Hepatocellular Carcinoma (HCC)
Conditions
Keywords
HCC, Liver cancer, tsRNA, Liquid Biopsy, Early Detection
Brief summary
Hepatocellular carcinoma (HCC) is often diagnosed at an advanced stage, and early detection is critical for improving patient outcomes. Despite this, reliable non-invasive biomarkers for early-stage HCC are limited. This study seeks to develop a cell-free tsRNA (cf-tsRNA)-based liquid biopsy assay for accurate detection of early-stage HCC.
Detailed description
Liver cancer is a major global health challenge, ranking as the 5th leading cause of cancer-related deaths in the U.S. and 3rd worldwide, with hepatocellular carcinoma (HCC) accounting for \ 75% of cases. Incidence has more than tripled since 1980, and death rates have risen by \ 2% annually, highlighting the need for improved detection and treatment. Prognosis remains poor: over 50% of HCC cases are diagnosed at stage IV, with a 1-year survival below 30%, whereas early-stage HCC (stages I-II) can achieve up to 74% 5-year survival with curative interventions. Major risk factors include viral hepatitis (HBV, HCV), alcohol abuse, obesity, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD), with non-viral HCC increasing in prevalence, particularly in Western countries. Screening programs target high-risk populations but miss many asymptomatic or average-risk individuals, contributing to late-stage diagnoses. Biomarker discovery holds promise for improving early detection. Alpha-fetoprotein (AFP), the most widely used biomarker, has limited sensitivity for early-stage HCC (39-64%). tsRNAs (tRNA-derived small RNAs) are small, single-stranded RNA molecules derived from mature or precursor tRNAs that were first detected in the urine of patients with cancer in the 1970s. Emerging noninvasive markers offer complementary advantages: cell-free tsRNAs (cf-tsRNAs) are stable and highly sensitive for detection. Integrating these biomarker types could enable robust models for accurate early HCC detection, addressing a critical gap in clinical care. This study seeks to validate a panel of more accurate and non-invasive biomarkers (cf-tsRNAs) in preoperative blood samples. Accurate early detection of HCC would help provide clear criteria for treatment decisions, such as timely surgical intervention or the addition of adjuvant chemotherapy.
Interventions
DIAGNOSTIC_TESTSmall RNA sequence
Comprehensive small RNA sequencing of serum or plasma-derived cf-tsRNAs to identify candidate biomarkers distinguishing HCC from NDC.
DIAGNOSTIC_TESTRt-qPCR
Construction of integrated cf- tsmiRNAs diagnostic classifier using machine learning
Sponsors
City of Hope Medical Center
Study design
Observational model
CASE_CONTROL
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* A histologically confirmed diagnosis of hepatocellular carcinoma. * Received standard diagnostic and staging procedures as per local guidelines * Availability of at least one blood-derived sample, drawn before receiving any curative-intent treatment
Exclusion criteria
• Lack of or inability to provide informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sensitivity | Through study completion, an average of 1 year | True Positive Rate: the probability of a positive test result, conditioned on the individual truly being positive |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Specificity | Through study completion, an average of 1 year | True Negative Rate: the probability of a negative test result, conditioned on the individual truly being negative |
| Proportion of correct predictions (true positives and true negatives) among the total number of cases (i.e.,accuracy) | Through study completion, an average of 1 year | A measure of trueness: proportion of correct predictions (both true positives and true negatives) among the total number of cases examined |
Countries
United States
Contacts
Primary ContactGoel Ajay, PhD
Outcome results
None listed