systems for nasopharyngeal carcinoma, and proposal of a new staging system. Br J Cancer. 109:2987–2997. 2013. View Article : Google Scholar : PubMed/NCBI
39	Mehta S, Shelling A, Muthukaruppan A, Lasham A, Blenkiron C, Laking G and Print C: Predictive and prognostic molecular markers for cancer medicine. Ther Adv Med Oncol. 2:125–148. 2010. View Article : Google Scholar : PubMed/NCBI
40	Micalizzi DS, Haber DA and Maheswaran S: Cancer metastasis through the prism of epithelial-to-mesenchymal transition in circulating tumor cells. Mol Oncol. 11:770–780. 2017. View Article : Google Scholar : PubMed/NCBI
41	Alix-Panabieres C and Pantel K: The circulating tumor cells: Liquid biopsy of cancer. Klin Lab Diagn. 60–64. 2014.(In Russian). PubMed/NCBI
42	Si Y, Lan G, Deng Z, Wang Y, Lu Y, Qin Y, Huang B, Yang Y, Weng J, Han X, et al: Distribution and clinical significance of circulating tumor cells in nasopharyngeal carcinoma. Jpn J Clin Oncol. 46:622–630. 2016. View Article : Google Scholar : PubMed/NCBI
43	Chen X and Tang Q: The impact of radiotherapy course length on the treatment results of nasopharyngeal carcinoma (NPC). Chin J Cancer Res. 7:130–133. 1995. View Article : Google Scholar
44	Ren JH, Dai XF, Yan GL, Jin M, Liu CW, Yang KY, Wu G and Ma CM: Acute oral mucositis in nasopharyngeal carcinoma patients treated with radiotherapy: association with genetic polymorphism in DNA DSB repair genes. Int J Radiat Biol. 90:256–261. 2014. View Article : Google Scholar : PubMed/NCBI
45	Lengyel E, Baricza K, Somogyi A, Olajos J, Pápai Z, Godény M, Németh G and Esik O: Reirradiation of locally recurrent nasopharyngeal carcinoma. Strahlenther Onkol. 179:298–305. 2003. View Article : Google Scholar : PubMed/NCBI
46	Kong FF, Ying H, Du CR, Huang S, Zhou JJ and Hu CS: Effectiveness and toxicities of intensity-modulated radiation therapy for patients with T4 nasopharyngeal carcinoma. PLoS One. 9:e913622014. View Article : Google Scholar : PubMed/NCBI
47	Paterlini-Brechot P and Benali NL: Circulating tumor cells (CTC) detection: Clinical impact and future directions. Cancer Lett. 253:180–204. 2007. View Article : Google Scholar : PubMed/NCBI
48	Hatta K, Nose A, Nagafuchi A and Takeichi M: Cloning and expression of cDNA encoding a neural calcium-dependent cell adhesion molecule: Its identity in the cadherin gene family. J Cell Biol. 106:873–881. 1988. View Article : Google Scholar : PubMed/NCBI
49	Micalizzi DS, Farabaugh SM and Ford HL: Epithelial-mesenchymal transition in cancer: Parallels between normal development and tumor progression. J Mammary Gland Biol Neoplasia. 15:117–134. 2010. View Article : Google Scholar : PubMed/NCBI
50	Iwatsuki M, Mimori K, Yokobori T, Ishi H, Beppu T, Nakamori S, Baba H and Mori M: Epithelial-mesenchymal transition in cancer development and its clinical significance. Cancer Sci. 101:293–299. 2010. View Article : Google Scholar : PubMed/NCBI
51	Drocaş AI, Tomescu PI, Mitroi G, Drăgoescu PO, Mărgăritescu C, Stepan AE, Şurlin V, CrăiŢoiu Ş, Drocaş I, Ungureanu AM, et al: The cadherin switch assessment in the epithelial-mesenchymal transition of urothelial bladder carcinomas. Rom J Morphol Embryol. 57:1037–1044. 2016.PubMed/NCBI