Evaluation of Proteomic Profiling for Liver Cancer Diagnosis

A novel mass-spectrometry (MS)-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.

As the incidence of liver cancer continues to grow--partly due to rising rates of hepatitis C infections--so too does the need for tests to help diagnose the disease at an earlier stage. Early detection of specific biomarkers, serum proteins found in altered amounts in blood or other body fluids, has been considered the best method of identifying cancer. 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 the AFP biomarker has a number of shortcomings, including false-positives and false-negatives.

A study led by scientists at Beth Israel Deaconess Medical Center (BIDMC; Boston, MA, USA) demonstrated that a novel MS-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. The study, which appeared in the January 15, 2008 issue of the journal Clinical Cancer Research could help lead to earlier diagnosis--and subsequent treatments--for liver cancer.

The authors of the study evaluated the sensitivity and specificity of surface enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF MS) for the detection of liver cancer and compared its effectiveness with AFP. Examining serum samples of 92 patients--including 51 patients with liver cirrhosis and 41 patients with liver cancer, and among the cancer patients, individuals with both large and small (less than 2 cm) tumors--by SELDI-TOF MS, the investigators were able to identify an 11-protein signature that accurately discriminated between the cirrhosis and cancer patients. The resulting diagnostic value--74 % sensitivity and 88 % specificity--compared favorably with the diagnostic accuracy of AFP (73% sensitivity and 71% specificity), as well as with two other biomarkers currently in clinical development for liver cancer, AFP-L3 and PIVKA-IL.

"Most strikingly,” noted co-senior author Towia Libermann, Ph.D., director of the genomics center at BIDMC and associate professor of medicine at Harvard Medical School (Boston, MA, USA; http), "in patients with small tumors (less than 2 cm), where AFP identified only three, and AFP-L3 and PIVKA-II only one each, the 11-protein signature correctly identified seven of eight patients at this early stage of disease. Proteomics represents a potentially powerful tool for the serologic recognition of protein profiles associated with cancer. Although this particular proteomics technology, SELDI-TOF MS, 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.”


Related Links:
Beth Israel Deaconess Medical Center
Harvard Medical School