口腔鳞状细胞癌患者循环肿瘤细胞上皮-间充质转化状态的研究

doi:10.13701/j.cnki.kqyxyj.2022.01.008

摘要/Abstract

摘要： 目的:探讨口腔鳞状细胞癌(oral squamous cell carcinoma, OSCC)患者与外周血循环肿瘤细胞(circulating tumor cells, CTCs)的上皮-间充质转化(epithelial-mesenchymal transition, EMT)状态的关系。方法:采用CanPatrolTM CTC-二代捕获技术联合RNA多重原位杂交分析(RNA in situ hybridization, RNA-ISH),检测32例OSCC患者术前1 d外周循环血中的肿瘤细胞。CTCs将根据EMT的相关标志物进行分型鉴定。结果:根据EMT相关标志物的表达情况,将检测出的CTCs分为上皮型CTCs(epithelial CTCs, e-CTCs),混合型CTCs(epithelial-mesenchymal-mixed CTCs, mix-CTCs)及间质型CTCs(mesenchymal CTCs, m-CTCs)。CTCs总数为198,其中e-CTCs为56(28.3%),mix-CTCs为128(64.6%),m-CTCs为14(7.1%)。每位患者的CTCs平均数值为(6.19±6.07),其中包括e-CTCs为(1.75±1.91),mix-CTCs为(4.00±5.77)和m-CTCs为(0.44±0.63)。CTCs总体数值与mix-CTCs数值相关(r²=0.908,P<0.001)。e-CTCs数值与淋巴结有无转移(r²=0.278,P<0.05)和TNM分期(r²=0.278,P<0.05)相关。CTCs总体数值与患者术后发生复发或转移(r²=0.252,P<0.05)相关。结论:mix-CTCs和e-CTCs数值可能对OSCC的进展其重要作用,CTCs可能作为OSCC预测预后的潜在指标。

关键词: 口腔鳞状细胞癌, 循环肿瘤细胞, 上皮-间充质转化

Abstract: Objective: To investigate the correlation between the status of epithelial-mesenchymal transition (EMT) of circulating tumor cells (CTCs) and oral squamous cell carcinoma (OSCC). Methods: CanPatrol^TM CTC-enrichment and situ hybridizatio (ISH) were used to isolate, identify, and classify CTCs from blood of 32 OSCC patients. Blood was collected from OSCC patients at 1 day before operation. CTCs were identified and characterized according to the EMT markers. Results: CTCs were classified into three subpopulations based on EMT markers: epithelial CTCs (e-CTCs), epithelial-mesenchymal-mixed CTCs (mix-CTC), and mesenchymal CTCs (m-CTCs). Total 198 CTCs were detected in all patients: 56 (28.3%) CTCs of them were e-CTCs, 128 (64.6%) were mix-CTCs, and 14 (7.1%) were m-CTCs. The average number of CTCs from each patient was 6.19±6.07 which included 1.75±1.91 of e-CTCs, 4.00±5.77 of mix-CTCs, and 0.44±0.63 of m---CTCs. The number of total CTCs was correlated with the number of mix-CTCs (r²=0.908, P<0.001). The number of e-CTCs was correlated with lymph node metastasis (r²=0.278, P<0.05) and TNM stage (r²=0.278, P<0.05) in this study.The number of total CTCs was correlated with recurrence or metastasi (r²=0.252, P<0.05). Conclusion: Mix-CTCs and e-CTCs might play an important role in the progression of OSCC, and the number of CTCs in OSCC might have the potential to be a predictor of prognosis.

Key words: oral squamous cell carcinoma, circulating tumor cells, epithelial-mesenchymal transition

李杨, 李雯, 陈茁, 李帅泽, 乔彬. 口腔鳞状细胞癌患者循环肿瘤细胞上皮-间充质转化状态的研究[J]. 口腔医学研究, 2022, 38(1): 34-38.

LI Yang, LI Wen, CHEN Zhuo, LI Shuaize, QIAO Bin. Detection of Epithelial-mesenchymal Transition Status of Circulating Tumor Cells in Patients with Oral Squamous Cell Carcinoma[J]. Journal of Oral Science Research, 2022, 38(1): 34-38.

参考文献

[1] Ferlay J, Colombet M, Soerjomataram I, et al. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods [J]. Int J Cancer, 2019, 144(8): 1941-1953.
[2] 于颖,曲卫国,苏颖颖,等.牙龈鳞状细胞癌浸润深度与淋巴结转移的相关性研究[J].口腔医学研究,2019,35(12):1137-1140.
[3] Jorgensen JB, Smith RB, Coughlin A, et al. Impact of PET/CT on staging and treatment of advanced head and neck squamous cell carcinoma [J]. Otolaryngol Head Neck Surg, 2019, 160(2): 261-266.
[4] Ye QW, Ling SB, Zheng SS, et al. Liquid biopsy in hepatocellular carcinoma: circulating tumor cells and circulating tumor DNA [J]. Mol Cancer, 2019, 18(1): 114.
[5] Chen J, Ye C, Dong J, et al. Metabolic classification of circulating tumor cells as a biomarker for metastasis and prognosis in breast cancer [J]. J Transl Med, 2020, 18(1): 59.
[6] Li Y J, Luo Y, Xie XQ, et al. The prognostic value of COX-2 expression on circulating tumor cells in nasopharyngeal carcinoma: A prospective analysis [J]. Radiother Oncol, 2018, 129(2): 396-402.
[7] Zhang X, Wei L, Li J, et al. Epithelial-mesenchymal transition phenotype of circulating tumor cells is associated with distant metastasis in patients with NSCLC [J]. Mol Med Rep, 2019, 19(1): 601-608.
[8] 王晓乐,贾荣.口腔鳞状细胞癌患者年龄分布与肿瘤分子标记物的关系研究[J].口腔医学研究,2019,35(3):238-241.
[9] De Craene B, Berx G. Regulatory networks defining EMT during cancer initiation and progression [J]. Nat Rev Cancer, 2013, 13(2): 97-110.
[10] Song Q, Wang B, Liu M, et al. MTA1 promotes the invasion and migration of oral squamous carcinoma by inducing epithelial-mesenchymal transition via the hedgehog signaling pathway [J]. Exp Cell Res, 2019, 382(2): 111450.
[11] Anna G, Janusz J, Agnieszka A, et al. Biomarkers of epithelial-mesenchymal transition in localized, surgically treated clear-cell renal cell carcinoma [J]. Folia Histochem Cytobiol, 2018, 56(4): 195-206.
[12] Yoshiya H, Emi T, Fumi M, et al. Analysis of circulating tumour cell and the epithelial mesenchymal transition (EMT) status during eribulin-based treatment in 22 patients with metastatic breast cancer: a pilot study [J]. J Transl Med, 2018, 16(1): 287.
[13] Li J, Liao Y, Ran Y, et al. Evaluation of sensitivity and specificity of CanPatrol^TM technology for detection of circulating tumor cells in patients with non-small cell lung cancer [J]. BMC Pulm Med, 2020, 20(1): 274.
[14] Dong YH, Yao C, Zhu Y, et al. DNA functional materials assembled from branched DNA: design, synthesis, and applications [J]. Chem Rev, 2020, 120(17): 9420-9481.
[15] Poulet G, Massias J, Taly V. Liquid biopsy: general concepts [J]. Acta Cytol, 2019, 63(6): 449-455.
[16] Lousada-Fernandez F, Rapado-Gonzalez O, Lopez-Cedrun JL, et al. Liquid biopsy in oral cancer [J]. Int J Mol Sci, 2018, 19(6):1704.
[17] Hugenschmidt H, Labori KJ, Borgen E, et al. Preoperative CTC-detection by CellSearch^® is associated with early distant metastasis and impaired survival in resected pancreatic cancer [J]. Cancers (Basel), 2021, 13(3):485.
[18] Ning D, Cui K, Liu M, et al. Comparison of CellSearch and circulating tumor cells (CTC)-biopsy systems in detecting peripheral blood circulating tumor cells in patients with gastric cancer [J]. Med Sci Monit, 2021, 27: e926565.
[19] Lozar T, Jesenko T, Kloboves Prevodnik V, et al. Preclinical and clinical evaluation of magnetic-activated cell separation technology for CTC isolation in breast cancer [J]. Front Oncol, 2020, 10: 554554.
[20] Hamid FB, Lu CT, Matos M, et al. Enumeration, characterisation and clinicopathological significance of circulating tumour cells in patients with colorectal carcinoma [J]. Cancer Genet, 2021, 254-255: 48-57.
[21] Hamid FB, Gopalan V, Matos M, et al. Genetic heterogeneity of single circulating tumour cells in colorectal carcinoma [J]. Int J Mol Sci, 2020, 21(20):7766.
[22] Grisanti S, Almici C, Consoli F, et al. Circulating tumor cells in patients with recurrent or metastatic head and neck carcinoma: prognostic and predictive significance [J]. PLoS One, 2014, 9(8): e103918.