Two new studies demonstrate the promise that proteomics holds for advancing cancer care, particularly efforts to improve cancer prevention. Both studies found potential biomarkers that signal the early presence of two forms of cancer for which preventive efforts have proven especially difficult, ovarian cancer and head and neck squamous cell cancer (HNSCC). In both cases, researchers relied on mass spectrometry - a type of technology that allows molecules to be detected even in minute quantities - to analyze proteins for potential biomarkers.

In a study published in the January 2004 issue of Disease Markers, researchers analyzed the low-molecular-weight portion of plasma serum samples from patients with ovarian cancer. They found biomarkers bound to large circulating carrier proteins that were 100 percent predictive of ovarian cancer. In addition, biomarkers bound to the protein albumin had a distinct pattern from those bound to other carrier proteins, suggesting that albumin could prove to be an important target for future diagnostic research.

The biomarker analysis process used in the study is unique, explained lead author and NCI researcher Dr. Arpita I. Mehta, because it focuses on an abundant target, unadulterated large proteins. In the search for biomarkers, carrier proteins like albumin, which are found in high abundance in plasma, have typically been separated out of the samples to be analyzed, he explained. But with the method used in the study, he added, "We can examine what is stuck to these large proteins when we look for cancer biomarkers, instead of throwing them out from the beginning." This is significant, the researchers found in the study, because carrier proteins act "as a reservoir to accumulate the biomarker over time," increasing the biomarker concentration to such an extent where even conventional diagnostic tests can detect their presence.

"We no longer are searching for a single protein that may be diagnostic for cancer, but rather a host or combination of protein markers that could be much more accurate," noted Dr. Lance Liotta, co-director of the NCI-Food and Drug Administration Clinical Proteomics Program.

The program's other co-director, Dr. Emanuel Petricoin, agreed that the finding is an important advance. "Based on this discovery, investigators could uncover thousands of biomarkers never before known to exist in the blood," he said.

In related news, in an NCI-funded study published in the January 2004 issue of the Archives of Otolaryngology, researchers from Eastern Virginia Medical School and Penn State College of Medicine used the same form of mass spectrometry employed in the ovarian cancer study - known as SELDI - to search for HNSCC biomarkers. HNSCC represents 5 percent of all U.S. cancers. The researchers screened blood serum samples from 99 patients with HNSCC, 25 "healthy" smokers (smoking is a well-established risk factor for HNSCC), and 102 healthy controls. Several biomarkers were found that were present more commonly in patients with HNSCC than in healthy smokers or control patients. The team then developed a classification system based on the biomarkers that could distinguish between patients with HNSCC and the two other subject groups with 80 to 92 percent accuracy. The presence of known HNSCC tumor markers could also be detected using this analytical technique.

"SELDI protein fingerprinting represents a paradigm shift from traditional cancer diagnostic approaches," the researchers concluded, and "may allow for the development of a reliable screening test for the early detection and diagnosis of HNSCC, as well as the potential identification of tumor biomarkers."