Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 14 Medical Drive, Singapore 117599.
J Proteome Res. 2012 Dec 7;11(12):5736-47. doi: 10.1021/pr300555y. Epub 2012 Nov 26.
Despite decreasing incidence and mortality, gastric cancer remains the second leading cause of cancer-related deaths in the world. Successful management of gastric cancer is hampered by lack of highly sensitive and specific biomarkers especially for early cancer detection. Cell surface proteins that are aberrantly expressed between normal and cancer cells are potentially useful for cancer imaging and therapy due to easy accessibility of these targets. Combining two-phase partition and isobaric tags for relative and absolute quantification methods, we compared the relative expression levels of membrane proteins between noncancer and gastric cancer cells. About 33% of the data set was found to be plasma membrane and associated proteins using this approach (compared to only 11% in whole cell analysis), several of which have never been previously implicated in gastric cancer. Upregulation of SLC3A2 in gastric cancer cells was validated by immunoblotting of a panel of 13 gastric cancer cell lines and immunohistochemistry on tissue microarrays comprising 85 matched pairs of normal and tumor tissues. Immunofluorescence and immunohistochemistry both confirmed the plasma membrane localization of SLC3A2 in gastric cancer cells. The data supported the notion that SLC3A2 is a potential biomarker that could be exploited for molecular imaging-based detection of gastric cancer.
尽管胃癌的发病率和死亡率有所下降,但它仍是全球癌症相关死亡的第二大主要原因。由于缺乏高度敏感和特异的生物标志物,特别是用于早期癌症检测的生物标志物,因此成功管理胃癌受到了阻碍。正常细胞和癌细胞之间异常表达的细胞表面蛋白由于这些靶标易于接近,因此对于癌症成像和治疗具有潜在的用途。我们结合两相分区和等压标记相对和绝对定量方法,比较了非癌和胃癌细胞之间膜蛋白的相对表达水平。使用这种方法,约有 33%的数据集中被发现为质膜和相关蛋白(而在全细胞分析中仅为 11%),其中一些蛋白以前从未与胃癌有关。通过对 13 种胃癌细胞系的免疫印迹和包含 85 对正常和肿瘤组织的组织微阵列的免疫组化分析,验证了 SLC3A2 在胃癌细胞中的上调。免疫荧光和免疫组化均证实 SLC3A2 在胃癌细胞中的质膜定位。这些数据支持 SLC3A2 是一种潜在的生物标志物的观点,它可以用于基于分子成像的胃癌检测。