肝癌循环肿瘤细胞研究进展
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摘要
循环肿瘤细胞(CTC)作为一种可靠的生物标志物,具有无创、检测特异性高等优点。近年来,CTC检测已经广泛用于肝癌诊断,包括肝癌的早期诊断、复发诊断及预后判断等方面。综述CTC转移机制及转移特征、检测技术(包括物理检测和生物检测)的更新及综合应用,结合其在肝癌诊断中的相关研究进展,并对其应用前景进行展望。
Circulating tumor cells(CTC), as a reliable biomarker, have the advantages of noninvasive and high detection specificity. In recent years, CTC has already been widely used in management of hepatocellular carcinoma(HCC), including early diagnosis, recurrence diagnosis and prognosis estimation and so on. In this article, we reviewed the related researches in HCC diagnosis and introduced the mechanism and characteristics of CTC transfer, the latest detection techniques(including physical detection and biological detection) and their applications, and prospective of CTC.
Circulating tumor cells(CTC), as a reliable biomarker, have the advantages of noninvasive and high detection specificity. In recent years, CTC has already been widely used in management of hepatocellular carcinoma(HCC), including early diagnosis, recurrence diagnosis and prognosis estimation and so on. In this article, we reviewed the related researches in HCC diagnosis and introduced the mechanism and characteristics of CTC transfer, the latest detection techniques(including physical detection and biological detection) and their applications, and prospective of CTC.
引文
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[28]Yao M,Yao DF,Bian YZ,et al.Values of circulating GPC-3 mRNAand alpha-fetoprotein in detecting patients with hepatocellular carcinoma[J].Hepatobiliary Pancreat Dis Int,2013,12:171-179.
[2]Yin CQ,Yuan CH,Qu Z,et al.Liquid biopsy of hepatocellular carcinoma:circulating tumor-derived biomarkers[J].Dis Markers,2016,20:427-449.
[3]Van Meer S,De Man RA,Coenraad MJ,et al.Surveillance for hepatocellular carcinoma is associated with increased survival:Results from a large cohort in the Netherlands[J].J Hepatol,2015,63:1156-1163.
[4]Sun Y,Guo W,Xu Y,et al.Circulating tumors cells from different vascular sites exhibit spatial heterogeneity in epithelial and mesenchymal composition and distinct clinical significance in hepatocellular carcinoma[J].Clin Cancer Res,2018,24:547-559.
[5]Hong Y,Li Z,Zhang Q.A circulating tumor cell cluster-based model for tumor metastasis(Hypothesis)[J].Oncol Lett,2016,12:4891-4895.
[6]Hou JM,Krebs MG,Lancashire L,et al.Clinical significance and molecular characteristics of circulating tumor cells and circulating tumor microemboli in patients with small-cell lung cancer[J].J Clin Oncol,2012,30:525-532.
[7]Liu X,Li C,Li J,et al.Detection of CTCs in portal vein was associated with intrahepatic metastases and prognosis in patients with advanced pancreatic cancer[J].J Cancer,2018,9:2038-2045.
[8]Court CM,Hou S,Winograd P,et al.A novel multimarker assay for the phenotypic profiling of circulating tumor cells in hepatocellular carcinoma[J].Liver Transpl,2018,27:946-960.
[9]Aceto N,Bardia A,Miyamoto DT,et al.Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis[J].Cell,2014,158:1110-1122.
[10]Low WS,Wan Abas WA.Benchtop technologies for circulating tumor cells separation based on biophysical properties[J].Biomed Res Int,2015,20:239-262.
[11]Coumans FA,Van Dalum G,Beck M,et al.Filter characteristics influencing circulating tumor cell enrichment from whole blood[J].PLoS One,2013,8:717-727.
[12]Su YH,Kim AK,Jain S.Liquid biopsies for hepatocellular carcinoma[J].Transl Res,2018,22:89-96.
[13]Morris KL,Tugwood JD,Khoja L,et al.Circulating biomarkers in hepatocellular carcinoma[J].Cancer Chemother Pharmacol,2014,74:323-332.
[14]Krebs MG,Metcalf RL,Carter L,et al.Molecular analysis of circulating tumour cells-biology and biomarkers[J].Chin Ger J Clin Oncol,2014,11:129-144.
[15]Sheng W,Ogunwobi OO,Chen T,et al.Capture,release and culture of circulating tumor cells from pancreatic cancer patients using an enhanced mixing chip[J].Lab Chip,2014,14:89-98.
[16]Mandair D,Vesely C,Ensell L,et al.A comparison of CellCollector with CellSearch in patients with neuroendocrine tumours[J].Endocr Relat Cancer,2016,23:29-32.
[17]Lustberg MB,Balasubramanian P,Miller B,et al.Heterogeneous atypical cell populations are present in blood of metastatic breast cancer patients[J].Breast Cancer Res,2014,16:23.
[18]Torga G,Pienta KJ.Patient-paired sample congruence between 2commercial liquid biopsy tests[J].JAMA Oncol,2018,4:868-870.
[19]Myung JH,Park SJ,Wang AZ,et al.Integration of biomimicry and nanotechnology for significantly improved detection of circulating tumor cells(CTCs)[J].Adv Drug Deliv Rev,2018,125:36-47.
[20]Wang Z,Luo L,Cheng Y,et al.Correlation between postoperative early recurrence of hepatocellular carcinoma and mesenchymal circulating tumor cells in peripheral blood[J].J Gastrointest Surg,2018,22:633-639.
[21]Liu Z,Guo W,Zhang D,et al.Circulating tumor cell detection in hepatocellular carcinoma based on karyoplasmic ratios using imaging flow cytometry[J].Sci Rep,2016,6:398-408.
[22]Kalinich M,Bhan I,Kwan TT,et al.An RNA-based signature enables high specificity detection of circulating tumor cells in hepatocellular carcinoma[J].Proc Natl Acad Sci USA,2017,114:1123-1128.
[23]Okajima W,Komatsu S,Ichikawa D,et al.Liquid biopsy in patients with hepatocellular carcinoma:circulating tumor cells and cell-free nucleic acids[J].World J Gastroenterol,2017,23:5650-5668.
[24]Kourou K,Exarchos TP,Exarchos KP,et al.Machine learning applications in cancer prognosis and prediction[J].Comput Struct Biotechnol J,2015,13:8-17.
[25]Sun C,Liao W,Deng Z,et al.The diagnostic value of assays for circulating tumor cells in hepatocellular carcinoma:a meta-analysis[J].Medicine(Baltimore),2017,96:75-83.
[26]Sun YF,Xu Y,Yang XR,et al.Circulating stem cell-like epithelial cell adhesion molecule-positive tumor cells indicate poor prognosis of hepatocellular carcinoma after curative resection[J].Hepatology,2013,57:1458-1468.
[27]Guo W,Yang XR,Sun YF,et al.Clinical significance of EpCAMmRNA-positive circulating tumor cells in hepatocellular carcinoma by an optimized negative enrichment and qRT-PCR-based platform[J].Clin Cancer Res,2014,20:4794-4805.
[28]Yao M,Yao DF,Bian YZ,et al.Values of circulating GPC-3 mRNAand alpha-fetoprotein in detecting patients with hepatocellular carcinoma[J].Hepatobiliary Pancreat Dis Int,2013,12:171-179.