As the incidence of liver cancer continues to grow - fueled in large part, by rising rates of hepatitis C infections - so too does the need for tests to help diagnose the disease at an earlier stage.
A study appearing in the January 15 issue of Clinical Cancer Research demonstrates that a novel mass-spectrometry based form of proteomic profiling is more accurate than traditional biomarkers in distinguishing liver cancer patients from patients with hepatitis C liver cirrhosis, particularly with regard to identifying patients with small, curable tumors. Led by researchers at Beth Israel Deaconess Medical Center (BIDMC), the study could help lead to earlier diagnostic methods – and subsequent treatments -- for liver cancer.
“Proteomics represents a potentially powerful tool for the serologic recognition of protein profiles associated with cancer,” explains co-senior author Towia Libermann, PhD, Director of the Genomics Center at BIDMC and Associate Professor of Medicine at Harvard Medical School.
“Although this particular proteomics technology, SELDI-TOF MS [surface enhanced laser desorption/ionization time of flight mass spectrometry] had already proven capable of identifying liver cancer in some limited studies, this was the first time that the technology was compared side-by-side with the clinical standard biomarker in a cohort of patients at risk for developing the disease,” adds Liebermann, who is also Director of the Dana-Farber/Harvard Cancer Center Proteomics Core in the Division of Interdisciplinary Medicine and Biotechnology at BIDMC.
Over a single decade, the incidence of liver cancer (hepatocellular carcinoma) increased from 1.8 to 2.5 per 100,000 patients, in large part due to a rise in the spread of hepatitis C virus.
“Hepatitis C has become a tremendous public health problem,” explains co-senior author Nezam Afdhal, MD, Director of the Liver Center at BIDMC and Associate Professor of Medicine at Harvard Medical School. “And a significant number of hepatitis C-infected patients will go on to develop liver cirrhosis.” Cirrhosis results when healthy tissue is replaced by scar tissue, preventing the liver from properly functioning. Cirrhosis itself is responsible for more than 25,000 deaths each year. But, adds Afdhal, secondarily, cirrhosis greatly increases a person's chances of developing liver cancer.
“Each year, cirrhosis patients have a two to five percent chance that their condition will escalate to cancer,” he explains. “And the problem is that, right now, there is no reliable means of detecting liver cancer at an early stage, when surgical treatment is an option. Typically by the time the disease is discovered, the cancer has advanced and treatment options become much more limited.”
The best hope for early detection is cancer biomarkers, serum proteins found in altered amounts in blood or other body fluids. The current biomarker for liver cancer in clinical use is alpha fetoprotein (AFP). In many cases, patients with hepatitis C undergo routine monitoring for AFP levels as an indicator of whether tumors may have developed in their livers.
But, as Libermann explains, the AFP biomarker has a number of shortcomings, including false positives and false negatives. “AFP not only fails to detect many early tumors, but it also lacks specificity. Consequently, elevated AFP levels could be indicators of not only cancer, but also of other liver diseases or even benign conditions, while on the other hand, many patients with small tumors will test negative for AFP.”