An advanced form of a commonly used method to measure circulating tumour cells could help diagnose early stage liver cancer. 

The method in question is polymerase chain reaction (PCR) – a technology used in laboratories to amplify short sequences of DNA.

In a new study by a team from the Massachusetts General Hospital Cancer Center, the method was combined with the hospital’s own CTC-iChip technology – a platform for separating out circulating tumour cells (CTCs) from blood samples.

The combination resulted in greatly improved detection of cancer cells in the blood of patients with hepatocellular carcinoma (HCC), the most common form of liver cancer and second highest cause of cancer death worldwide.

Before the team tested their new CTC-iChip, researchers first identified 10 RNA sequences expressed specifically in HCC cells but not in red blood cells. The team then used their platform to analyse blood samples from newly diagnosed HCC patients, patients receiving treatment for their disease, HCC patients in remission, patients at risk of developing HCC, patients with other forms of cancer, and healthy volunteers.

The team found that HCC-associated RNA sequences were much higher in patients with HCC than in those with other forms of cancer, chronic liver disease or health volunteers.

When examining the number of HCC-associated RNA sequences expressed in each patient group, more than half of those with untreated HCC, 28% of patients being treated for HCC, 8% of healthy volunteers, and 3% of those with other liver diseases exhibited 9 of the specific transcripts. Those in remission demonstrated a similar percentage to the health patient group.

To confirm their findings, the team followed-up with a small group of patients. Two patients who hadn’t had any treatment between each test still demonstrated a higher level of transcript expression while two patients who had had their tumours surgically removed demonstrated much lower transcript numbers. The follow up results suggested a longevity to the team’s method suggesting its possible use as a monitoring tool.

“We have developed an assay capable of detecting a single cancer cell within a background of the tens of billions of cells that comprise whole blood,” said Mark Kalinich of the MGH Cancer Center, co-lead author of the study. “These results hold promise for both the early detection of HCC and for the monitoring of treatment over time.”

The new test offers hope to millions of individuals worldwide with HCC, particularly residents of developing countries where infection with hepatitis B virus – a known cause of HCC – affects more than 248 million individuals.

Using a technique that can identify single HCC cells from a blood sample could help diagnose HCC at a very early stage, improving five-year survival rates from around 15% in late stage HCC to around 50-80% in early stage disease.

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