Yiing Lin, M.D. Ph.D.
Project Overview:
Hepatocellular carcinoma (HCC) is a cancer which develops in the livers of patients with liver cirrhosis, most commonly stemming from hepatitis C infection, alcohol abuse, or fat accumulation in the liver. The rise in incidence of cirrhosis and in HCC is expected to continue, given the worsening obesity epidemic. Because of disease patterns in the U.S., HCC, indicence of which has doubled in the past decade, almost always develops in patients who first have cirrhosis. It is therefore important to monitor people with cirrhosis over time for this cancer.
HCC detected at early stages can undergo treatments such as liver transplantation, which can result in 70% five-year survival rates with low recurrence compared to survival of less than 12 months when detected at advanced stages. Despite the availability of effective treatments for early-stage HCC, two-thirds of patients are diagnosed at advanced stages. Better methods of monitoring for HCC can have the potential to increase the longevity of patients with cirrhosis.
The currently recommended method of monitoring for HCC in patients with cirrhosis is a liver ultrasound every six months. However, various studies question the effectiveness of this recommendation. A number of issues, such as physician and patient compliance with monitoring recommendations and the difficulties radiologists have accurately identifying HCC in heavily scarred cirrhotic livers, contribute to difficulties in monitoring. An accurate blood test to diagnose the presence of HCC in a patient with cirrhosis could help to overcome several of these barriers, since blood is easily obtained for repeated testing.
We propose to study a method to test the DNA that is released by HCC into the blood stream. In studies of other cancers, this DNA has been found to contain mutations (abnormal DNA changes) that signal the presence of cancer. We plan to extract DNA from the blood of patients with HCC and to use cutting-edge sequencing techniques to identify cancer mutations.
We predict that being able to find certain DNA mutations within the blood stream of patients with cirrhosis can signal whether that patient has developed HCC. We plan to refine this into a “liquid biopsy” technique that would allow HCC to be diagnosed more frequently and at earlier stages. This would allow more effective treatments to be performed and increase the longevity of affected patients.
