Circulating Tumor Cell Analysis Improves HCC Diagnosis

A RNA-based digital polymerase chain reaction (PCR) method for analyzing circulating tumor cells greatly improves accuracy in diagnosing hepatocellular carcinoma (HCC), according to a report published in PNAS.


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Recently developed technologies have helped isolate circulating tumor cells, which provides a valuable research tool for tracking treatment response. However, the use of microscopy to identify and analyze circulating tumor cells is a time-consuming process. Standard PCR has been used for creating many copies of a specific nucleic acid segment of DNA, but the recent development of digital PCR allows for much more precise measurement of a nucleic acid segment in a circulating tumor cell in much less time.

Researchers from Massachusetts General Hospital Cancer Center developed a digital PCR assay in an attempt to improve detection of cancer cells in the blood of patients with HCC. Using a circulating tumor cell-iChip that was developed at the Massachusetts General Hospital Center for Engineering in Medicine, researchers assayed blood samples from 6 groups of individuals: patients with newly diagnosed HCC, patients receiving treatment who had existing evidence of disease, patients who appeared to be cured after surgical treatment, patients at risk of developing HCC because of other chronic liver diseases, patients with other types of cancer, and healthy volunteers.

Results of the digital assay showed significantly higher levels of HCC-associated RNA transcripts in blood sampled from patients with HCC than from those with other cancers, chronic liver disease, or healthy controls. A circulating tumor cell score based on the RNA transcripts most associated with HCC generated positive results for more than half of those with untreated HCC. Approximately 28% of patients currently being treated had positive scores.

To determine whether circulating tumor cell scoring could improve diagnosis accuracy compared to the common-practice alpha-fetoprotein (AFP) screening, researchers compared both methods using blood samples from 15 newly diagnosed patients. The circulating tumor cell score detected presence of HCC in 4 patients that AFP did not. AFP alone only detected HCC in one patient that the circulating tumor cell score did not. Combined or used alone, the two tests produced positive results in 67% of patients.

Previous studies have shown combining AFP with specific assays improves diagnosis and leads to a 37% drop in mortality in patients with cancer, but authors acknowledge that accessibility of such tests is limited in developing countries, where the risk of HCC is highest.

"Although there are major hurdles to global implementation of CTC-based digital PCR to screen for HCC, we believe they are surmountable," says Mark Kalinich, Massachusetts General Hospital Cancer Center, co-author of the report. "With the blood stabilization techniques currently being developed in Mehmet Toner's lab at the Center for Engineering in Medicine, blood draws from anywhere in the world could be analyzed at central processing facilities, enabling the high throughput required for global screening efforts."