An alpha-fetoprotein (AFP) result within the normal range can be reassuring, but it does not necessarily mean that liver cancer is absent.

Some people with hepatocellular carcinoma (HCC), the most common form of primary liver cancer, do not have elevated AFP. For people at increased risk, a normal AFP result must be considered together with clinical history, imaging and other available information.

Researchers are also investigating molecular signals that provide biological information different from AFP. One area of interest is the detection of cancer-associated fusion transcripts in blood.

AFP Is Useful, but It Does Not Tell the Whole Story

AFP is a protein that can be measured in blood. It is used in liver cancer surveillance and evaluation, although not every HCC produces enough AFP to elevate its concentration in blood.

Conversely, elevated AFP is not specific to liver cancer. It can occur in some noncancerous liver conditions and other clinical circumstances. A single AFP measurement cannot establish or rule out an HCC diagnosis.

Why Can HCC Be Present When AFP Is Normal?

HCC is biologically diverse. Tumors can differ in genetic alterations, gene expression and protein production. AFP measures one aspect of this biology—protein expression. A tumor that produces little AFP can still contain other cancer-associated abnormalities.

This distinction provides an opportunity to look beyond conventional protein markers and explore other signals associated with cancer biology.

Looking Beyond AFP to Fusion Transcripts

Chromosomal rearrangements can bring genetic material from two different genes together, creating a fusion gene. When expressed, a fusion gene can produce an RNA molecule called a fusion transcript.

Research from the MoleculeDx scientific program has examined selected fusion transcripts detectable as circulating cell-free RNA in serum from people with HCC.

AFP measures the concentration of a protein in blood. Fusion-transcript analysis investigates selected RNA sequences associated with genomic rearrangements. They are different sources of biological information.

Why Examine Multiple Fusion Transcripts?

Not all HCC tumors have the same molecular alterations. A fusion transcript detectable in one tumor may be absent from another. Multi-marker research therefore evaluates combinations of signals instead of requiring any single marker to detect every cancer.

Computational or machine-learning methods can help evaluate measurements together. The reported performance of any such model applies to the specific study population and assay evaluated, and cannot automatically be generalized to every clinical setting.

How MoleculeDx Applies the Research

The Liver Cancer Fusion Predictor uses Fusion-detect™ technology to examine multiple cancer-associated fusion-transcript signals in blood. The approach builds on published research into serum fusion transcripts and multi-marker analysis of HCC.

A positive molecular result is not by itself a diagnosis of HCC. A negative result also does not completely exclude cancer or replace guideline-directed surveillance.

What Should You Do With a Normal AFP Result?

For people with cirrhosis, chronic hepatitis B or another condition that places them at increased HCC risk, a normal AFP result is not a reason to discontinue appropriate surveillance. Your healthcare professional can recommend a schedule of imaging and other tests based on your risk factors.

A normal AFP level answers one question: AFP is not elevated. It cannot answer every question about whether liver cancer is present.

Research References