Heterogeneity and Evolution of hepatoceLlular Carcinoma in Post-transplant HCC Recurrence

Translational Study of Molecular-subtype Heterogeneity and Evolution Pattern in Patients With hepatoceLlular Carcinoma Post-transplant Relapse - HELP 2020 Cohort Study

Objective of Study: This study will evaluate the heterogeneity and evolution pathway between primary HCC and tumor relapse after liver transplant.

According to the "Seed-Soil" theory, the primary hypothesis of this study is that HCC patients with different molecular-subtype experience altered different pattern of post-transplant recurrence, thus may have altered postoperative Recurrence-Free Survival (RFS). Because the donors' liver construct different microenvironment for CTC(circulating tumor cells) colonization. The investigators design this translational study to ①explore potential high recurrent risk HCC molecular-subtypes which might benefit from neoadjuvant systematic therapy or early adjuvant systematic therapy;②identify the molecular subtype heterogeneity of primary and recurrent HCC to guide the precision medicine.

40 specimens will be obtained from the primary tumor during liver transplant surgery and biopsy/specimens from intrahepatic tumor or lung metastasis when the patients experience postoperative relapse. The molecular-subtype of HCC will be determined via whole exom sequence(WES), immunohistochemistry(IHC) and RNA-Seq.

Inclusion Criteria:

• Patients must have pathologically or cytologically or by radiological criteria proven hepatocellular carcinoma; known mixed histology (e.g. hepatocellular carcinoma plus cholangiocarcinoma) or fibrolamellar variant is not allowed
• Patients have post-transplant HCC recurrence(cohort 1), Indication for being an candidate in the waiting list for liver transplant according to multidisciplinary board evaluation(cohort 2)
• The time frame between liver transplant and diagnosis of post-transplant HCC recurrence> 6 months
• No prior hepatectomy or systemic therapy or local therapy (TACE etc.)

Exclusion Criteria:

• History of oncological systemic treatment
• early recurrence(<6 months)
• multiple organ transplantation