Multigene Profiling of Circulating Tumor Cells in Esophageal Squamous Cell Carcinoma Identifies Prognostic Cancer Driver Genes Associated with Epithelial-Mesenchymal-Transition Progression and Chemoresistance

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2023 Nov 25

PMID 38001588

Authors

Zhen Tan

Josephine Mun-Yee Ko

Valen Zhuoyou Yu

Ka-On Lam

Dora Lai-Wan Kwong

Ian Yu-Hong Wong

Fion Siu-Yin Chan

Claudia Lai-Yin Wong

Kwan-Kit Chan

Tsz-Ting Law

Faith Sin-Fai Choy

Hoi-Yan Ng

Simon Ying-Kit Law

Maria Li Lung

Affiliations

Soon will be listed here.

Abstract

We investigated the clinical significance of CTCs in cancer progression by detecting multiple cancer driver genes associated with epithelial-to-mesenchymal transition (EMT) at the transcript level. The 10-gene panel, comprising , , , , , , , , , and , was established for characterizing CTCs from mouse ESCC xenograft models and clinical ESCC peripheral blood (PB) samples. Correlations between gene expression in CTCs from PB samples ( = 77) and clinicopathological features in ESCC patients ( = 55) were examined. The presence of CTCs at baseline was significantly correlated with tumor size ( = 0.031). The CTC-high patients were significantly correlated with advanced cancer stages ( = 0.013) and distant metastasis ( = 0.029). High mRNA levels of (Hazard Ratio (HR) = 5.44, = 0.007), (HR = 6.67, < 0.001), (HR = 2.63, = 0.034), and (HR = 2.53, = 0.041) at baseline were significantly associated with a shorter overall survival (OS) in ESCC patients. This study also revealed that facilitates EMT and enhances malignant potential by promoting tumor migration, invasion, and cisplatin chemoresistance through the axis in ESCC, highlighting the prognostic and therapeutic potential of in clinical ESCC treatment.

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References

Matsushita D, Uenosono Y, Arigami T, Yanagita S, Nishizono Y, Hagihara T . Clinical Significance of Circulating Tumor Cells in Peripheral Blood of Patients with Esophageal Squamous Cell Carcinoma. Ann Surg Oncol. 2015; 22(11):3674-80. PMC: 4565870. DOI: 10.1245/s10434-015-4392-8. View

Sung H, Ferlay J, Siegel R, Laversanne M, Soerjomataram I, Jemal A . Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3):209-249. DOI: 10.3322/caac.21660. View

Cheng G, Chan J, Wang Q, Zhang W, Sun C, Wang L . Twist transcriptionally up-regulates AKT2 in breast cancer cells leading to increased migration, invasion, and resistance to paclitaxel. Cancer Res. 2007; 67(5):1979-87. DOI: 10.1158/0008-5472.CAN-06-1479. View

Shah M . Update on metastatic gastric and esophageal cancers. J Clin Oncol. 2015; 33(16):1760-9. DOI: 10.1200/JCO.2014.60.1799. View

Ko J, Ng H, Lam K, Chiu K, Kwong D, Lo A . Liquid Biopsy Serial Monitoring of Treatment Responses and Relapse in Advanced Esophageal Squamous Cell Carcinoma. Cancers (Basel). 2020; 12(6). PMC: 7352685. DOI: 10.3390/cancers12061352. View

Warkiani M, Khoo B, Wu L, Tay A, Bhagat A, Han J . Ultra-fast, label-free isolation of circulating tumor cells from blood using spiral microfluidics. Nat Protoc. 2015; 11(1):134-48. DOI: 10.1038/nprot.2016.003. View

Sun Q, Wang Y, Officer A, Pecknold B, Lee G, Harismendy O . Stem-like breast cancer cells in the activated state resist genetic stress via TGFBI-ZEB1. NPJ Breast Cancer. 2022; 8(1):5. PMC: 8758745. DOI: 10.1038/s41523-021-00375-w. View

Markou A, Lazaridou M, Paraskevopoulos P, Chen S, Swierczewska M, Budna J . Multiplex Gene Expression Profiling of In Vivo Isolated Circulating Tumor Cells in High-Risk Prostate Cancer Patients. Clin Chem. 2017; 64(2):297-306. DOI: 10.1373/clinchem.2017.275503. View

Zhang S, Wu T, Peng X, Liu J, Liu F, Wu S . Mesenchymal phenotype of circulating tumor cells is associated with distant metastasis in breast cancer patients. Cancer Manag Res. 2017; 9:691-700. PMC: 5703158. DOI: 10.2147/CMAR.S149801. View

10.

Lei L, Yu V, Ko J, Ning L, Lung M . FANCD2 Confers a Malignant Phenotype in Esophageal Squamous Cell Carcinoma by Regulating Cell Cycle Progression. Cancers (Basel). 2020; 12(9). PMC: 7565464. DOI: 10.3390/cancers12092545. View

11.

Ujiie D, Matsumoto T, Endo E, Okayama H, Fujita S, Kanke Y . Circulating tumor cells after neoadjuvant chemotherapy are related with recurrence in esophageal squamous cell carcinoma. Esophagus. 2021; 18(3):566-573. DOI: 10.1007/s10388-021-00829-x. View

12.

Yin X, Yuan X, Xue J, Wang R, Zhang Z, Tong J . Clinical significance of carcinoembryonic antigen-, cytokeratin 19-, or survivin-positive circulating tumor cells in the peripheral blood of esophageal squamous cell carcinoma patients treated with radiotherapy. Dis Esophagus. 2012; 25(8):750-6. DOI: 10.1111/j.1442-2050.2012.01326.x. View

13.

Papadaki M, Mala A, Merodoulaki A, Vassilakopoulou M, Mavroudis D, Agelaki S . Investigating the Role of CTCs with Stem/EMT-like Features in Metastatic Breast Cancer Patients Treated with Eribulin Mesylate. Cancers (Basel). 2022; 14(16). PMC: 9405936. DOI: 10.3390/cancers14163903. View

14.

Roberts C, Tran M, Pitruzzello M, Wen W, Loeza J, Dellinger T . TWIST1 drives cisplatin resistance and cell survival in an ovarian cancer model, via upregulation of GAS6, L1CAM, and Akt signalling. Sci Rep. 2016; 6:37652. PMC: 5120297. DOI: 10.1038/srep37652. View

15.

Joosse S, Gorges T, Pantel K . Biology, detection, and clinical implications of circulating tumor cells. EMBO Mol Med. 2014; 7(1):1-11. PMC: 4309663. DOI: 10.15252/emmm.201303698. View

16.

Pastushenko I, Blanpain C . EMT Transition States during Tumor Progression and Metastasis. Trends Cell Biol. 2018; 29(3):212-226. DOI: 10.1016/j.tcb.2018.12.001. View

17.

Brabletz S, Schuhwerk H, Brabletz T, Stemmler M . Dynamic EMT: a multi-tool for tumor progression. EMBO J. 2021; 40(18):e108647. PMC: 8441439. DOI: 10.15252/embj.2021108647. View

18.

Hofman V, Ilie M, Long E, Selva E, Bonnetaud C, Molina T . Detection of circulating tumor cells as a prognostic factor in patients undergoing radical surgery for non-small-cell lung carcinoma: comparison of the efficacy of the CellSearch Assay™ and the isolation by size of epithelial tumor cell method. Int J Cancer. 2010; 129(7):1651-60. DOI: 10.1002/ijc.25819. View

19.

Su P, Wu M, Wang H, Lee C, Huang W, Wu C . Circulating Tumour Cells as an Independent Prognostic Factor in Patients with Advanced Oesophageal Squamous Cell Carcinoma Undergoing Chemoradiotherapy. Sci Rep. 2016; 6:31423. PMC: 4987675. DOI: 10.1038/srep31423. View

20.

Morgan E, Soerjomataram I, Rumgay H, Coleman H, Thrift A, Vignat J . The Global Landscape of Esophageal Squamous Cell Carcinoma and Esophageal Adenocarcinoma Incidence and Mortality in 2020 and Projections to 2040: New Estimates From GLOBOCAN 2020. Gastroenterology. 2022; 163(3):649-658.e2. DOI: 10.1053/j.gastro.2022.05.054. View