循环肿瘤细胞在肺癌中的临床应用进展

摘要/Abstract

摘要：

肺癌是全球发病率及死亡率最高的肿瘤，我国肺癌的发病例数也在逐年升高，严重威胁人类的生命健康。循环肿瘤细胞（CTC）是指从原发肿瘤组织或转移灶中脱落下来进入外周血的肿瘤细胞，是肿瘤转移的关键。目前CTC检测的方法多种多样，各有利弊。近年来全球在CTC应用于肺癌中的研究层出不穷。进一步探讨CTC在肺癌中的临床应用进展，可为CTC在肺癌的早期诊断、疗效评估及预后监测等方面的作用提供新的依据。

关键词:肿瘤细胞，循环,肺肿瘤,液体活组织检查,诊断,预后

Abstract:

Lung cancer is the cancer with the highest incidence of morbidity and mortality in the world， and the number of lung cancer cases in China is also increasing year by year， which seriously threatens the life and health of human beings. Circulating tumor cells （CTCs） refer to the tumor cell that falls off from primary tumor tissue or metastatic focus into the peripheral blood， which is the key to tumor metastasis. Currently， there are various methods for CTCs testing， each with its own advantages and disadvantages. In recent years， there have been numerous studies on the application of CTCs in lung cancer around the world. Further exploration of the progress of clinical application of CTCs in lung cancer can provide a new basis for the role of CTCs in early diagnosis， efficacy assessment and prognostic monitoring of lung cancer.

Key words:Neoplastic cells， circulating,Lung neoplasms,Liquid biopsy,Diagnosis,Prognosis

陈丹蕾, 邓隽军, 李淼. 循环肿瘤细胞在肺癌中的临床应用进展[J]. 国际肿瘤学杂志, 2025, 52(2): 119-123.

Chen Danlei, Deng Junjun, Li Miao. Progress of clinical application of circulating tumor cells in lung cancer[J]. Journal of International Oncology, 2025, 52(2): 119-123.

参考文献40

[1]	Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].CA Cancer J Clin,2021,71(3): 209-249. DOI:10.3322/caac.21660.
[2]	Chen P, Liu Y, Wen Y, et al. Non-small cell lung cancer in China[J].Cancer Commun (Lond),2022,42(10): 937-970. DOI:10.1002/cac2.12359.
[3]	Miller KD, Nogueira L, Devasia T, et al. Cancer treatment and survivorship statistics, 2022[J].CA Cancer J Clin,2022,72(5): 409-436. DOI:10.3322/caac.21731.
[4]	Saltos A, Shafique M, Chiappori A. Update on the biology, management, and treatment of small cell lung cancer (SCLC)[J].Front Oncol,2020,10: 1074. DOI:10.3389/fonc.2020.01074. pmid:32766139
[5]	Lin D, Shen L, Luo M, et al. Circulating tumor cells: biology and clinical significance[J].Signal Transduct Target Ther,2021,6(1): 404. DOI:10.1038/s41392-021-00817-8.
[6]	Nikanjam M, Kato S, Kurzrock R. Liquid biopsy: current technology and clinical applications[J].J Hematol Oncol,2022,15(1): 131. DOI:10.1186/s13045-022-01351-y.
[7]	Li W, Liu JB, Hou LK, et al. Liquid biopsy in lung cancer: significance in diagnostics, prediction, and treatment monitoring[J].Mol Cancer,2022,21(1): 25. DOI:10.1186/s12943-022-01505-z. pmid:35057806
[8]	Chang Y, Wang Y, Li B, et al. Whole-exome sequencing on circulating tumor cells explores platinum-drug resistance mutations in advanced non-small cell lung cancer[J].Front Genet,2021,12: 722078. DOI:10.3389/fgene.2021.722078.
[9]	Ju L, Yang J, Zhai C, et al. Survival, chemotherapy and chemosensitivity predicted by CTC cultured in vitro of SCLC patients[J].Front Oncol,2021,11: 683318. DOI:10.3389/fonc.2021.683318.
[10]	Guan Y, Xu F, Tian J, et al. Pathology of circulating tumor cells and the available capture tools (Review)[J].Oncol Rep,2020,43(5): 1355-1364. DOI:10.3892/or.2020.7533. pmid:32323847
[11]	Allard WJ, Matera J, Miller MC, et al. Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases[J].Clin Cancer Res,2004,10(20): 6897-6904. DOI:10.1158/1078-0432.CCR-04-0378. pmid:15501967
[12]	Yousefi M, Ghaffari P, Nosrati R, et al. Prognostic and therapeutic significance of circulating tumor cells in patients with lung cancer[J].Cell Oncol (Dordr),2020,43(1): 31-49. DOI:10.1007/s13402-019-00470-y.
[13]	Ilie M, Hofman V, Long-Mira E, et al. "Sentinel" circulating tumor cells allow early diagnosis of lung cancer in patients with chronic obstructive pulmonary disease[J].PLoS One,2014,9(10): e111597. DOI:10.1371/journal.pone.0111597.
[14]	Xie J, Hu B, Gong Y, et al. A comparative study on ctDNA and tumor DNA mutations in lung cancer and benign cases with a high number of CTCs and CTECs[J].J Transl Med,2023,21(1): 873. DOI:10.1186/s12967-023-04746-8. pmid:38041139
[15]	Liu C, Chen H, Sun T, et al. The value of circulating tumor cells with positive centromere probe 8 in the diagnosis of small pulmonary nodules[J].Transl Oncol,2021,14(5): 101052. DOI:10.1016/j.tranon.2021.101052.
[16]	Manjunath Y, Upparahalli SV, Suvilesh KN, et al. Circulating tumor cell clusters are a potential biomarker for detection of non-small cell lung cancer[J].Lung Cancer,2019,134: 147-150. DOI:10.1016/j.lungcan.2019.06.016. pmid:31319973
[17]	Zhou Q, Geng Q, Wang L, et al. Value of folate receptor-positive circulating tumour cells in the clinical management of indeterminate lung nodules: a non-invasive biomarker for predicting malignancy and tumour invasiveness[J].EBioMedicine,2019,41: 236-243. DOI:10.1016/j.ebiom.2019.02.028. pmid:30872130
[18]	Zhao Q, Yuan Z, Wang H, et al. Role of circulating tumor cells in diagnosis of lung cancer: a systematic review and meta-analysis[J].J Int Med Res,2021,49(3): 300060521994926. DOI:10.1177/0300060521994926.
[19]	Tamminga M, de Wit S, Schuuring E, et al. Circulating tumor cells in lung cancer are prognostic and predictive for worse tumor response in both targeted-and chemotherapy[J].Transl Lung Cancer Res,2019,8(6): 854-861. DOI:10.21037/tlcr.2019.11.06.
[20]	Wang Z, Zhang XC, Feng WN, et al. Circulating tumor cells dynamics during chemotherapy predict survival and response in advanced non-small-cell lung cancer patients[J].Ther Adv Med Oncol,2023,15: 17588359231167818. DOI:10.1177/17588359231167818.
[21]	Liu J, Liu Y, Gu C, et al. Longitudinal change of circulating tumor cells during chemoradiation and its correlation with prognosis in advanced nonsmall-cell lung cancer patients[J].Cancer Biother Radiopharm,2023,38(5): 305-312. DOI:10.1089/cbr.2020.4096.
[22]	Xu Y, Ren X, Jiang T, et al. Circulating tumor cells (CTCs) and hTERT gene expression in CTCs for radiotherapy effect with lung cancer[J].BMC Cancer,2023,23(1): 475. DOI:10.1186/s12885-023-10979-z. pmid:37226235
[23]	Punnoose EA, Atwal S, Liu W, et al. Evaluation of circulating tumor cells and circulating tumor DNA in non-small cell lung cancer: association with clinical endpoints in a phase Ⅱ clinical trial of pertuzumab and erlotinib[J].Clin Cancer Res,2012,18(8): 2391-2401. DOI:10.1158/1078-0432.CCR-11-3148.
[24]	Kallergi G, Kontopodis E, Ntzifa A, et al. Effect of osimertinib on CTCs and ctDNA in EGFR mutant non-small cell lung cancer patients: the prognostic relevance of liquid biopsy[J].Cancers (Basel),2022,14(6): 1574. DOI:10.3390/cancers14061574.
[25]	Pailler E, Faugeroux V, Oulhen M, et al. Acquired resistance mutations to ALK inhibitors identified by single circulating tumor cell sequencing in ALK-rearranged non-small-cell lung cancer[J].Clin Cancer Res,2019,25(22): 6671-6682. DOI:10.1158/1078-0432.CCR-19-1176. pmid:31439588
[26]	Isobe K, Yoshizawa T, Sekiya M, et al. Quantification of BIM mRNA in circulating tumor cells of osimertinib-treated patients with EGFR mutation-positive lung cancer[J].Respir Investig,2021,59(4): 535-544. DOI:10.1016/j.resinv.2021.03.010. pmid:33934994
[27]	Pharaon R, Koczywas MA, Salgia S, et al. Biomarkers in immunotherapy: literature review and future directions[J].J Thorac Dis,2020,12(9): 5119-5127. DOI:10.21037/jtd.2020.04.15. pmid:33145089
[28]	蔡刚祥, 李境, 许斌. 肺癌新辅助免疫治疗研究进展[J].国际肿瘤学杂志,2022,49(6): 366-370. DOI:10.3760/cma.j.cn371439-20220323-00070.
[29]	Zhang Y, Zhang Z. The history and advances in cancer immunotherapy: understanding the characteristics of tumor-infiltrating immune cells and their therapeutic implications[J].Cell Mol Immunol,2020,17(8): 807-821. DOI:10.1038/s41423-020-0488-6. pmid:32612154
[30]	Kloten V, Lampignano R, Krahn T, et al. Circulating tumor cell PD-L1 expression as biomarker for therapeutic efficacy of immune checkpoint inhibition in NSCLC[J].Cells,2019,8(8): 809. DOI:10.3390/cells8080809.
[31]	Spiliotaki M, Neophytou CM, Vogazianos P, et al. Dynamic monitoring of PD-L1 and Ki67 in circulating tumor cells of metastatic non-small cell lung cancer patients treated with pembrolizumab[J].Mol Oncol,2023,17(5): 792-809. DOI:10.1002/1878-0261.13317.
[32]	Ikeda M, Koh Y, Teraoka S, et al. Longitudinal evaluation of PD-L1 expression on circulating tumor cells in non-small cell lung cancer patients treated with nivolumab[J].Cancers (Basel),2021,13(10): 2290. DOI:10.3390/cancers13102290.
[33]	Zhu HH, Liu YT, Feng Y, et al. Circulating tumor cells (CTCs)/circulating tumor endothelial cells (CTECs) and their subtypes in small cell lung cancer: predictors for response and prognosis[J].Thorac Cancer,2021,12(20): 2749-2757. DOI:10.1111/1759-7714.14120.
[34]	Frick MA, Feigenberg SJ, Jean-Baptiste SR, et al. Circulating tumor cells are associated with recurrent disease in patients with early-stage non-small cell lung cancer treated with stereotactic body radiotherapy[J].Clin Cancer Res,2020,26(10): 2372-2380. DOI:10.1158/1078-0432.CCR-19-2158. pmid:31969332
[35]	徐静, 何靓, 钱慧珠, 等. 循环肿瘤细胞检测在EGFR合并TP53突变的晚期非小细胞肺癌一代EGFR-TKI治疗中的疗效评价[J].医学研究生学报,2022,35(3): 278-282. DOI:10.16571/j.cnki.1008-8199.2022.03.009.
[36]	Pantazaka E, Ntzifa A, Roumeliotou A, et al. PD-L1/pS6 in circulating tumor cells (CTCs) during osimertinib treatment in patients with non-small cell lung cancer (NSCLC)[J].Biomedicines,2022,10(8): 1893. DOI:10.3390/biomedicines10081893.
[37]	Zhou Q, Liu X, Li J, et al. Circulating tumor cells PD-L1 expression detection and correlation of therapeutic efficacy of immune checkpoint inhibition in advanced non-small-cell lung cancer[J].Thorac Cancer,2023,14(5): 470-478. DOI:10.1111/1759-7714.14767. pmid:36630992
[38]	Castello A, Carbone FG, Rossi S, et al. Circulating tumor cells and metabolic parameters in NSCLC patients treated with checkpoint inhibitors[J].Cancers (Basel),2020,12(2): 487. DOI:10.3390/cancers12020487.
[39]	Yang D, Yang X, Li Y, et al. Clinical significance of circulating tumor cells and metabolic signatures in lung cancer after surgical removal[J].J Transl Med,2020,18(1): 243. DOI:10.1186/s12967-020-02401-0. pmid:32552826
[40]	Li Z, Xu K, Tartarone A, et al. Circulating tumor cells can predict the prognosis of patients with non-small cell lung cancer after resection: a retrospective study[J].Transl Lung Cancer Res,2021,10(2): 995-1006. DOI:10.21037/tlcr-21-149.