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.  A study appearing in the January 15, 2008 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.  The study could help lead to earlier diagnostic methods – and subsequent treatments — for liver cancer.  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- Alpha fetoprotein (AFP)- in a cohort of patients at risk for developing the disease.  However, 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.  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 mass spectrometry, the investigators were able to identify an 11-protein signature that accurately discriminated between the cirrhosis and cancer patients.  The resulting diagnostic value – 74 percent sensitivity and 88 percent specificity – compared favorably with the diagnostic accuracy of AFP (73 percent sensitivity and 71 percent specificity) as well as with two other biomarkers currently in clinical development for liver cancer, AFP-L3 and PIVKA-IL. Surprisingly in patients with 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.   Thus biomarkers play a major role in all aspects of personalized medicine, not only in early disease detection, but also in outcome prediction and evaluation of therapeutic responses. This study provides strong evidence that serum contains early detection biomarkers and supports the notion that a combination of multiple biomarkers may prove more effective than individual biomarkers for diagnosis of liver cancer, as well as other cancers.