Department of Pathology-Tumor Profiling Unit, VU University Medical Center, Amsterdam, The Netherlands.
Gut. 2012 Jun;61(6):855-64. doi: 10.1136/gutjnl-2011-300511. Epub 2011 Sep 2.
Early detection of colon adenomas at high risk of progression and early-stage colorectal cancer (CRC) is an effective approach to reduce CRC death rates. Current screening methods lack specificity as they detect many adenomas that will never progress to CRC. The authors aimed to identify cell surface protein biomarkers with extracellular domains that could be targeted for molecular imaging and discriminate low-risk adenomas and normal colon from high-risk adenomas and CRC.
Cell surface proteins of five CRC cell lines were biotinylated, isolated and analysed by in-depth proteomics using gel electrophoresis and nanoliquid chromatography coupled to tandem mass spectrometry. Differential expression in adenomas and CRCs was based on mRNA expression and verified by immunohistochemical staining of tissue microarrays.
In total, 2609 proteins were identified in the cell surface fractions. Of these, 44 proteins were selected as promising cell surface candidate biomarkers for adenoma-to-carcinoma progression based on the following criteria: protein identification in at least four out of five cell lines, a predicted (trans)membrane location and increased mRNA expression in CRCs compared to adenomas. Increased protein expression in high-risk adenomas and CRCs compared to low-risk adenomas was confirmed by immunohistochemistry for glucose transporter type 1 (gene symbol SLC2A1; p<0.00001) and prion protein (gene symbol PRNP; p<0.005).
This study revealed glucose transporter type 1, prion protein and 42 other cell surface candidate biomarkers for adenoma-to-carcinoma progression that could potentially serve as targets for emerging molecular imaging modalities like optical imaging, ¹⁹F-MRI and positron emission tomography.
早期发现进展风险高的结肠腺瘤和结直肠癌（CRC）早期是降低 CRC 死亡率的有效方法。目前的筛查方法缺乏特异性，因为它们检测到许多不会进展为 CRC 的腺瘤。作者旨在确定具有细胞外结构域的细胞表面蛋白生物标志物，这些标志物可以作为分子成像的靶点，并区分低风险腺瘤和正常结肠与高风险腺瘤和 CRC。
用生物素标记五个 CRC 细胞系的细胞表面蛋白，通过凝胶电泳和纳流液相色谱-串联质谱进行深度蛋白质组学分析，进行分离和分析。腺瘤和 CRC 中的差异表达基于 mRNA 表达，并通过组织微阵列的免疫组织化学染色进行验证。
总共在细胞表面部分鉴定出 2609 种蛋白质。其中，基于以下标准，选择了 44 种蛋白质作为潜在的腺瘤向癌进展的细胞表面候选生物标志物：至少在五个细胞系中的四个中鉴定出蛋白质，预测的（跨）膜位置和与腺瘤相比，CRC 中 mRNA 表达增加。免疫组织化学证实，葡萄糖转运蛋白 1（基因符号 SLC2A1；p<0.00001）和朊病毒蛋白（基因符号 PRNP；p<0.005）在高危腺瘤和 CRC 中的蛋白表达增加。
本研究揭示了葡萄糖转运蛋白 1、朊病毒蛋白和其他 42 种潜在的细胞表面候选生物标志物，它们可能成为光学成像、¹⁹F-MRI 和正电子发射断层扫描等新兴分子成像方式的靶点。
