Division of Gynecologic Oncology, Walter Reed Army Medical Center, 6900 Georgia Avenue, Washington DC 20307, USA.
Gynecol Oncol. 2011 Jun 1;121(3):586-94. doi: 10.1016/j.ygyno.2011.02.031. Epub 2011 Apr 1.
The present study aimed to identify differentially expressed proteins employing a high resolution mass spectrometry (MS)-based proteomic analysis of endometrial cancer cells harvested using laser microdissection.
A differential MS-based proteomic analysis was conducted from discrete epithelial cell populations gathered by laser microdissection from 91 pathologically reviewed stage I endometrial cancer tissue samples (79 endometrioid and 12 serous) and 10 samples of normal endometrium from postmenopausal women. Hierarchical cluster analysis of protein abundance levels derived from a spectral count analysis revealed a number of proteins whose expression levels were common as well as unique to both histologic types. An independent set of endometrial cancer specimens from 394 patients were used to externally validate the differential expression of select proteins.
209 differentially expressed proteins were identified in a comparison of stage I endometrial cancers and normal post-menopausal endometrium controls (Q<0.005). A number of differentially abundant proteins in stage I endometrial cancer were identified and independently validated by western blot and tissue microarray analyses. Multiple proteins identified with elevated abundance in stage I endometrial cancer are functionally associated with inflammation (annexins) and oxidative processes (peroxiredoxins). PRDX1 and ANXA2 were both confirmed as being overexpressed in stage I cancer compared to normal endometrium by independent TMA (Q=0.008 and Q=0.00002 respectively).
These data provide the basis for further investigation of previously unrecognized novel pathways involved in early stage endometrial carcinogenesis and provide possible targets for prevention strategies that are inclusive of both endometrioid and serous histologic subtypes.
本研究旨在通过对激光显微切割采集的子宫内膜癌细胞进行高分辨率质谱（MS）-基于蛋白质组学分析，鉴定差异表达蛋白。
对 91 例经病理回顾的 I 期子宫内膜癌组织样本（79 例子宫内膜样和 12 例浆液性）和 10 例绝经后妇女正常子宫内膜的离散上皮细胞群体进行基于 MS 的差异蛋白质组学分析。对来自光谱计数分析的蛋白质丰度水平的层次聚类分析揭示了许多表达水平既常见又独特于两种组织学类型的蛋白质。一组来自 394 例患者的独立子宫内膜癌标本用于外部验证选择蛋白质的差异表达。
在比较 I 期子宫内膜癌和正常绝经后子宫内膜对照时，鉴定出 209 个差异表达蛋白（Q<0.005）。在 I 期子宫内膜癌中鉴定出许多差异丰富的蛋白质，并通过 Western blot 和组织微阵列分析进行了独立验证。在 I 期子宫内膜癌中鉴定出的多种高丰度蛋白质与炎症（膜联蛋白）和氧化过程（过氧化物还原酶）功能相关。PRDX1 和 ANXA2 通过独立的 TMA 均被证实与正常子宫内膜相比在 I 期癌症中表达过度（Q=0.008 和 Q=0.00002）。
这些数据为进一步研究早期子宫内膜癌发生中涉及的以前未被识别的新途径提供了基础，并为包括子宫内膜样和浆液性组织学亚型在内的预防策略提供了可能的目标。
