一項研究說,，科學(xué)家發(fā)現(xiàn)了血液中的針對特定類型癌癥的生物標記物的可能來源,。檢測癌癥相關(guān)蛋白質(zhì)的癌癥診斷有時候會失敗，這是由于蛋白質(zhì)壽命短或很難檢測到,。Arie Admon及其同事發(fā)現(xiàn)附著在稱為人類白細胞抗原（HLA）的免疫分子上的癌癥相關(guān)蛋白質(zhì)的肽片段可能成為多發(fā)性骨髓瘤和白血病等癌癥患者的生物標記的可能來源,。人類白細胞抗原（HLA）分子幫助把降解的蛋白質(zhì)片斷從癌細胞的細胞質(zhì)運送到細胞表面，在那里,，HLA-肽絡(luò)合物可以被免疫細胞探測到,。盡管正常的細胞向血液中分泌少量HLA-肽絡(luò)合物，癌細胞常常分泌更大的量,。
這組作者使用生物化學(xué)方法探測了患者血漿中的數(shù)以千計的HLA-肽絡(luò)合物,；其中許多絡(luò)合物來自癌癥相關(guān)蛋白質(zhì)。此外,，這組作者發(fā)現(xiàn)同一個人在不同的時候收集和分析的血液的HLA-肽絡(luò)合物譜具有相似性,。這組作者說，由于HLA-肽絡(luò)合物可以迅速從血液中分離出來,，如果這些發(fā)現(xiàn)在大量患者和健康的對照者的實驗中得到驗證,，這些肽可能作為在臨床上有用的癌癥標記物的可能來源。（生物谷Bioon.com）
生物谷推薦英文摘要：
PNAS doi:10.1073/pnas.1008501107
Soluble plasma HLA peptidome as a potential source for cancer biomarkers
Michal Bassani-Sternberga, Eilon Barneaa, Ilan Beerb, Irit Avivic, Tami Katzc, and Arie Admona,1
aDepartment of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel;
bIBM Haifa Research Laboratory, Haifa 31905, Israel; and
cBruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa 31096, Israel
The HLA molecules are membrane-bound transporters that carry peptides from the cytoplasm to the cell surface for surveillance by circulating T lymphocytes. Although low levels of soluble HLA molecules (sHLA) are normally released into the blood, many types of tumor cells release larger amounts of these sHLA molecules, presumably to counter immune surveillance by T cells. Here we demonstrate that these sHLA molecules are still bound with their authentic peptide repertoires, similar to those of the membranal HLA molecules (mHLA). Therefore, a single immunoaffinity purification of the plasma sHLA molecules, starting with a few milliliters of patients’ blood, allows for identification of very large sHLA peptidomes by mass spectrometry, forming a foundation for development of a simple and universal blood-based cancer diagnosis. The new methodology was validated using plasma and tumor cells of multiple-myeloma and leukemia patients, plasma of healthy controls, and with cultured cancer cells. The analyses identified thousands of sHLA peptides, including some cancer-related peptides, present among the sHLA peptidomes of the cancer patients. Furthermore, because the HLA peptides are the degradation products of the cellular proteins, this sHLA peptidomics approach opens the way for investigation of the patterns of protein synthesis and degradation within the tumor cells.
