CEACAM6 is upregulated by Helicobacter pylori CagA and is a biomarker for early gastric cancer.
CEACAM6 is upregulated by Helicobacter pylori CagA and is a biomarker for early gastric cancer.
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DOI：
10.18632/oncotarget.10528
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发表时间：
2016-08-23
期刊：
影响因子：
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通讯作者：
Jeyasekharan AD
中科院分区：
文献类型：
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作者：
Roy RK;Hoppe MM;Srivastava S;Samanta A;Sharma N;Tan KT;Yang H;Voon DC;Pang B;Teh M;Murata-Kamiya N;Hatakeyama M;Chang YT;Yong WP;Ito Y;Ho KY;Tan P;Soong R;Koeffler PH;Yeoh KG;Jeyasekharan AD
胃癌的早期发现可以挽救生命，但仍然是诊断挑战。在这项研究中，我们的目的是鉴定早期胃癌的细胞表面生物标志物。我们假设由幽门螺杆菌癌蛋白 CagA 诱导的质膜蛋白子集将通过非癌基因成瘾保留在早期胃癌中。使用 CagA 表达诱导系统来鉴定体外差异上调的膜蛋白转录物。然后在基因表达数据集中分析最热门的结果，比较胃癌与正常组织的转录组，以重点关注癌症中保留的标记。在体外 CagA 诱导富集的转录本中，胃癌基因表达数据集中发现 CEACAM6 显着升高。我们使用定量数字免疫组织化学来测量胃癌组织微阵列中的 CEACAM6 蛋白水平。我们证明，与匹配的正常组织相比，早期胃癌中 CEACAM6 有所增加，诊断有效性的 AUC 为 0.83。最后，我们证明荧光偶联的 CEACAM6 抗体与新鲜切除的胃癌异种移植样本紧密结合，并且可以通过内窥镜实时检测。总之，这些结果表明 CEACAM6 上调是对幽门螺杆菌 CagA 的细胞表面反应，并且保留在早期胃癌中。他们强调了胃癌中 CEACAM6 表达与 CagA 之间的新联系，并表明 CEACAM6 是一种有前途的生物标志物，有助于胃早期肿瘤病变的荧光内镜诊断。
Early detection of gastric cancers saves lives, but remains a diagnostic challenge. In this study, we aimed to identify cell-surface biomarkers of early gastric cancer. We hypothesized that a subset of plasma membrane proteins induced by the Helicobacter pylori oncoprotein CagA will be retained in early gastric cancers through non-oncogene addiction. An inducible system for expression of CagA was used to identify differentially upregulated membrane protein transcripts in vitro. The top hits were then analyzed in gene expression datasets comparing transcriptome of gastric cancer with normal tissue, to focus on markers retained in cancer. Among the transcripts enriched upon CagA induction in vitro, a significant elevation of CEACAM6 was noted in gene expression datasets of gastric cancer. We used quantitative digital immunohistochemistry to measure CEACAM6 protein levels in tissue microarrays of gastric cancer. We demonstrate an increase in CEACAM6 in early gastric cancers, when compared to matched normal tissue, with an AUC of 0.83 for diagnostic validity. Finally, we show that a fluorescently conjugated CEACAM6 antibody binds avidly to freshly resected gastric cancer xenograft samples and can be detected by endoscopy in real time. Together, these results suggest that CEACAM6 upregulation is a cell surface response to H. pylori CagA, and is retained in early gastric cancers. They highlight a novel link between CEACAM6 expression and CagA in gastric cancer, and suggest CEACAM6 to be a promising biomarker to aid with the fluorescent endoscopic diagnosis of early neoplastic lesions in the stomach.