Int J Stomatol ›› 2021, Vol. 48 ›› Issue (2): 205-212.doi: 10.7518/gjkq.2021028

• Reviews • Previous Articles     Next Articles

Research progress on the relationship between circulating tumor cells and oral squamous cell carcinoma

Gan Jianguo1(),Gao Pan2,Wang Xiaoyi1()   

  1. 1. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
    2. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of General and Emergency Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
  • Received:2020-06-16 Revised:2020-11-26 Online:2021-03-01 Published:2021-03-17
  • Contact: Xiaoyi Wang;
  • Supported by:
    Fund of Basic and Applied Basic Research, West China Hospital of Stomatology, Sichuan University(RD-02-201914)


Circulating tumour cells (CTCs) are tumour cells that disseminate from primary lesion into the peripheral circulating blood. Studies have linked CTCs to the early diagnosis, therapy, therapeutic evaluation and prognostic assessment of cancers, particularly breast and lung cancers. However, CTCs are seldom used in oral squamous cell carcinoma (OSCC), and their value in OSCC lacks clinical evidences. Current evidence has shown that CTCs are a relatively independent prognostic factor and one of the most important reasons of the recurrence and metastasis of OSCC. This paper reviews the current research status of CTCs in OSCC to further elaborate the mechanism of CTCs formation in OSCC and its detection techniques, explore the clinical importance of the biomarkers of OSCC-related CTCs and understand the progression and prognostic relationship between CTCs and OSCC.

Key words: circulating tumor cells, oral squamous cell carcinoma, prognosis

CLC Number: 

  • R782.2


Tab 1

Comparison of commonly used detection methods of CTCs"

方法原理 细胞活力 特异度 敏感度 是否依赖EpCAM
微流体芯片技术 是/否
[1] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020[J]. CA Cancer J Clin, 2020,70(1):7-30.
[2] Shield KD, Ferlay J, Jemal A, et al. The global incidence of lip, oral cavity, and pharyngeal cancers by subsite in 2012[J]. CA Cancer J Clin, 2017,67(1):51-64.
[3] Du M, Nair R, Jamieson L, et al. Incidence trends of lip, oral cavity, and pharyngeal cancers: global burden of disease 1990-2017[J]. J Dent Res, 2020,99(2):143-151.
pmid: 31874128
[4] Chen WQ, Zheng RS, Baade PD, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016,66(2):115-132.
[5] Saika K, Matsuda T. International comparison of lip, oral cavity and pharynx cancer incidence[J]. Jpn J Clin Oncol, 2020,50(4):479-480.
[6] Hong B, Zu YL. Detecting circulating tumor cells: current challenges and new trends[J]. Theranostics, 2013,3(6):377-394.
[7] Maly V, Maly O, Kolostova K, et al. Circulating tumor cells in diagnosis and treatment of lung cancer[J]. In Vivo, 2019,33(4):1027-1037.
pmid: 31280190
[8] Kwan TT, Bardia A, Spring LM, et al. A digital RNA signature of circulating tumor cells predicting early therapeutic response in localized and metasta-tic breast cancer[J]. Cancer Discov, 2018,8(10):1286-1299.
doi: 10.1158/2159-8290.CD-18-0432 pmid: 30104333
[9] Zhang DJ, Zhao L, Zhou PF, et al. Circulating tumor microemboli (CTM) and vimentin+ circulating tumor cells (CTCs) detected by a size-based platform predict worse prognosis in advanced colorectal cancer patients during chemotherapy[J]. Cancer Cell Int, 2017,17:6.
pmid: 28070168
[10] Marrinucci D, Bethel K, Kolatkar A, et al. Fluid bio-psy in patients with metastatic prostate, pancreatic and breast cancers[J]. Phys Biol, 2012,9(1):016003.
[11] De Craene B, Berx G. Regulatory networks defining EMT during cancer initiation and progression[J]. Nat Rev Cancer, 2013,13(2):97-110.
doi: 10.1038/nrc3447 pmid: 23344542
[12] Sánchez-Tilló E, Liu YQ, de Barrios O, et al. EMT-activating transcription factors in cancer: beyond EMT and tumor invasiveness[J]. Cell Mol Life Sci, 2012,69(20):3429-3456.
doi: 10.1007/s00018-012-1122-2 pmid: 22945800
[13] Wu MZ, Tsai YP, Yang MH, et al. Interplay between HDAC3 and WDR5 is essential for hypoxia-indu-ced epithelial-mesenchymal transition[J]. Mol Cell, 2011,43(5):811-822.
[14] Wang JQ, Yan FQ, Wang LH, et al. Identification of new hypoxia-regulated epithelial-mesenchymal transition marker genes labeled by H3K4 acetylation[J]. Genes Chromosomes Cancer, 2020,59(2):73-83.
pmid: 31408253
[15] Liu X, Li JJ, Cadilha BL, et al. Epithelial-type systemic breast carcinoma cells with a restricted mesenchymal transition are a major source of metastasis[J]. Sci Adv, 2019, 5(6): eaav4275.
[16] Massagué J, Obenauf AC. Metastatic colonization by circulating tumour cells[J]. Nature, 2016,529(7586):298-306.
doi: 10.1038/nature17038 pmid: 26791720
[17] Keller L, Pantel K. Unravelling tumour heterogenei-ty by single-cell profiling of circulating tumour cells[J]. Nat Rev Cancer, 2019,19(10):553-567.
pmid: 31455893
[18] Friedl P. Prespecification and plasticity: shifting mechanisms of cell migration[J]. Curr Opin Cell Biol, 2004,16(1):14-23.
pmid: 15037300
[19] Shigeishi H, Yokoyama S, Murodumi H, et al. Effect of hydrogel stiffness on morphology and gene expression pattern of CD44high oral squamous cell carcinoma cells[J]. Int J Clin Exp Pathol, 2019,12(8):2826-2836.
pmid: 31934119
[20] Liu YJ, Le Berre M, Lautenschlaeger F, et al. Confinement and low adhesion induce fast amoeboid migration of slow mesenchymal cells[J]. Cell, 2015,160(4):659-672.
pmid: 25679760
[21] Taddei ML, Giannoni E, Fiaschi T, et al. Anoikis: an emerging hallmark in health and diseases[J]. J Pathol, 2012,226(2):380-393.
[22] Strilic B, Offermanns S. Intravascular survival and extravasation of tumor cells[J]. Cancer Cell, 2017,32(3):282-293.
[23] In,t Veld SGJG, Wurdinger T. Tumor-educated platelets[J]. Blood, 2019,133(22):2359-2364.
doi: 10.1182/blood-2018-12-852830 pmid: 30833413
[24] Heeke S, Mograbi B, Alix-Panabières C, et al. Ne-ver travel alone: the crosstalk of circulating tumor cells and the blood microenvironment[J]. Cells, 2019,8(7):E714.
[25] Spiegel A, Brooks MW, Houshyar S, et al. Neutrophils suppress intraluminal NK cell-mediated tumor cell clearance and enhance extravasation of disseminated carcinoma cells[J]. Cancer Discov, 2016,6(6):630-649.
[26] Hu B, Rochefort H, Goldkorn A. Circulating tumor cells in prostate cancer[J]. Cancers, 2013,5(4):1676-1690.
doi: 10.3390/cancers5041676 pmid: 24305656
[27] Giesing M, Driesel G, Molitor D, et al. Molecular phenotyping of circulating tumour cells in patients with prostate cancer: prediction of distant metastases[J]. BJU Int, 2012,110(11 Pt C):E1202-E1211.
[28] Pantel K, Brakenhoff RH. Dissecting the metastatic cascade[J]. Nat Rev Cancer, 2004,4(6):448-456.
[29] Brown M, Assen FP, Leithner A, et al. Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination in mice[J]. Science, 2018,359(6382):1408-1411.
pmid: 29567714
[30] Liberko M, Kolostova K, Bobek V. Essentials of circulating tumor cells for clinical research and practice[J]. Crit Rev Oncol Hematol, 2013,88(2):338-356.
pmid: 23830807
[31] Dementeva N, Kokova D, Mayboroda OA. Current methods of the circulating tumor cells (CTC) analysis: a brief overview[J]. Curr Pharm Des, 2017,23(32):4726-4728.
pmid: 28625134
[32] Thiele JA, Bethel K, Králíčková M, et al. Circula-ting tumor cells: fluid surrogates of solid tumors[J]. Annu Rev Pathol, 2017,12:419-447.
doi: 10.1146/annurev-pathol-052016-100256 pmid: 28135562
[33] Karabacak NM, Spuhler PS, Fachin F, et al. Microfluidic, marker-free isolation of circulating tumor cells from blood samples[J]. Nat Protoc, 2014,9(3):694-710.
[34] Lin HC, Hsu HC, Hsieh CH, et al. A negative selection system PowerMag for effective leukocyte depletion and enhanced detection of EpCAM positive and negative circulating tumor cells[J]. Clin Chim Acta, 2013,419:77-84.
pmid: 23415697
[35] Sharma S, Zhuang R, Long M, et al. Circulating tumor cell isolation, culture, and downstream molecular analysis[J]. Biotechnol Adv, 2018,36(4):1063-1078.
[36] Tinhofer I, Staudte S. Circulating tumor cells as biomarkers in head and neck cancer: recent advances and future outlook[J]. Expert Rev Mol Diagn, 2018,18(10):897-906.
doi: 10.1080/14737159.2018.1522251 pmid: 30199647
[37] Hyun KA, Kim J, Gwak H, et al. Isolation and enrichment of circulating biomarkers for cancer screening, detection, and diagnostics[J]. Analyst, 2016,141(2):382-392.
[38] Park ES, Jin C, Guo Q, et al. Continuous flow deformability-based separation of circulating tumor cells using microfluidic ratchets[J]. Small, 2016,12(14):1909-1919.
doi: 10.1002/smll.201503639 pmid: 26917414
[39] Bhana S, Wang YM, Huang XH. Nanotechnology for enrichment and detection of circulating tumor cells[J]. Nanomedicine (Lond), 2015,10(12):1973-1990.
[40] Tang M, Xia HF, Xu CM, et al. Magnetic chip based extracorporeal circulation: a new tool for circulating tumor cell in vivo detection[J]. Anal Chem, 2019,91(23):15260-15266.
doi: 10.1021/acs.analchem.9b04286 pmid: 31692331
[41] Atiyah RA, Krespi YP, Hidvegi D, et al. The mechanical spread of viable tumor during surgery[J]. Otolaryngol Head Neck Surg, 1986,94(3):278-281.
pmid: 3083353
[42] Buglione M, Grisanti S, Almici C, et al. Circulating tumour cells in locally advanced head and neck cancer: preliminary report about their possible role in predicting response to non-surgical treatment and survival[J]. Eur J Cancer, 2012,48(16):3019-3026.
pmid: 22682019
[43] Bozec A, Ilie M, Dassonville O, et al. Significance of circulating tumor cell detection using the CellSearch system in patients with locally advanced head and neck squamous cell carcinoma[J]. Eur Arch Otorhinolaryngol, 2013,270(10):2745-2749.
doi: 10.1007/s00405-013-2399-y pmid: 23430081
[44] Kawada T, Takahashi H, Sakakura K, et al. Circula-ting tumor cells in patients with head and neck squamous cell carcinoma: feasibility of detection and quantitation[J]. Head Neck, 2017,39(11):2180-2186.
[45] Gröbe A, Blessmann M, Hanken, et al. Prognostic relevance of circulating tumor cells in blood and disseminated tumor cells in bone marrow of patients with squamous cell carcinoma of the oral cavity[J]. Clin Cancer Res, 2014,20(2):425-433.
pmid: 24218516
[46] Wang HM, Wu MH, Chang PH, et al. The change in circulating tumor cells before and during concurrent chemoradiotherapy is associated with survival in patients with locally advanced head and neck cancer[J]. Head Neck, 2019,41(8):2676-2687.
[47] Tinhofer I, Konschak R, Stromberger C, et al. Detection of circulating tumor cells for prediction of recurrence after adjuvant chemoradiation in locally advanced squamous cell carcinoma of the head and neck[J]. Ann Oncol, 2014,25(10):2042-2047.
doi: 10.1093/annonc/mdu271 pmid: 25057171
[48] Sun TJ, Zou K, Yuan ZW, et al. Clinicopathological and prognostic significance of circulating tumor cells in patients with head and neck cancer: a Meta-analysis[J]. Onco Targets Ther, 2017,10:3907-3916.
doi: 10.2147/OTT
[49] Xun YF, Cao Q, Zhang JX, et al. Clinicopathological and prognostic significance of circulating tumor cells in head and neck squamous cell carcinoma: a systematic review and Meta-analysis[J]. Oral Oncol, 2020,104:104638.
doi: 10.1016/j.oraloncology.2020.104638 pmid: 32182549
[50] Aceto N, Bardia A, Miyamoto DT, et al. Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis[J]. Cell, 2014,158(5):1110-1122.
pmid: 25171411
[51] Fang J, Xiao L, Zhang QY, et al. Junction plakoglobin, a potential prognostic marker of oral squamous cell carcinoma, promotes proliferation, migration and invasion[J]. J Oral Pathol Med, 2020,49(1):30-38.
pmid: 31420988
[52] Lee HY, Yu NY, Lee SH, et al. Podoplanin promotes cancer-associated thrombosis and contributes to the unfavorable overall survival in an ectopic xenograft mouse model of oral cancer[J]. Biomed J, 2020,43(2):146-162.
doi: 10.1016/ pmid: 32441651
[53] Hsieh JC, Lin HC, Huang CY, et al. Prognostic va-lue of circulating tumor cells with podoplanin expression in patients with locally advanced or metastatic head and neck squamous cell carcinoma[J]. Head Neck, 2015,37(10):1448-1455.
doi: 10.1002/hed.23779 pmid: 24844673
[54] Strati A, Koutsodontis G, Papaxoinis G, et al. Prognostic significance of PD-L1 expression on circula-ting tumor cells in patients with head and neck squamous cell carcinoma[J]. Ann Oncol, 2017,28(8):1923-1933.
pmid: 28838214
[55] Kusukawa J, Suefuji Y, Ryu F, et al. Dissemination of cancer cells into circulation occurs by incisional biopsy of oral squamous cell carcinoma[J]. J Oral Pathol Med, 2000,29(7):303-307.
doi: 10.1034/j.1600-0714.2000.290703.x pmid: 10947245
[56] Dyavanagoudar S, Kale A, Bhat K, et al. Reverse transcriptase polymerase chain reaction study to evaluate dissemination of cancer cells into circulation after incision biopsy in oral squamous cell carcinoma[J]. Indian J Dent Res, 2008,19(4):315-319.
[57] Jatana KR, Balasubramanian P, McMullen KP, et al. Effect of surgical intervention on circulating tumor cells in patients with squamous cell carcinoma of the head and neck using a negative enrichment technology[J]. Head Neck, 2016,38(12):1799-1803.
doi: 10.1002/hed.24519 pmid: 27265898
[1] Zhou Jinkuo,Zhang Jinhong,Shi Xiaojing,Liu Guangshun,Jiang Lei,Liu Qianfeng. Influences of long noncoding RNA small nucleolar RNA host gene 22 on the cell proliferation, invasion and migration of oral squamous carcinoma cells by regulating microRNA-27b-3p [J]. Int J Stomatol, 2024, 51(1): 52-59.
[2] Li Liheng,Wang Rui,Wang Xiaoming,Zhang Zhiyi,Zhang Xuan,An Feng,Wang Qin,Zhang Fan. Effects of circular RNA hsa_circ_0085576 on cell migration and invasion of oral squamous cell carcinoma by regulating the microRNA-498/B-cell-specific Moloney murine leukemia virus integration site 1 axis [J]. Int J Stomatol, 2024, 51(1): 60-67.
[3] Wu Jiamin,Xia Bin,Yang Hefeng,Xu Biao.. Research progress on cancer-associated fibroblasts in the tumor microenvironment of oral squamous cell carcinoma [J]. Int J Stomatol, 2023, 50(6): 711-717.
[4] Liu Jianglong, Tuerdi Maimaitituxun. Progress of contrast-enhanced ultrasound in the diagnosis of cervical lymph node metastasis from oral squamous cell carcinoma [J]. Int J Stomatol, 2023, 50(5): 514-520.
[5] Sheng Nanning,Wang Jue,Nan Xinrong. Research progress on mechanism and treatment of sex-determining region Y box 9 in oral squamous cell carcinoma [J]. Int J Stomatol, 2023, 50(3): 314-320.
[6] Li Tan,Liang Xin-hua.. Role of discoidin domain receptor 1 in the regulation of malignant tumor progression and therapy [J]. Int J Stomatol, 2023, 50(2): 230-236.
[7] Zhao Zhuoping,Xin Pengfei,Gao Yang,Zhang Caifeng,Zhang Kuanshou,Liu Qingmei. Research progress on the use of photothermal therapy to treat oral squamous cell carcinoma [J]. Int J Stomatol, 2022, 49(4): 462-470.
[8] Jiang Han,Shen Yingqiang,Chen Qianming. Experimental study of muscarinic receptors on the biological behavior of oral squamous cell carcinoma through Yes related protein signal [J]. Int J Stomatol, 2022, 49(2): 138-143.
[9] Bai Haoliang,Yang He,Zhao Lei. Research progress on periodontal disease risk assessment and prognosis judgment tools [J]. Int J Stomatol, 2021, 48(6): 696-702.
[10] Jiang Yulei,Xia Bin,Rao Nanquan,Yang Hefeng,Xu Biao. Exosomes mediate the malignant progression of oral squamous cell carcinoma and its application in diagnosis and treatment [J]. Int J Stomatol, 2021, 48(6): 711-717.
[11] Ma Pingchuan,Li Chunjie,Li Longjiang. Diagnosis and treatment of salivary duct carcinoma [J]. Int J Stomatol, 2021, 48(4): 459-467.
[12] Huang Junwen,Qiao Jie,Mei Zi,Chen Zhuo,Li Yang,Qiao Bin. Expression and clinical significance of lipopolysaccharide binding protein in oral squamous cell carcinoma [J]. Int J Stomatol, 2021, 48(1): 50-57.
[13] He Yuqing,Dan Hongxia,Chen Qianming. Application of photodynamic therapy for oral carcinogenesis prevention [J]. Int J Stomatol, 2020, 47(6): 669-676.
[14] Hao Fu,Ning Yi,Sun Rui,Zheng Xiaoxu. Expression and potential clinical significance of Transformer 2β in oral squamous cell carcinoma [J]. Int J Stomatol, 2020, 47(2): 159-165.
[15] Xue Lingli,Li Yadong. Survival analysis of patients with oral squamous cell carcinoma treated by radical surgery for the first time [J]. Int J Stomatol, 2020, 47(2): 166-174.
Full text



[1] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[2] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[3] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[4] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[5] . [J]. Foreign Med Sci: Stomatol, 1999, 26(05): .
[6] . [J]. Foreign Med Sci: Stomatol, 1999, 26(05): .
[7] . [J]. Foreign Med Sci: Stomatol, 1999, 26(04): .
[8] . [J]. Foreign Med Sci: Stomatol, 1999, 26(04): .
[9] . [J]. Foreign Med Sci: Stomatol, 2004, 31(02): 126 -128 .
[10] . [J]. Inter J Stomatol, 2008, 35(S1): .