Risk Factors, Prognosis, and Potential Chemoprevention Drugs in Patients With Recurrent Hepatocellular Carcinoma After Curative Surgeries: a Nationwide Retrospective Cohort Study and a Multi-center Prospective Cohort Analysis

Backgrounds: Surgeries are the mainstream of curative therapies for hepatocellular carcinoma (HCC). However, high risk of recurrent HCC after liver surgeries is still the unsolved clinical issue (early recurrence 21% per year; late recurrence 18% per year). Early recurrence mainly result from disseminated HCC; by contrast, late recurrence usually originate from carcinogenic microenvironment. Currently, no large-scale nationwide studies that integrate laboratory date and clinical information was performed to investigate risk factors and prognosis of post-operative recurrent HCC. Besides, owing to economic issue, few companies would initiate pharmacologic studies to investigate chemoprevention agents for HCC. Furthermore, few biomarkers were discovered from Taiwanese HCC cohort to predict post-operative tumor recurrence because of no standardized cooperative platforms to share biological tissue and clinical information. Therefore, we wish to utilize a nationwide retrospective cohort from integrated national health insurance database (NHIRD) and a prospective multi-center clinical cohort study to address aforementioned issues.

Aims:

1. Investigate risk factors and prognosis of post-operative recurrent HCC in Taiwanese cohort
2. Discover chemoprevention targets from generic drugs to reduce risk of post-operative recurrent HCC
3. Determine biomarkers from Taiwanese cohort in prediction of post-operative recurrent HCC

Study subject and methods:

Nationwide retrospective cohort study

1. Establish prediction models for postoperative recurrent HCC by analyzing surgical HCC patients' clinical information and perioperative laboratory date based on the database of a nationwide retrospective cohort organized by the Ministry of Health and Welfare and Health insurance office
2. Discover chemoprevention agents in association with reduced risk of post-operative recurrent HCC using the aforementioned database

Multicenter prospective cohort study:

1. To discover biomarkers in prediction of post-operative recurrent HCC , we will establish a shared platform to prospectively and systemically collect Taiwanese HCC surgical patients' bio-materials and clinical information from China Medical University Hospital, Asian University Hospital, Mackay Hospital, Taichung Veterans General Hospital, E-Da Hospital,...etc.
2. Using the multicenter prospective cohort, we could validate the results from the nationwide retrospective cohort study, and even improve the prediction models by adding biological parameters that are not available in the nationwide retrospective cohort

Hospital biobank based retrospective case-control study Investigate clinical and biological parameters in prediction of tumor recurrence in HCC surgical patients by hospital based biobank and relevant clinical information

Laboratory in-vivo and in-vitro study Investigate causal relationship between prognosis of HCC and selected biomarkers from above studies as well as four universal tumor theragnostic markers (ADAM9, MTHFD2, RRM2, and SLC2A1) and explore treatment effects of corresponding inhibitors

Expected results: For scientists, they may benefit from the shared database of Taiwanese HCC surgical patients for the HCC related researches; for physicians, they could predict risk of post-operative recurrent HCC in Taiwanese HCC patients and use generic drugs as potentially chemopreventive drugs for HCC; for patients, they could benefit from the personalized medical advice to increase the survival; for the authorities, they could design a policy to reduce the risk of post-operative recurrent HCC, and even prolong HCC patients' survival in a cost-effective way by using generic drugs as chemopreventive regimens for HCC.

Eligibility Criteria:
Inclusion Criteria:

* All HCC surgical patients aged more than 20 year-old who sign informed consent for donating remnant tissue or blood after liver surgeries

Exclusion Criteria:

* Pregnant women