Ho Melissa E, Quek Sue-Ing, True Lawrence D, Seiler Roland, Fleischmann Achim, Bagryanova Lora, Kim Sara R, Chia David, Goodglick Lee, Shimizu Yoshiko, Rosser Charles J, Gao Yuqian, Liu Alvin Y
Department of Urology, Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA.
Present address: University of California San Francisco Medical Center, San Francisco, CA, USA.
Oncotarget. 2016 Mar 29;7(13):15747-56. doi: 10.18632/oncotarget.7400.
Anterior gradient 2 (AGR2) is a cancer-associated secreted protein found predominantly in adenocarcinomas. Given its ubiquity in solid tumors, cancer-secreted AGR2 could be a useful biomarker in urine or blood for early detection. However, normal organs express and might also secrete AGR2, which would impact its utility as a cancer biomarker. Uniform AGR2 expression is found in the normal bladder urothelium. Little AGR2 is secreted by the urothelial cells as no measurable amounts could be detected in urine. The urinary proteomes of healthy people contain no listing for AGR2. Likewise, the blood proteomes of healthy people also contain no significant peptide counts for AGR2 suggesting little urothelial secretion into capillaries of the lamina propria. Expression of AGR2 is lost in urothelial carcinoma, with only 25% of primary tumors observed to retain AGR2 expression in a cohort of lymph node-positive cases. AGR2 is secreted by the urothelial carcinoma cells as urinary AGR2 was measured in the voided urine of 25% of the cases analyzed in a cohort of cancer vs. non-cancer patients. The fraction of AGR2-positive urine samples was consistent with the fraction of urothelial carcinoma that stained positive for AGR2. Since cancer cells secrete AGR2 while normal cells do not, its measurement in body fluids could be used to indicate tumor presence. Furthermore, AGR2 has also been found on the cell surface of cancer cells. Taken together, secretion and cell surface localization of AGR2 are characteristic of cancer, while expression of AGR2 by itself is not.
前梯度2（AGR2）是一种主要在腺癌中发现的与癌症相关的分泌蛋白。鉴于其在实体瘤中普遍存在，癌症分泌的AGR2可能是尿液或血液中用于早期检测的有用生物标志物。然而，正常器官也表达并可能分泌AGR2，这会影响其作为癌症生物标志物的效用。在正常膀胱尿路上皮中发现AGR2表达一致。尿路上皮细胞分泌的AGR2很少，因为在尿液中检测不到可测量的量。健康人的尿液蛋白质组中没有AGR2的记录。同样，健康人的血液蛋白质组中也没有显著数量的AGR2肽段，这表明尿路上皮向固有层毛细血管的分泌很少。AGR2在尿路上皮癌中表达缺失，在一组淋巴结阳性病例中，仅观察到25%的原发性肿瘤保留AGR2表达。AGR2由尿路上皮癌细胞分泌，因为在一组癌症与非癌症患者的分析病例中，25%的患者的晨尿中检测到了尿AGR2。AGR2阳性尿液样本的比例与AGR2染色阳性的尿路上皮癌比例一致。由于癌细胞分泌AGR2而正常细胞不分泌，因此在体液中测量AGR2可用于指示肿瘤的存在。此外，在癌细胞表面也发现了AGR2。综上所述，AGR2的分泌和细胞表面定位是癌症的特征，而AGR2本身的表达则不是。
