Digital CTC Assay Improves Liver Cancer Diagnosis

Liver cancer, including hepatocellular carcinoma (HCC), is the second highest cause of cancer death in the world. HCC is particularly prevalent in developing countries, where its incidence is driven by infection with the hepatitis B virus, which now affects more than 248 million individuals.

The use of an advanced form of the commonly used polymerase chain reaction (PCR) method to analyze circulating tumor cells may greatly increase the ability to diagnose early-stage cancer, increasing the likelihood of successful treatment as current blood-based strategies for detecting HCC, such as serum levels of alpha-fetoprotein (AFP), have had poor results.

A large team of scientists working with those at Massachusetts General Hospital Cancer Center developed a digital PCR assay by first identifying 10 specific ribonucleic acid (RNA) transcripts that were expressed in HCC cells but not in blood components. They assayed blood samples from six groups of individuals: newly diagnosed HCC patients; HCC patients receiving treatment who still had evidence of disease; HCC patients who appeared to be cured after surgical treatment, including liver transplantation; patients at risk for developing HCC because of other chronic liver diseases; patients with other types of cancer, including some with liver metastases; and healthy volunteers.

The circulating tumor cells (CTC)-iChip digital PCR analysis revealed significantly higher levels of the HCC-associated RNA transcripts in blood samples from patients with HCC than from those with other cancers, with chronic liver disease or healthy controls. The use of a CTC score based on the nine RNA transcripts most significantly associated with HCC generated positive results for more than half of those with untreated HCC, but only around 8% of healthy controls and 3% of those with other liver diseases. Around 28% of patients currently being treated had positive scores, and the percentage of positive scores among patients with no evidence of disease after treatment was similar to that of healthy controls.

Mark Kalinich, an MD/PhD candidate and co-lead author of the study said, “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. Our test provides highly specific detection of cancer in patients with HCC, compared with healthy individuals and with those at high risk for developing the disease. These results hold promise for both the early detection of HCC and for the monitoring of treatment over time.” The study was published on January 17, 2017, in the Proceedings of the National Academy of Sciences of the United States of America.