Oct 09

LAM’s research collaborators at UCSD prove that non-invasive blood testing may find liver cancer earlier and improve survival – San Diego Union Tribune

Liver cancer can be caught at an early stage through a newly developed blood test, improving the odds for survival, according to a study led by University of California San Diego scientists.

The test looks for changed gene activity, caused by a process called methylation, that indicate liver cancer, said Kang Zhang, M.D., the study’s senior author. Methylation turns genes on or off, but doesn’t affect the underlying DNA sequence.

Early detection is important for the best outcome, Zhang said. Moreover, a blood test is simpler to administer than an invasive liver biopsy or imaging.

Long-term survival is more likely when the cancer is still localized to the liver than when it has spread, according to the National Cancer Institute.

  • People diagnosed with localized liver cancer have a five-year survival rate of 31.1 percent.
  • For those whose cancers have spread to nearby regions, survival drops to 10.7 percent.
  • And for those whose cancers have spread to distant regions, the five-year survival rate is just 2.8 percent.

The study was published Monday in the journal Nature Materials, and can be found at

Zhang was joined by colleagues at UCSD and Chinese institutions, including Sun Yat-sen University Cancer Center in Guangzhou. Results were based on 1,098 hepatocellular carcinoma (liver cancer) patients and 835 healthy control subjects.

Blood tests for liver cancer exist, but they are of comparatively low sensitivity, the study said, often failing to detect those with liver cancer.

In patients with biopsy-confirmed liver cancer, the new blood test achieved an AUC score, a measure of sensitivity and specificity, of 0.969. The most popular existing liver cancer blood test, alpha-fetoprotein, achieved a score of 0.816. A score of 1 represents a perfect test, without false positives or false negatives. A score of 0.5 indicates the test has no ability to detect disease, that is, the score is no greater than chance.

Of the liver cancer patients in the study, 40 percent had a normal level of alpha-fetoprotein, the study stated.

More blood tests for cancers are in the works, said Zhang, founding director of the Institute for Genomic Medicine and co-director of biomaterials and tissue engineering at the Institute of Engineering in Medicine, both at UCSD.

“My lab has been working on all solid tumor cancers,” Zhang said. “Our next targets are lung cancer, breast cancer, colon cancer and prostate cancer. These are the cancers that are causing major deaths worldwide.”

Specifically, the blood test looks for additions to or subtractions from DNA of molecules called methyl groups that control genetic activity. Methylation doesn’t change the underlying DNA sequence, which would be a mutation.

Searching for mutational causes of any particular cancer is difficult, Zhang said, because many different driver mutations could be present in the same type of cancer and the same mutation can cause different cancers.

“However, to become a particular type of cancer, it has to turn on or off certain genes, for example oncogenes or tumor suppressor genes” Zhang said. “One way to turn them on or off is by methylating or demethylating those genes.”

Detecting this “binary” event is much simpler than looking at the vast number of potential mutations, he said.

Liver cancer disproportionately affects Americans of Asian and also Hispanic ancestry. Among Asians, the highest rate occurs among Vietnamese-American men. Among Hispanics, Mexican-Americans in Texas are especially vulnerable.

In many cases, liver cancer is preceded by cirrhosis, and detecting cancer is hard in these patients. With the blood test, liver cancer can not only be detected, but also the prognosis predicted, Zhang said.