Expression of ATF6 as a marker of pre-cancerous atypical change in ulcerative colitis-associated colorectal cancer: a potential role in the management of dysplasia.
Expression of ATF6 as a marker of pre-cancerous atypical change in ulcerative colitis-associated colorectal cancer: a potential role in the management of dysplasia.
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DOI：
10.1007/s00535-017-1387-1
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发表时间：
2018-05
影响因子：
6.3
通讯作者：
Kawano T
中科院分区：
文献类型：
--
作者：
Hanaoka M;Ishikawa T;Ishiguro M;Tokura M;Yamauchi S;Kikuchi A;Uetake H;Yasuno M;Kawano T
低级别异型增生(LGD)的诊断在溃疡性结肠炎(UC)的治疗中很重要，但通常很难区分LGD和炎性再生上皮。未折叠蛋白反应(UPR)在炎症性肠病和恶性肿瘤中被激活。我们的目的是找出一个与非UC和UC相关的结直肠癌(CRC)发生有关的UPR相关基因，并探讨该目的基因是否对LGD的诊断有用。利用我们的152个癌基因表达数据库，我们确定激活转录因子6(ATF6)为目的基因。对137例手术切除的大肠癌、95例胃镜下切除的腺瘤和PTIS癌以及51例UC患者(93例无瘤结肠炎、31例异型增生和12例UC相关的结直肠癌)的136例标本进行ATF6免疫组织化学分析。评估ATF6和P53作为LGD标志物的诊断准确性。在所有癌组织中均可检测到ATF6的表达，但在正常结肠黏膜中未见表达，且随着细胞异型性(腺瘤伴中度非典型性；重度非典型性)的增加而升高(P<0.001)，在不典型增生和结直肠癌中的表达高于非肿瘤性结肠炎(P<0.001)。值得注意的是，结肠炎和LGD之间的差异是显著的。与P53-IHC相比，ATF6-IHC对LGD与背景炎性粘膜的鉴别诊断准确率更高(敏感性分别为70.8%和16.7%，特异性分别为78.5%和71.0%)。ATF6在非UC和UC相关的结直肠癌癌前病变中均有表达，可用于区分UC患者的LGD和炎性再生上皮。本文的在线版本(doi：10.1007/s00535-0171387-1)包含补充材料，可供授权用户使用。
Diagnosis of low-grade dysplasia (LGD) is important in the management of ulcerative colitis (UC), but it is often difficult to distinguish LGD from inflammatory regenerative epithelium. The unfolded protein response (UPR) is activated in inflammatory bowel disease and malignancies. We aimed to identify a UPR-related gene that is involved in the development of non-UC and UC-associated colorectal cancer (CRC), and to investigate whether the target gene is useful for the diagnosis of LGD. Using our microarray gene expression database of 152 CRCs, we identified activating transcription factor 6 (ATF6) as a target gene. Immunohistochemistry (IHC) of ATF6 were analyzed in 137 surgically resected CRCs, 95 endoscopically resected adenomas and pTis cancers, and 136 samples from 51 UC patients (93 colitis without neoplasia, 31 dysplasia, and 12 UC-associated CRC). The diagnostic accuracy of ATF6 and p53 as markers of LGD was assessed. ATF6 expression was detectable in all CRCs but not in normal colonic mucosa, was elevated with increase in cellular atypia (adenoma with moderate atypia < severe atypia < pTis CRC, p < 0.001), and higher in dysplasia and CRC than in non-neoplastic colitis (p < 0.001). Notably, the difference between colitis and LGD was significant. Compared to p53-IHC, ATF6-IHC had better diagnostic accuracy for distinguishing LGD from background inflammatory mucosa (sensitivity 70.8 vs. 16.7%, specificity 78.5 vs.71.0%, respectively). ATF6 was expressed in lesions undergoing pre-cancerous atypical change in both non-UC and UC-associated CRC and may be used to distinguish LGD from inflammatory regenerative epithelium in UC patients. The online version of this article (doi:10.1007/s00535-017-1387-1) contains supplementary material, which is available to authorized users.
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DOI：
10.1073/pnas.0813036106
发表时间：
2009-03-03
影响因子：
11.1
作者：
Brandl, Katharina;Rutschmann, Sophie;Beutler, Bruce
通讯作者：
Beutler, Bruce
影响因子：
15.8
作者：
Heazlewood CK;Cook MC;Eri R;Price GR;Tauro SB;Taupin D;Thornton DJ;Png CW;Crockford TL;Cornall RJ;Adams R;Kato M;Nelms KA;Hong NA;Florin TH;Goodnow CC;McGuckin MA
通讯作者：
McGuckin MA
影响因子：
3.2
作者：
Fujii, Shigehiko;Katsumata, Daisuke;Fujimori, Takahiro
通讯作者：
Fujimori, Takahiro
影响因子：
29.4
作者：
Gupta, Roopali Bansal;Harpaz, Noam;Ullman, Thomas
通讯作者：
Ullman, Thomas
影响因子：
8
作者：
Luo, B.;Lee, A. S.
通讯作者：
Lee, A. S.