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Liver cancer is one of the most common malignant tumors worldwide with high morbidity and mortality, and hepatocellular carcinoma (HCC) is the main histological subtype. So far, liver resection is the most effective treatment but the postoperative recurrence rate is high at five years, and the prognosis is difficult to estimate. Microvascular invasion (MVI) and postoperative minimal residual disease (MRD) are crucial prognostic factors for patients undergoing hepatectomy. Although many laboratory and imaging methods have been established to estimate the recurrence risk, their stability and accuracy are still not high. To date, no unified conclusion is achieved. It's eagerly to screen out a batch of individualized staging and prognosis-related biological indicators for early warning and prediction of prognosis, having good stability and high precision. Circulating cell-free DNA (cfDNA) molecular detection technology is an emerging detection technology of tumor gene profiling in recent years, which can be used to predict and monitor tumor recurrence. In this study, by detecting genomic chromosomal abnormalities in plasma and tumor tissues of patients before and after surgery, the investigators hope to construct a preoperative MVI prediction model and a postoperative MRD monitoring model, so as to provide reference for the precise treatment of HCC.
MVI and MRD confirmed by postoperative pathology are important prognostic factors for recurrence after liver resection, but current assessment methods have low sensitivity and specificity. cfDNA refers to the partially degraded endogenous DNA in the circulating blood that is free from the extracellular part of the body. When derived from dead and lysed tumor cells, it is called ctDNA, having a high chromosomal instability and relating to the tumor subtype and process. By low coverage whole genome sequencing, cfDNA and ctDNA in plasma were extracted and sequenced and chromosomal instability analysis is realized through UCAD pipeline. Therefore, the investigators can predict the trend of tumor by detecting cfDNA in patients, indicate MVI and MRD, carry out individualized staging of patients, predict recurrence and prognosis, and verify the prediction efficiency through follow-up, so as to establish corresponding prediction models.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Anatomical resection group | Anatomical resection of liver cancer tissue |
| |
| Non-anatomical resection group | Non-anatomical resection of liver cancer tissue |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Liver resection method | Procedure | undergo anatomical or non-anatomical resection of liver cancer |
|
| Measure | Description | Time Frame |
|---|---|---|
| MVI model | Establish a preoperative prediction model of MVI by detecting chromosomal abnormalities in peripheral blood cfDNA | 4 years |
| MRD monitor | Monitor postoperative MRD in postoperative patients and predict the recurrence risk and prognosis by detecting chromosomal abnormalities in peripheral blood cfDNA. | 4 years |
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Inclusion Criteria:
Exclusion Criteria:
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The investigators recruit patients dignosed with hepatocellular carcinoma without severe complications and other cancers. These patients eventually undergo liver resection.
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| Name | Affiliation | Role |
|---|---|---|
| Min Zhang, director | First Affiliated Hospital of Zhejiang University | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The First Affiliated Hospital,College of Medicine,Zhejiang University | Hangzhou | Zhejiang | 310003 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28130846 | Result | Heimbach JK, Kulik LM, Finn RS, Sirlin CB, Abecassis MM, Roberts LR, Zhu AX, Murad MH, Marrero JA. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology. 2018 Jan;67(1):358-380. doi: 10.1002/hep.29086. No abstract available. | |
| 29628281 | Result | European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol. 2018 Jul;69(1):182-236. doi: 10.1016/j.jhep.2018.03.019. Epub 2018 Apr 5. No abstract available. |
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| ID | Term |
|---|---|
| D006528 | Carcinoma, Hepatocellular |
| D018365 | Neoplasm, Residual |
| D002869 | Chromosome Aberrations |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
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Blood samples were collected before and after liver resection, and tumor tissues were collected during surgery.
| 12547409 | Result | Imamura H, Matsuyama Y, Tanaka E, Ohkubo T, Hasegawa K, Miyagawa S, Sugawara Y, Minagawa M, Takayama T, Kawasaki S, Makuuchi M. Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy. J Hepatol. 2003 Feb;38(2):200-7. doi: 10.1016/s0168-8278(02)00360-4. |
| 25450201 | Result | Pote N, Cauchy F, Albuquerque M, Voitot H, Belghiti J, Castera L, Puy H, Bedossa P, Paradis V. Performance of PIVKA-II for early hepatocellular carcinoma diagnosis and prediction of microvascular invasion. J Hepatol. 2015 Apr;62(4):848-54. doi: 10.1016/j.jhep.2014.11.005. Epub 2014 Nov 11. |
| 31269959 | Result | Ye Q, Ling S, Zheng S, Xu X. Liquid biopsy in hepatocellular carcinoma: circulating tumor cells and circulating tumor DNA. Mol Cancer. 2019 Jul 3;18(1):114. doi: 10.1186/s12943-019-1043-x. |
| 32279416 | Result | Wang D, Xu Y, Goldstein JB, Ye K, Hu X, Xiao L, Li L, Chang L, Guan Y, Long G, He Q, Yi X, Zhang J, Wang Z, Xia X, Zhou L. Preoperative evaluation of microvascular invasion with circulating tumour DNA in operable hepatocellular carcinoma. Liver Int. 2020 Aug;40(8):1997-2007. doi: 10.1111/liv.14463. Epub 2020 May 23. |
| 40361115 | Derived | Shu Z, Ye T, Wu W, Su M, Wang J, Zhang M, Qian Z, Huang H, Zheng S, Xia Q. Preoperative plasma cell-free DNA chromosomal instability predicts microvascular invasion in hepatocellular carcinoma: a prospective study. BMC Cancer. 2025 May 13;25(1):867. doi: 10.1186/s12885-025-14268-9. |
| D009369 | Neoplasms |
| D008113 | Liver Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D004066 | Digestive System Diseases |
| D008107 | Liver Diseases |
| D009385 | Neoplastic Processes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |