Decreased alpha-1,4-linked N-acetylglucosamine glycosylation in biliary tract cancer progression from biliary intraepithelial neoplasia to invasive adenocarcinoma.
Decreased alpha-1,4-linked N-acetylglucosamine glycosylation in biliary tract cancer progression from biliary intraepithelial neoplasia to invasive adenocarcinoma.
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DOI：
10.1111/cas.14677
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发表时间：
2020-12
期刊：
影响因子：
5.7
通讯作者：
Nakayama J
中科院分区：
文献类型：
--
作者：
Okumura M;Yamanoi K;Uehara T;Nakayama J
由于早期诊断困难，胆道癌（BTC）通常是致命的。因此，BTC 前体的新型生物标志物是必要的。胆道上皮内瘤变 (BilIN) 是 BTC 的主要前体，根据细胞异型性分为低度或高度。在正常胃粘膜中，胃腺粘蛋白特异性 O-聚糖的独特之处在于，MUC6 上附着有 α1,4 连接的 N-乙酰氨基葡萄糖 (αGlcNAc)。此前，我们报道了αGlcNAc作为分化型胃腺癌的肿瘤抑制因子，并且在胃、胰腺和宫颈肿瘤中MUC6上的αGlcNAc糖基化降低发生在癌症及其前期病变中。然而，胆道肿瘤中αGlcNAc和MUC6的表达模式仍不清楚。在这里，我们分析了 51 例 BTC 病例中的 MUC5AC、MUC6 和 αGlcNAc 表达状态，并比较了每种蛋白的表达与从低级别 BilIN 到侵袭性腺癌 (IAC) 的进展情况。 αGlcNAc 阳性和 MUC6 阳性病变的频率随着肿瘤进展而减少。当我们将每种标志物的表达水平与肿瘤进展进行比较时，我们发现 IAC 中的 MUC6 表达评分显着低于低级别或高级别 BilIN 中（分别为 P < 0.001 或 P < 0.01）。然而，无论组织学分级如何，αGlcNAc 表达评分均较低，并且在所有组织学分级中均低于 MUC6（低级别和高级别 BilIN 的 P < 0.001，IAC 的 P < 0.01）。这些结果表明，αGlcNAc 相对于 MUC6 的表达降低标志着 BTC 进展的开始。 MUC6 上的 α-1,4-连接的 N-乙酰氨基葡萄糖糖基化在胆道上皮内瘤变中已经降低。
Biliary tract cancer (BTC) is typically lethal due to the difficulty of early stage diagnosis. Thus, novel biomarkers of BTC precursors are necessary. Biliary intraepithelial neoplasia (BilIN) is a major precursor of BTC and is classified as low or high grade based on cell atypia. In normal gastric mucosa, gastric gland mucin‐specific O‐glycans are unique in having α1,4‐linked N‐acetylglucosamine (αGlcNAc) attached to MUC6. Previously, we reported that αGlcNAc functions as a tumor suppressor of differentiated‐type gastric adenocarcinoma and that decreased αGlcNAc glycosylation on MUC6 in gastric, pancreatic, and uterine cervical neoplasms occurs in cancer as well as in their precursor lesions. However, αGlcNAc and MUC6 expression patterns in biliary tract neoplasms have remained unclear. Here, we analyzed MUC5AC, MUC6, and αGlcNAc expression status in 51 BTC cases and compared the expression of each with progression from low‐grade BilIN to invasive adenocarcinoma (IAC). The frequency of αGlcNAc‐positive and MUC6‐positive lesions decreased with tumor progression. When we compared each marker’s expression level with tumor progression, we found that the MUC6 expression score in IAC was significantly lower than in low‐grade or high‐grade BilIN (P < 0.001 or P < 0.01, respectively). However, the αGlcNAc expression score was low irrespective of histological grade, and also lower than that of MUC6 across all histological grades (P < 0.001 for low‐grade and high‐grade BilIN, and P < 0.01 for IAC). These results suggest that decreased expression of αGlcNAc relative to MUC6 marks the initiation of BTC progression. Alpha‐1,4‐linked N‐acetylglucosamine glycosylation on MUC6 is already decreased in biliary intraepithelial neoplasia.
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影响因子：
5.7
作者：
Shiratsu K;Higuchi K;Nakayama J
通讯作者：
Nakayama J
DOI：
10.1634/theoncologist.2015-0446
发表时间：
2016-05
期刊：
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影响因子：
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