By ecancer reporter Janet Fricker

Blood could provide a potential source of biomarkers for surveillance of certain cancers, suggests a proof of concept study published in the Proceedings of the National Academy of Sciences.

Cancer diagnosis based on the detection of cancer-related proteins in blood sometimes fails because the proteins are short-lived or hard to detect. However, Arie Admon and colleagues from Technion-Israel Institute of Technology (Haifa, Israel) believe that peptide fragments derived from the cancer-related proteins attached to human leukocyte antigens (HLA) could provide a potential source of biomarkers.

The HLA molecules help transport fragments of degraded proteins from the cytoplasm of cells to the cell surface, where HLA peptide complexes are presented for inspection by immune cells. While normal cells secrete small amounts of HLA-peptide complexes in to the blood, cancer cells are thought to secrete higher amounts.

"We postulated that if indeed a significant portion of the plasma soluble HLA (sHLA) molecules are actually released from the diseased cells, and if these molecules carry with them their original peptide cargo, then analysis of the s HLA peptidomes may provide useful information about the tumour cells and an ideal source for disease biomarkers," wrote the authors.

In the current pilot study, peripheral blood and bone marrow samples were taken from patients with multiple myeloma (MM), acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL) and healthy controls. The investigators then used biochemical methods (such as microcapillary chromatography and tandem mass spectrometry) to detect thousands of HLA peptide complexes in the subject's blood.

Results show that when the plasma sHLA peptidomes of the bone marrow and of the peripheral blood samples of MM and ALL patients were compared, up to 89% of the bone marrow derived plasma sHLA peptides were also detected in the plasma sHLA peptidomes of the peripheral blood.

Furthermore, similar sHLA peptidomes were detected in the plasma of the same person collected on different days. "(This) points to reproducibility of the technology, thus raising confidence in its potential usefulness for clinical uses," wrote the authors.

"It can be concluded that the plasma sHLA peptidomics approach described here provides a source of information about the tumour cells within the human body, possibly even as rich in its information content as cancer transcriptomics, proteomics, or metabolomics," wrote the authors.

In future, suggested the authors, healthy individuals could choose to define their normal sHLA peptidomes and then undergo periodic analysis aimed at detecting the telltale changes associated with the onset of diseases.

Article

M Bassani-Sternberg, E Barnea, I Beer et al Soluble plasma HLA peptidome as a potential source for cancer biomarkers PNAS Doi: 10.1073/pnas.1008501107