Prognostic Value of Liver Cancer CTCs Isolated by a Novel Microfluidic Platform

This study aims to isolate CTCs in peripheral venous blood of liver cancer patients by inertial focusing principle-based microfluidic device, determine the relationship between the number of CTCs and patient prognosis and treatment response, detect mutation, copy number variation and mutation load in CTC cells and corresponding tissues using single-cell whole genome sequencing technology, and use bioinformatics analysis of CTC heterogeneity and its relationship with clinical outcome. In addition, the culture of CTCs in vitro was explored by organoid culture or sphere culture in order to obtain CTCs cell lines to reveal the metastatic mechanisms of HCC. The partner of this project is Cellomics International Limited, which could provide Cellomics CTC-100 cell sorter and related consumables for this project. Peripheral venous blood from about 300 patients with initial liver cancer will be collected, and CTCs cells will be sorted in 8ml of each patient and typed according to protein expression. Clinical data, treatment effect and survival time of patients will be collected, and finally the relationship between the number of CTCs and subgroup with treatment response and patient prognosis will be analyzed. Uncovering the genomic characteristics of CTCs of HCC provides a new basis for the precise treatment of HCC. The new diagnostic markers for Hcancer were found by miRNA expression spectrum chip and metabolomic testing.In vitro culture methods and cellular characteristics of HCC circulating tumor cells were preliminarily explored.

Sex

All

Minimum age

18 Years

Maximum age

70 Years

Inclusion Criteria:

* confirmed by imaging and serological examination for benign liver cancer;
* patients without any previous treatment;
* informed consent;
* age: 18 years or older (adult).

Exclusion Criteria:

* with other malignancies;
* metastatic liver tumors;
* with major organic lesions;
* with acute complications such as acute liver failure, massive gastrointestinal bleeding and so on.

• RESULTLlovet JM, Kelley RK, Villanueva A, Singal AG, Pikarsky E, Roayaie S, Lencioni R, Koike K, Zucman-Rossi J, Finn RS. Hepatocellular carcinoma. Nat Rev Dis Primers. 2021 Jan 21;7(1):6. doi: 10.1038/s41572-020-00240-3. PMID 33479224
• RESULTAhn JC, Teng PC, Chen PJ, Posadas E, Tseng HR, Lu SC, Yang JD. Detection of Circulating Tumor Cells and Their Implications as a Biomarker for Diagnosis, Prognostication, and Therapeutic Monitoring in Hepatocellular Carcinoma. Hepatology. 2021 Jan;73(1):422-436. doi: 10.1002/hep.31165. Epub 2021 Jan 18. PMID 32017145
• RESULTChen VL, Xu D, Wicha MS, Lok AS, Parikh ND. Utility of Liquid Biopsy Analysis in Detection of Hepatocellular Carcinoma, Determination of Prognosis, and Disease Monitoring: A Systematic Review. Clin Gastroenterol Hepatol. 2020 Dec;18(13):2879-2902.e9. doi: 10.1016/j.cgh.2020.04.019. Epub 2020 Apr 11. PMID 32289533
• RESULTZhu Z, Qiu S, Shao K, Hou Y. Progress and challenges of sequencing and analyzing circulating tumor cells. Cell Biol Toxicol. 2018 Oct;34(5):405-415. doi: 10.1007/s10565-017-9418-5. Epub 2017 Nov 22. PMID 29168077
• RESULTCourt CM, Hou S, Liu L, Winograd P, DiPardo BJ, Liu SX, Chen PJ, Zhu Y, Smalley M, Zhang R, Sadeghi S, Finn RS, Kaldas FM, Busuttil RW, Zhou XJ, Tseng HR, Tomlinson JS, Graeber TG, Agopian VG. Somatic copy number profiling from hepatocellular carcinoma circulating tumor cells. NPJ Precis Oncol. 2020 Jul 2;4:16. doi: 10.1038/s41698-020-0123-0. eCollection 2020. PMID 32637655
• RESULTPantel K, Hille C, Scher HI. Circulating Tumor Cells in Prostate Cancer: From Discovery to Clinical Utility. Clin Chem. 2019 Jan;65(1):87-99. doi: 10.1373/clinchem.2018.287102. PMID 30602476
• RESULTChen W, Zhang J, Huang L, Chen L, Zhou Y, Tang D, Xie Y, Wang H, Huang C. Detection of HER2-positive Circulating Tumor Cells Using the LiquidBiopsy System in Breast Cancer. Clin Breast Cancer. 2019 Feb;19(1):e239-e246. doi: 10.1016/j.clbc.2018.10.009. Epub 2018 Nov 1.