Lenkinski Robert E, Bloch B Nicolas, Liu Fangbing, Frangioni John V, Perner Sven, Rubin Mark A, Genega Elizabeth M, Rofsky Neil M, Gaston Sandra M
Department of Radiology, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Ave, Boston, MA 02215, USA.
MAGMA. 2008 Nov;21(6):411-21. doi: 10.1007/s10334-008-0133-3. Epub 2008 Aug 28.
Magnetic resonance imaging (MRI) and MR spectroscopy can probe a variety of physiological (e.g. blood vessel permeability) and metabolic characteristics of prostate cancer. However, little is known about the changes in gene expression that underlie the spectral and imaging features observed in prostate cancer. Tumor induced changes in vascular permeability and angiogenesis are thought to contribute to patterns of dynamic contrast enhanced (DCE) MRI images of prostate cancer even though the genetic basis of tumor vasculogenesis is complex and the specific mechanisms underlying these DCEMRI features have not yet been determined.
In order to identify the changes in gene expression that correspond to MRS and DCEMRI patterns in human prostate cancers, we have utilized tissue print micropeel techniques to generate "whole mount" molecular maps of radical prostatectomy specimens that correspond to pre-surgical MRI/MRS studies. These molecular maps include RNA expression profiles from both Affymetrix GeneChip microarrays and quantitative reverse transcriptase PCR (qrt-PCR) analysis, as well as immunohistochemical studies.
Using these methods on patients with prostate cancer, we found robust over-expression of choline kinase a in the majority of primary tumors. We also observed overexpression of neuropeptide Y (NPY), a newly identified angiogenic factor, in a subset of prostate cancers, visualized on DCEMRI.
These studies set the stage for establishing MRI/MRS parameters as validated biomarkers for human prostate cancer.
磁共振成像(MRI)和磁共振波谱能够探测前列腺癌的多种生理特征(如血管通透性)和代谢特征。然而,对于前列腺癌中所观察到的波谱和成像特征背后的基因表达变化,我们知之甚少。肿瘤诱导的血管通透性和血管生成变化被认为与前列腺癌动态对比增强(DCE)MRI图像的模式有关,尽管肿瘤血管生成的遗传基础很复杂,且这些DCE MRI特征的具体机制尚未确定。
为了识别与人类前列腺癌中磁共振波谱(MRS)和DCE MRI模式相对应的基因表达变化,我们利用组织印记微剥离技术,生成了与术前MRI/MRS研究相对应的前列腺癌根治性切除标本的“整装”分子图谱。这些分子图谱包括来自Affymetrix基因芯片微阵列的RNA表达谱、定量逆转录聚合酶链反应(qrt-PCR)分析以及免疫组织化学研究。
在前列腺癌患者中使用这些方法,我们发现大多数原发性肿瘤中胆碱激酶α强烈过表达。我们还在一部分前列腺癌中观察到神经肽Y(NPY)的过表达,NPY是一种新发现的血管生成因子,在DCE MRI上可见。
这些研究为将MRI/MRS参数确立为人类前列腺癌的有效生物标志物奠定了基础。