來自美國密執(zhí)安州立大學,、賓西法尼亞州立大學，希臘和意大利的大學的研究小組,，利用激光技術從21例卵巢腫瘤和4例正常卵巢組織樣本分離出血管細胞,，進而確定血管細胞表現(xiàn)的基因。
這項結果鑒別了在癌組織血管中大量存在,，但在正常組織血管中不存在的70多種生物標記,。研究人員繼續(xù)深入研究之前與腫瘤血管無關的12種生物標記。這項研究報告刊載于3月1日的Journal of Clinical Oncology,。
研究作者Ronald Buckanovich博士表示,，這些基因中有一部分在腫瘤血管中高度表現(xiàn)，因此可以成為病人生存的預后因子,。研究人員認為當這些基因高度表現(xiàn)時,，表示腫瘤的血管可以有效地新生，因此更具侵略性,。
這項研究分析了大量的腫瘤血管系統(tǒng)或血管,、剖面的樣本,。盡管這次分離的許多基因都已經顯示與其它類型癌有關，但還是發(fā)現(xiàn)了一些新的生物標記,。
另外,，研究人員也發(fā)現(xiàn)幾種于卵巢腫瘤中表現(xiàn)的生物標記，在正常卵巢或其它健康器官中并未表現(xiàn),。研究人員同時發(fā)現(xiàn)這些生物標記在血管生長的正常生殖組織中不存在,，例如胎盤或子宮內膜。因此可以確定這些生物標記具腫瘤之特異性,。
如果這些生物標記確實對卵巢腫瘤具有特異性,，未來將可以發(fā)展出專門破壞腫瘤血管而使腫瘤無法生長的藥物,。
(資料來源 : Bio.com)
部分英文原文：
Journal of Clinical Oncology, Vol 25, No 7 (March 1), 2007: pp. 852-861
© 2007 American Society of Clinical Oncology.
DOI: 10.1200/JCO.2006.08.8583
Tumor Vascular Proteins As Biomarkers in Ovarian Cancer
Ronald J. Buckanovich, Dimitra Sasaroli, Anne O'Brien-Jenkins, Jeffrey Botbyl, Rachel Hammond, Dionysios Katsaros, Raphael Sandaltzopoulos, Lance A. Liotta, Phyllis A. Gimotty, George Coukos
From the Center for Research on Reproduction and Women's Health, Abramson Family Cancer Research Institute, Department of Medicine Division of Hematology-Oncology, and Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA; University of Michigan, Ann Arbor, MI; Center for Applied Proteomics and Molecular Medicine, George Mason University, Fairfax, VA; Department of Obstetrics and Gynecology, University of Turin, Turin, Italy; and Molecular Biology and Genetics Program, Democritus University of Thrace, Komotini, Greece
Address reprint requests to George Coukos, MD, PhD, 1315 BRB II/III, 421 Curie Blvd, Philadelphia, PA, 19104; e-mail: [email protected]
Purpose: This study aimed to identify novel ovarian cancer biomarkers and potential therapeutic targets through molecular analysis of tumor vascular cells.
Methods: Immunohistochemistry-guided laser-capture microdissection and genome-wide transcriptional profiling were used to identify genes that were differentially expressed between vascular cells from human epithelial ovarian cancer and healthy ovaries. Tumor vascular markers (TVMs) were validated through quantitative real-time polymerase chain reaction (qRT-PCR) of immunopurified tumor endothelial cells, in situ hybridization, immunohistochemistry, and Western blot analysis. TVM expression in tumors and noncancerous tissues was assessed by qRT-PCR and was profiled using gene expression data.
Results: We identified a tumor vascular cell profile of ovarian cancer that was distinct from the vascular profile of normal ovary and other tumors. We validated 12 novel ovarian TVMs. These were expressed by immunopurified tumor endothelial cells and localized to tumor vasculature. select TVMs were found to be specifically expressed in ovarian cancer and were absent in all normal tissues tested, including female reproductive tissues with physiologic angiogenesis. Many ovarian TVMs were expressed by a variety of other solid tumors. Finally, overexpression of any one of three ovarian TVMs by vascular cells was associated with decreased disease-free interval (all P < .005).
Conclusion: We have identified for the first time the molecular profile of ovarian tumor vasculature. We demonstrate that TVMs may serve as potential biomarkers and molecular targets for ovarian cancer and a variety of other solid tumors.
Supported by National Institutes of Health (NIH) Grant No. R01 CA098951; National Cancer Institute (NCI) Ovarian Cancer Specialized Program of Research Excellence (SPORE) Grant No. P50-CA083638; US Army Medical Research and Materiel Command Grant No. OC-050314; and the Marcia and Philip Rothblum Foundation. R.J.B. was supported by NIH/National Institute of Child Health and Human Development Grant No. K12-HD43459 and the Ovarian Cancer Research Fund. The laser-capture microdissection facility was supported by a generous grant by the Fannie Rippel Foundation.
R.J.B and D.S. contributed equally to this work.
Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.
