Science：血液可能为癌症的生物标记物的来源

　　一项研究说，科学家发现了血液中的针对特定类型癌症的生物标记物的可能来源。检测癌症相关蛋白质的癌症诊断有时候会失败，这是由于蛋白质寿命短或很难检测到。Arie Admon及其同事发现附着在称为人类白细胞抗原（HLA）的免疫分子上的癌症相关蛋白质的肽片段可能成为多发性骨髓瘤和白血病等癌症患者的生物标记的可能来源。人类白细胞抗原（HLA）分子帮助把降解的蛋白质片断从癌细胞的细胞质运送到细胞表面，在那里，HLA-肽络合物可以被免疫细胞探测到。尽管正常的细胞向血液中分泌少量HLA-肽络合物，癌细胞常常分泌更大的量。

　　这组作者使用生物化学方法探测了患者血浆中的数以千计的HLA-肽络合物；其中许多络合物来自癌症相关蛋白质。此外，这组作者发现同一个人在不同的时候收集和分析的血液的HLA-肽络合物谱具有相似性。这组作者说，由于HLA-肽络合物可以迅速从血液中分离出来，如果这些发现在大量患者和健康的对照者的实验中得到验证，这些肽可能作为在临床上有用的癌症标记物的可能来源。

　　推荐英文摘要：

　　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.