# Integrated analysis of HCC CTCs for Liver Transplant Candidate Selection

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $578,057

## Abstract

PROJECT SUMMARY
Hepatocellular carcinoma (HCC) is the 2nd most common cause of cancer-related deaths worldwide. Liver
transplantation (LT) is the only curative therapy for HCC patients with unresectable, non-metastatic disease who
meet strict radiologic tumor size and number criteria (Milan criteria). Eligible candidates undergo a finite
observation period (>6 months) that allows for an assessment of tumor biology, but which inherently risks HCC
progression and wait-list dropout in 15-20% of patients after 1 year. Despite these selection practices, post-LT
HCC recurrence plagues up to 20% of patients, and is a major cause of allograft loss and patient mortality. There
is a dire need for non-invasive biomarkers capable of dynamic monitoring of tumor biology to better balance the
risk of wait-list dropout and post-LT recurrence, and allowing for improved prioritization of HCC patients to receive
scarce liver allografts. This proposal aims to develop an integrated blood-based analysis (i.e., NanoVelcro
vimCTC Assay for detecting vimentin+ circulating tumor cells [CTCs] and HCC CTC-RNA Assay for HCC-
specific RNA signatures) for wait-listed HCC patients, to identify patients most suitable for LT. The integrated
assay will provide a novel approach to study both phenotypic and molecular characteristics of HCC CTCs.
 Using an HCC-specific multi-marker capture cocktail and optimized immunocytochemistry (ICC) staining
protocol, the proposed NanoVelcro vimCTC Assay is capable of identifying a subpopulation of HCC CTCs with
vimentin expression (named vimCTC, DAPI+/CK+/CD45-/vimentin+). This subpopulation is associated with
increased recurrence in the subset of clinically indistinguishable early-stage patients undergoing curative-intent
treatment. The HCC CTC-RNA Assay was developed by combining CTC isolation with Click Chip, featuring
click chemistry-mediated cell capture and disulfide-cleavage cell release, with downstream RNA expression
profiling of the purified CTCs with NanoString's nCounter platform. This allows for accurate quantification of a
panel of HCC CTC-derived mRNA markers in a non-invasive manner. The resulting vimCTC counts and mRNA
profiles hold great promise to augment the ability of the current LT candidate selection algorithm.
 The proposed research will be implemented via Specific Aim 1a: Conducting a retrospective study in banked
blood samples using NanoVelcro vimCTC Assay to refine the association between vimCTC counts and post-
LT recurrence/wait-list dropout.; Specific Aim 1b: Conducting a prospective study on freshly collected blood
samples to determine association between vimCTC counts and post-LT recurrence/wait-list dropout; and
Specific Aim 2: Conducting a prospective study on freshly collected blood samples to determine the association
between HCC CTC-RNA Assay and post-LT recurrence/wait-list dropout. The central hypothesis evaluated will
be that baseline and longitudinal changes in vimCTCs and aggressive RNA signatures will ...

## Key facts

- **NIH application ID:** 10117212
- **Project number:** 5R01CA246304-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Vatche Agopian
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $578,057
- **Award type:** 5
- **Project period:** 2020-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10117212

## Citation

> US National Institutes of Health, RePORTER application 10117212, Integrated analysis of HCC CTCs for Liver Transplant Candidate Selection (5R01CA246304-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10117212. Licensed CC0.

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