Liver Cancer Blood Markers

Liver Cancer Blood Markers: What Do They Tell Us?

Blood tests play an important role in evaluating liver health and detecting biological changes associated with liver cancer. However, not all blood tests measure the same thing, and understanding their differences is essential for interpreting results.

Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, can develop without noticeable symptoms. For people at increased risk, regular surveillance may help identify suspicious changes before the disease becomes advanced.

Traditional blood biomarkers, such as alpha-fetoprotein (AFP), have been used for decades. More recently, advances in molecular diagnostics have made it possible to investigate cancer-associated DNA and RNA signals circulating in blood.

These different biomarkers provide distinct types of information about liver health and cancer biology.

What Are Liver Cancer Blood Markers?

A biomarker is a measurable biological substance or signal that provides information about a disease or physiological condition.

Blood tests used in liver cancer evaluation generally fall into three categories:

Liver injury and function markers: Measurements that help assess liver health but are not specific to cancer.
Protein-based cancer biomarkers: Proteins such as AFP, AFP-L3, and des-gamma-carboxyprothrombin (DCP) that may be associated with HCC.
Molecular biomarkers: Cancer-associated DNA or RNA signals, including circulating fusion transcripts.

Each category measures different aspects of liver biology.

AFP: The Traditional Liver Cancer Blood Marker:

Alpha-fetoprotein (AFP) is a protein normally produced at high levels during fetal development. In adults, AFP concentrations are generally low.

AFP levels may become elevated in patients with HCC, making it a commonly used blood biomarker in liver cancer surveillance and evaluation.

However, AFP has important limitations.

Some patients with HCC have normal AFP levels, particularly when tumors do not produce substantial amounts of the protein. Conversely, AFP can be elevated in certain noncancerous liver conditions and other clinical circumstances.

Therefore, a normal AFP result does not exclude liver cancer, and an elevated AFP result does not establish an HCC diagnosis.

This limitation has encouraged research into additional biomarkers that examine different aspects of cancer biology.

What Do Liver Function Tests Tell Us?

Common laboratory tests include alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, albumin, and measurements related to blood clotting.

These tests provide important information about liver injury and function.

For example, ALT and AST may increase when liver cells are injured, while albumin and clotting measurements can provide information about the liver’s ability to produce essential proteins.

However, these measurements are not specific markers of liver cancer.

Abnormal liver function tests may result from hepatitis, cirrhosis, metabolic liver disease, medication effects, or other conditions. Conversely, some patients with HCC may have relatively preserved liver function.

Liver function tests are therefore valuable for evaluating overall liver health but cannot independently determine whether cancer is present.

AFP-L3 and DCP: Additional Protein Biomarkers:

Researchers and clinicians have also investigated additional protein biomarkers associated with HCC.

AFP-L3 is a specific glycosylated fraction of AFP. Measuring this fraction may provide information different from total AFP concentration.

Des-gamma-carboxyprothrombin (DCP), also known as PIVKA-II, is an abnormal form of prothrombin associated with altered protein processing. Elevated DCP concentrations have been observed in some patients with HCC.

AFP-L3 and DCP are used in certain clinical settings and countries, although their roles in routine surveillance vary according to local guidelines and clinical practice.

These biomarkers may provide complementary information, but neither eliminates the need for appropriate imaging and clinical evaluation.

Biomarker	What it measures	Main clinical relevance
AFP	Serum protein concentration	Established HCC biomarker; may remain normal in patients with cancer
AFP-L3	Specific glycosylated fraction of AFP	Additional protein biomarker investigated or used in selected HCC settings
DCP / PIVKA-II	Abnormal prothrombin	Additional HCC-associated protein biomarker
ALT and AST	Enzyme activity associated with liver injury	Assess liver injury, not cancer specifically
Bilirubin, albumin, clotting measures	Aspects of liver processing and synthetic function	Assess liver function and disease severity
Circulating tumor DNA	Cancer-associated DNA alterations in blood	Molecular liquid-biopsy research and selected clinical applications
Circulating fusion transcripts	RNA products associated with gene-fusion events	Emerging molecular approach investigated for HCC detection

The central distinction is that conventional protein biomarkers and molecular biomarkers measure fundamentally different biological information.

Beyond Proteins: Molecular Signals in Blood

Advances in molecular diagnostics have created opportunities to investigate biological signals that conventional protein tests do not measure.

These include circulating tumor DNA, DNA methylation changes, microRNAs, and other forms of cell-free RNA.

One particularly interesting category is fusion transcripts.

Cancer cells can undergo chromosomal rearrangements that join DNA sequences from two different genes, creating fusion genes. When these rearranged genes are expressed, they can produce distinctive RNA molecules called fusion transcripts.

Selected fusion transcripts can enter the circulation and become detectable as cell-free RNA in serum.

Unlike AFP, which measures a protein concentration, fusion-transcript testing examines RNA sequences associated with cancer-related genomic rearrangements.

This distinction provides a scientific rationale for investigating fusion transcripts as additional blood-based cancer markers.

How MoleculeDx Is Investigating Fusion-Transcript Biomarkers?

Research underlying MoleculeDx technology has demonstrated that selected cancer-associated fusion transcripts can be detected in serum from patients with HCC.

A 2019 study published in Oncotarget investigated circulating fusion transcripts in HCC patients and compared selected serum findings with matched tumor tissues. The findings supported the presence of tumor-associated fusion-transcript signals in blood.

Subsequent research published in The American Journal of Pathology in 2024 evaluated multiple serum fusion transcripts and computational models for distinguishing HCC from non-HCC study participants.

These studies established the scientific foundation for Fusion-detect™ technology, the molecular approach underlying the MoleculeDx Liver Cancer Fusion Predictor.

Rather than relying on one marker, the approach analyzes multiple cancer-associated fusion-transcript signals and evaluates their combined molecular pattern.

This strategy is intended to capture biological information that may not be reflected by conventional protein biomarkers alone.

Why Multiple Biomarkers May Be More Informative?

HCC is biologically heterogeneous. Different tumors can contain different genetic alterations and produce different molecular signals.

A single biomarker may therefore provide only part of the biological picture.

For example, a patient with HCC may have a normal AFP concentration while the tumor contains other detectable cancer-associated molecular abnormalities.

Similarly, different fusion transcripts can vary in their frequency among tumors and their detectability in circulation.

Evaluating multiple markers provides an opportunity to examine complementary biological signals rather than depending entirely on one measurement.

Published MoleculeDx research has investigated combinations of serum fusion-transcript measurements using statistical and machine-learning models. These studies provide evidence supporting further development of multi-marker approaches to HCC detection.

Performance findings from individual studies should be interpreted in the context of their specific models, specimens, and patient populations.

Why Imaging Remains Important?

Blood biomarkers provide information about liver function, protein expression, or cancer-associated molecular signals.

Imaging provides different information.

Ultrasound, contrast-enhanced CT, and MRI can help clinicians identify liver lesions, evaluate their characteristics, and determine whether additional diagnostic assessment is necessary.

For patients at increased risk of HCC, guideline-recommended surveillance commonly involves periodic liver imaging, sometimes accompanied by AFP testing.

Molecular blood testing does not eliminate the need for appropriate imaging or clinical evaluation.

Instead, its potential value lies in providing additional biological information that can be interpreted alongside established methods.

What Should You Do With an Abnormal Blood Test?

An abnormal blood marker does not automatically mean that liver cancer is present.

The appropriate response depends on which marker is abnormal, the degree of abnormality, the patient’s underlying liver condition, and other clinical findings.

Patients should discuss abnormal results with their healthcare providers and determine whether repeat laboratory testing, imaging, or specialist evaluation is appropriate.

Similarly, a normal blood-test result does not necessarily mean that someone at increased risk of HCC should discontinue surveillance.

The most informative interpretation comes from considering laboratory results, imaging, individual risk factors, and changes over time together.

Looking Toward More Informative Liver Cancer Blood Testing:

Liver cancer blood testing has evolved from conventional measurements of liver function and protein biomarkers toward increasingly sophisticated molecular analysis.

AFP, AFP-L3, DCP, and liver function tests continue to provide important clinical information, but they do not measure every biological feature associated with HCC.

Molecular biomarkers, including circulating fusion transcripts, offer another way to examine cancer-associated changes in blood.

The MoleculeDx Liver Cancer Fusion Predictor builds on this scientific direction by analyzing multiple fusion-transcript signals associated with HCC.

The goal is not simply to replace one blood marker with another. It is to obtain more informative molecular evidence about cancer biology by examining signals that conventional biomarkers may not capture.

For people at increased risk of liver cancer, understanding these differences can help support informed discussions with healthcare professionals about appropriate surveillance and evaluation.