Cancer is fundamentally a disease of molecular change. Long before many cancers produce obvious symptoms, cancer cells may acquire alterations in DNA and RNA that affect how they grow, behave, and interact with surrounding tissues.

For liver cancer—particularly hepatocellular carcinoma (HCC)—researchers are increasingly studying whether these molecular changes can provide useful information about the presence and biology of cancer.

One promising area is blood-based molecular testing, which looks for cancer-associated signals circulating in blood. Rather than relying on a single conventional biomarker, molecular approaches can examine multiple biological signals and evaluate how those signals relate to HCC.

What Does Molecular Testing for Liver Cancer Examine?

Molecular testing can examine different types of biological material, including DNA, RNA, proteins, and other cancer-associated biomarkers.

One area of research relevant to HCC involves fusion genes and fusion transcripts.

Cancer cells can undergo structural changes in their chromosomes. Sometimes these rearrangements join genetic material from two different genes, creating a fusion gene.

When that fusion gene is expressed, the cell can produce an RNA molecule called a fusion transcript.

The distinction is important:

A fusion gene is the underlying DNA-level rearrangement.

A fusion transcript is the RNA product generated from that rearranged gene.

Selected fusion transcripts can be measured in tumor tissue, and research has also demonstrated that some can be detected as circulating cell-free RNA in serum. 

This creates an opportunity to obtain molecular information about cancer from a blood sample.

Fusion Genes Can Provide Information About Tumor Biology

Fusion genes are more than simply laboratory markers. Some can alter cellular signaling and contribute directly to cancer biology.

Research underlying the MoleculeDx scientific program has investigated recurrent fusion events including MAN2A1-FER, PTEN-NOLC1, and SLC45A2-AMACR. Experimental studies have linked selected fusion-related products to signaling pathways involved in cell growth and cancer-associated behavior.

These findings provide a biological foundation for studying fusion genes and their RNA products as cancer-associated molecular signals.

Can Fusion Transcripts Be Detected in Blood?

An important question is whether molecular signals originating from cancer can be detected without directly sampling the tumor.

Research suggests that, for selected fusion transcripts, the answer is yes.

A 2019 HCC serum study reported cancer-associated fusion transcripts in serum samples from patients with hepatocellular carcinoma. The investigators also compared selected serum findings with matched tumor samples, supporting the tumor origin of the circulating signals.

This finding is important because it supports a broader concept:

Blood can carry molecular information associated with changes occurring within a tumor.

Not every HCC contains the same fusion transcripts, however, and individual fusion RNAs can differ in how readily they are detected in circulation.

That is one reason researchers have moved from examining individual fusion transcripts toward multi-marker molecular panels.

Why Measure Multiple Molecular Signals?

Cancer is heterogeneous. Two patients with HCC do not necessarily have exactly the same molecular abnormalities.

A test that depends entirely on one biomarker may therefore miss important biological variation.

A multi-marker approach measures several molecular features and evaluates their combined pattern. Computational models can then integrate those measurements rather than requiring one marker to identify every cancer.

Machine learning is one method for performing this type of multivariable analysis.

In a 2024 HCC serum study involving 136 individuals, researchers evaluated nine serum fusion transcripts and compared different predictive models. One model combining two fusion-transcript measurements with alpha-fetoprotein (AFP) achieved 95% accuracy in the testing and combined study cohorts.

That result demonstrates the potential value of combining biologically different signals. As with any clinical research result, the performance applies to the particular markers, model, specimens, and study population evaluated.

Molecular Testing Provides Different Information From AFP

AFP is a protein biomarker that has long been used in liver cancer evaluation. Fusion-transcript analysis examines something fundamentally different: RNA signals associated with genomic rearrangements in cancer cells.

These different biomarkers therefore provide different biological information.

An HCC that does not produce enough AFP to substantially increase its concentration in blood may still contain other detectable cancer-associated molecular abnormalities.

This is one reason molecular testing is being investigated as an additional source of information in HCC screening and evaluation rather than simply as another version of a conventional protein test.

How MoleculeDx Applies Molecular Research?

The MoleculeDx scientific platform has developed from research into recurrent cancer-associated fusion genes, their biological effects, and the detection of their RNA products in blood.

MoleculeDx applies this research through Fusion-detect™ technology, the molecular platform underlying the Liver Cancer Fusion Predictor.

The approach evaluates multiple cancer-associated fusion-transcript signals rather than depending on one molecular marker. Computational analysis is then used to interpret the measured molecular pattern.

This progression—from understanding fusion-gene biology to detecting circulating fusion transcripts and analyzing multiple signals together—forms the scientific foundation of the MoleculeDx approach.

How Does Molecular Testing Fit With Conventional Liver Cancer Evaluation?

Molecular testing provides an additional type of biological information. It does not eliminate the importance of imaging, medical history, laboratory findings, and clinical evaluation.

A blood-based molecular result should therefore be interpreted in context.

Detection of cancer-associated molecular signals does not, by itself, constitute a pathological diagnosis of HCC. Similarly, failure to detect a particular molecular pattern cannot completely exclude cancer. The original draft appropriately emphasizes the importance of interpreting molecular findings together with other clinical information. 

When findings raise concern for HCC, appropriate clinical evaluation and diagnostic imaging remain important.

Molecular Testing Opens Another Window Into Cancer Biology

Traditional cancer evaluation asks important questions about what can be seen on imaging, what symptoms a patient has, and how conventional laboratory markers have changed.

Molecular testing adds another question:

What biological signals associated with cancer can be detected and measured?

For HCC, research into fusion genes and circulating fusion transcripts demonstrates how blood can provide information about molecular changes associated with cancer.

By examining multiple cancer-associated signals together, blood-based molecular testing may provide information that is not captured by a single conventional biomarker.

That is why molecular testing matters for the future of liver cancer care: it offers another window into the biology of the disease and another source of information that can complement established clinical evaluation.