Circulating Tumor Cell Phenotype Indicates Poor Survival and Recurrence After Surgery for Hepatocellular Carcinoma

Overview

Journal Dig Dis Sci

Specialty Gastroenterology

Date 2018 Jun 22

PMID 29926241

Citations 42

Authors

Huohui Ou

Yu Huang

Leyang Xiang

Zhanjun Chen

Yinghao Fang

Yixiong Lin

Zhonglin Cui

Sheng Yu

Xianghong Li

Dinghua Yang

Affiliations

Soon will be listed here.

Abstract

Background: Circulating tumors cells (CTCs) may be a promising prognostic marker for patients with malignant tumors. However, there are few reports regarding its value for hepatocellular carcinoma (HCC) patients.

Aims: To investigate CTCs with epithelial and mesenchymal phenotypes as a potential prognostic biomarker for HCC patients.

Methods: Peripheral blood samples were obtained from 165 HCC patients before radical surgery. CTCs were isolated via the CanPatrol CTC enrichment technique and classified using epithelial-mesenchymal transition (EMT) markers. The relationship of CTC phenotype with clinicopathological factors and HCC recurrence in patients was analyzed.

Results: CTC-positive status (count ≥ 2/5 mL) was found in 70.9% of the 165 HCC patients. Increased CTC number was more common in patients with higher AFP levels, multiple tumors, advanced TNM and BCLC staging, and presence of embolus or microembolus (P < 0.05). CTCs heterogeneity was noted using EMT markers. Mesenchymal CTCs were significantly correlated with high AFP levels, multiple tumors, advanced TNM and BCLC stage, presence of embolus or microembolus, and earlier recurrence (P < 0.05). The presence of mesenchymal CTCs predicted the shortest relapse-free survival, followed by mixed phenotypic CTCs, and then epithelial CTCs (P < 0.001).

Conclusion: CTC phenotype may serve as a prognostic indicator for HCC patients. CTCs assessment should include phenotypic identification tailored to characterize cells based on epithelial and mesenchymal markers.

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References

Kallergi G, Papadaki M, Politaki E, Mavroudis D, Georgoulias V, Agelaki S . Epithelial to mesenchymal transition markers expressed in circulating tumour cells of early and metastatic breast cancer patients. Breast Cancer Res. 2011; 13(3):R59. PMC: 3218948. DOI: 10.1186/bcr2896. View

Wu S, Liu S, Liu Z, Huang J, Pu X, Li J . Classification of circulating tumor cells by epithelial-mesenchymal transition markers. PLoS One. 2015; 10(4):e0123976. PMC: 4409386. DOI: 10.1371/journal.pone.0123976. View

Polioudaki H, Agelaki S, Chiotaki R, Politaki E, Mavroudis D, Matikas A . Variable expression levels of keratin and vimentin reveal differential EMT status of circulating tumor cells and correlation with clinical characteristics and outcome of patients with metastatic breast cancer. BMC Cancer. 2015; 15:399. PMC: 4434869. DOI: 10.1186/s12885-015-1386-7. View

Okabe H, Tsunoda S, Hosogi H, Hisamori S, Tanaka E, Tanaka S . Circulating Tumor Cells as an Independent Predictor of Survival in Advanced Gastric Cancer. Ann Surg Oncol. 2015; 22(12):3954-61. DOI: 10.1245/s10434-015-4483-6. View

Grover P, Cummins A, Price T, Roberts-Thomson I, Hardingham J . Circulating tumour cells: the evolving concept and the inadequacy of their enrichment by EpCAM-based methodology for basic and clinical cancer research. Ann Oncol. 2014; 25(8):1506-16. DOI: 10.1093/annonc/mdu018. View

Liang B, Jia C, Huang Y, He H, Li J, Liao H . TPX2 Level Correlates with Hepatocellular Carcinoma Cell Proliferation, Apoptosis, and EMT. Dig Dis Sci. 2015; 60(8):2360-72. DOI: 10.1007/s10620-015-3730-9. View

Zhao R, Cai Z, Li S, Cheng Y, Gao H, Liu F . Expression and clinical relevance of epithelial and mesenchymal markers in circulating tumor cells from colorectal cancer. Oncotarget. 2016; 8(6):9293-9302. PMC: 5354732. DOI: 10.18632/oncotarget.14065. View

Yang J, Weinberg R . Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. Dev Cell. 2008; 14(6):818-29. DOI: 10.1016/j.devcel.2008.05.009. View

Thiery J, Acloque H, Huang R, Nieto M . Epithelial-mesenchymal transitions in development and disease. Cell. 2009; 139(5):871-90. DOI: 10.1016/j.cell.2009.11.007. View

10.

Lee J, Dedhar S, Kalluri R, Thompson E . The epithelial-mesenchymal transition: new insights in signaling, development, and disease. J Cell Biol. 2006; 172(7):973-81. PMC: 2063755. DOI: 10.1083/jcb.200601018. View

11.

Liu X, Ou H, Xiang L, Li X, Huang Y, Yang D . Elevated UHRF1 expression contributes to poor prognosis by promoting cell proliferation and metastasis in hepatocellular carcinoma. Oncotarget. 2017; 8(6):10510-10522. PMC: 5354676. DOI: 10.18632/oncotarget.14446. View

12.

Shaffer D, Leversha M, Danila D, Lin O, Gonzalez-Espinoza R, Gu B . Circulating tumor cell analysis in patients with progressive castration-resistant prostate cancer. Clin Cancer Res. 2007; 13(7):2023-9. DOI: 10.1158/1078-0432.CCR-06-2701. View

13.

de Albuquerque A, Kubisch I, Breier G, Stamminger G, Fersis N, Eichler A . Multimarker gene analysis of circulating tumor cells in pancreatic cancer patients: a feasibility study. Oncology. 2012; 82(1):3-10. DOI: 10.1159/000335479. View

14.

Chen W, Zheng R, Zeng H, Zhang S, He J . Annual report on status of cancer in China, 2011. Chin J Cancer Res. 2015; 27(1):2-12. PMC: 4329176. DOI: 10.3978/j.issn.1000-9604.2015.01.06. View

15.

Li Y, Cheng X, Chen Z, Liu Y, Liu Z, Xu S . Circulating tumor cells in peripheral and pulmonary venous blood predict poor long-term survival in resected non-small cell lung cancer patients. Sci Rep. 2017; 7(1):4971. PMC: 5503943. DOI: 10.1038/s41598-017-05154-x. View

16.

Qiao Y, Li J, Shi C, Wang W, Qu X, Xiong M . Prognostic value of circulating tumor cells in the peripheral blood of patients with esophageal squamous cell carcinoma. Onco Targets Ther. 2017; 10:1363-1373. PMC: 5344437. DOI: 10.2147/OTT.S129004. View

17.

Nieto M, Huang R, Jackson R, Thiery J . EMT: 2016. Cell. 2016; 166(1):21-45. DOI: 10.1016/j.cell.2016.06.028. View

18.

Qin L, Tang Z . Recent progress in predictive biomarkers for metastatic recurrence of human hepatocellular carcinoma: a review of the literature. J Cancer Res Clin Oncol. 2004; 130(9):497-513. DOI: 10.1007/s00432-004-0572-9. View

19.

Tjensvoll K, Nordgard O, Smaaland R . Circulating tumor cells in pancreatic cancer patients: methods of detection and clinical implications. Int J Cancer. 2013; 134(1):1-8. DOI: 10.1002/ijc.28134. View

20.

Abrahamsson J, Aaltonen K, Engilbertsson H, Liedberg F, Patschan O, Ryden L . Circulating tumor cells in patients with advanced urothelial carcinoma of the bladder: Association with tumor stage, lymph node metastases, FDG-PET findings, and survival. Urol Oncol. 2017; 35(10):606.e9-606.e16. DOI: 10.1016/j.urolonc.2017.05.021. View