Clinical promise: earlier HCC detection and response-informed care
MoleculeDx is developing the Liver Cancer Fusion Predictor as a next-generation blood-based screening test for hepatocellular carcinoma (HCC), with a goal of succeeding alpha-fetoprotein (AFP) as the routine blood-biomarker component of HCC surveillance. The technology builds on cancer-associated circulating fusion-transcript research and a proprietary multi-marker model.
The intended clinical value is practical: identify HCC when patients have few or no symptoms, provide more informative blood-based assessment when conventional findings are equivocal, and track changes in tumor-associated molecular signals after treatment. Earlier recognition can enable timely diagnostic work-up and access to potentially curative treatment.
Clinical decision points for HCC care
Four clinical-use scenarios
The Liver Cancer Fusion Predictor is being developed to help clinicians identify HCC earlier, assess indeterminate liver findings, recognize molecular signals when AFP is normal, and evaluate changes in tumor-associated signals after treatment. Each scenario below connects a clinical challenge with information that can guide timely assessment and follow-up.
01Finding HCC earlier
A stronger blood-based screening strategy for high-risk patients
Clinical setting: Patients with cirrhosis, selected chronic hepatitis B risk profiles, or other established HCC surveillance indications.
Why it matters: The goal of the Liver Cancer Fusion Predictor is to take the place of AFP as the blood-based screening test used in routine HCC surveillance, improving recognition of cancer-associated signals before symptoms develop. Earlier HCC identification can expand opportunities for effective treatment.
Clinical decision: A concerning screening result would prompt timely diagnostic assessment, including liver imaging as appropriate. A reassuring result would be documented alongside continued scheduled surveillance.
02Uncertain liver findings
Resolve diagnostic uncertainty around liver lesions
Clinical setting: An imaging abnormality is indeterminate, including observations that do not meet definitive LI-RADS LR-5 criteria.
Why it matters: A molecular blood result can contribute another line of evidence when a lesion cannot be confidently characterized by imaging alone.
Clinical decision: A concerning molecular result may support prioritizing additional multiphasic imaging, multidisciplinary review, or biopsy evaluation where clinically indicated.
03AFP-negative HCC
Investigate liver cancer even when AFP is normal
Clinical setting: A patient has substantial HCC risk or suspicious findings but an AFP level within the reference range.
Why it matters: Some HCC tumors do not produce enough AFP to raise serum levels. Circulating cancer-associated fusion-transcript patterns provide a route to detecting biologic signals that AFP alone can miss.
Clinical decision: A concerning result would strengthen the case for expedited assessment rather than accepting normal AFP as reassurance. Interpret findings with imaging and the complete clinical picture.
04Treatment response
Follow molecular tumor burden after HCC treatment
Clinical setting: Serial evaluation after resection, ablation, locoregional therapy, transplantation, or systemic treatment.
Why it matters: A substantial decline in circulating tumor-associated fusion transcripts is consistent with reduced molecular tumor burden and, in the setting of concordant clinical findings, supports at least a partial treatment-response interpretation. Persistent, rising, or newly emerging signals can raise concern for residual or recurrent disease.
Clinical decision: Establish a pretreatment reference when feasible and assess subsequent molecular trends. A fall supports a favorable response assessment, to be evaluated with imaging; a persistent or rising signal supports earlier reassessment for active disease.
2024 evidence: 25/61 treated HCC patients (41%) had complete disappearance of measured serum fusion-transcript signals after treatment. In a frequently detected transcript, 58/61 patients (95%) showed a decline. Several patients with emerging or persistent patterns subsequently had progression or recurrence.
Evidence supporting these clinical applications: Research findings, cohort-specific performance, and treatment-monitoring observations are detailed in the Scientific Evidence and Clinical Performance section below. The goal is to establish the Liver Cancer Fusion Predictor as a next-generation blood-based HCC screening test that can succeed AFP's current role, while diagnostic decisions continue to use appropriate clinical evaluation and imaging. Primary clinical study →
Who may warrant HCC surveillance?
Established guidelines recommend HCC surveillance for many people with cirrhosis and selected people with chronic hepatitis B, including some without cirrhosis. Surveillance eligibility is determined by individual risk, underlying liver disease and fitness to benefit from subsequent evaluation.
Standard surveillance usually centers on imaging, with AFP used in some recommended regimens. Molecular testing should be interpreted as additional information rather than an alternative to indicated surveillance or diagnostic imaging.
Analytical concept
- Blood is collected in an appropriate laboratory-approved collection tube.
- The specimen is transported under defined pre-analytical conditions and processed in the laboratory.
- Cell-free RNA is extracted and selected fusion-transcript sequences are investigated with molecular techniques.
- A proprietary computational model interprets the relevant measurements.
- The result is reported according to the laboratory's current procedures and interpreted in clinical context.
The assay applies proprietary laboratory and computational methods. For specimen handling and ordering requirements, please use the current laboratory collection instructions.
Studies published in 2019 and 2024 documented circulating fusion-transcript detection in HCC and evaluated their value for cancer identification and treatment follow-up. Below are the reported results, with each figure linked to the cohort and model from which it came.
2019: Circulating serum fusion-transcript detection
In a published Oncotarget study, researchers examined serum from 104 patients with HCC and 14 individuals without malignancy. At least one evaluated fusion transcript was detected in 87 of 104 HCC specimens (83.7%); none of the 14 nonmalignant controls tested positive for the panel. These are observed study detection proportions, not an estimate of clinical specificity in a broad surveillance population with chronic liver disease.
104HCC serum samples
87 / 104HCC samples positive (83.7%)
0 / 14Nonmalignant controls positive
Source: Yu et al., Oncotarget (2019).
2024: Multi-marker model validation
The American Journal of Pathology study analyzed nine serum fusion transcripts from 136 individuals (61 with HCC; 75 with non-HCC conditions). Samples from earlier years formed the training cohort (n=82); later samples formed a testing cohort. The reported testing results for selected research models are summarized below.
Source: Yu et al., American Journal of Pathology (2024), Results and supplemental tables. The AFP-containing analyses involve a smaller subset than the four-fusion-only testing cohort; these are not identically sized head-to-head comparisons. The AFP ≥400 ng/mL threshold was an investigational comparator, not a recommendation for routine surveillance.
Model comparisons shown above describe the published 2024 research cohorts. The complete composition and performance of the current clinical product are not inferred from these research-model results.
Monitoring treatment response: what the molecular trend means
Serial serum measurements can make molecular changes after therapy visible. In the 2024 study of 61 HCC patients with before-and-after treatment specimens, 25 patients (41%) became negative for the evaluated circulating fusion-transcript signals; 58 patients (95%) showed a reduction in one commonly detected transcript. The authors linked these patterns to treatment-associated reductions in tumor load.
Signals decrease markedly
Interpretation: Consistent with a reduction in tumor-associated molecular burden and supportive of treatment effect. Clinical action: Document the response trend and correlate it with treatment history, imaging, and other response measures.
Signals persist or decrease only minimally
Interpretation: Raises concern that a biologically active tumor source may remain. Clinical action: Review whether imaging or further evaluation is warranted rather than assuming complete response.
Signals rise or new signals appear
Interpretation: Can suggest residual, recurrent, or progressive HCC, including a changing tumor population. Clinical action: Promptly reassess with appropriate imaging and specialist review, taking account of assay variability and other clinical findings.
A molecular trend is a useful response signal, not a stand-alone substitute for standard response assessment. The commercial assay's complete marker composition and interpretation rules are proprietary.
What this evidence offers the care team
- Earlier concern: In patients at high risk, a meaningful molecular signal could prompt timely investigation before symptomatic disease.
- Response tracking: Serial changes can provide a blood-based view of cancer-associated biology before and after treatment.
- Individualized follow-up: Persistent or emerging signals can identify patients needing closer clinical assessment, while falling signals support a favorable response interpretation when concordant with other findings.
Scientific basis for a next-generation blood screening test
- 2019 serum fusion-transcript study: Investigated selected fusion transcripts in serum from people with HCC and examined relationships with tumor findings.
- 2024 multi-marker study: Evaluated serum fusion transcripts and computational models in cohorts including individuals with and without HCC.
Fusion transcripts arise from genomic rearrangements and provide distinctive RNA signals associated with tumor biology. Multiple targets and computational interpretation help accommodate the heterogeneity of HCC. This research motivates the development of more informative blood-based HCC screening and longitudinal monitoring strategies.
Suggested clinical interpretation of a screening result
Concerning molecular result: Consider timely diagnostic liver imaging and specialist evaluation based on the patient's risk and existing findings. A blood result raises concern but does not constitute a radiologic or pathologic diagnosis.
Reassuring molecular result: Record the result within the ongoing surveillance plan; pursue additional evaluation if imaging, risk factors, or symptoms remain concerning.
Put the test into your clinical workflow
Patients can initiate an order through the secure MoleculeDx booking portal, where the current standard package is shown at $160. Collection locations, service availability, payment and laboratory shipping arrangements are confirmed during the order process.
Clinicians should verify current collection and reporting procedures before ordering. The separate booking application remains the system of record for patient orders; this recovery website does not receive patient data or process payments.
Selected primary publications
Connect patients with testing information
Review the ordering workflow through the secure MoleculeDx booking portal.
