MUC6 expression is a preferable prognostic marker for invasive mucinous adenocarcinoma of the lung
MUC6 expression is a preferable prognostic marker for invasive mucinous adenocarcinoma of the lung
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MUC6 表达是肺侵袭性粘液腺癌的优选预后标志物
DOI：
10.1007/s00418-022-02093-1
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发表时间：
2022
影响因子：
2.3
通讯作者：
Nakayama J
中科院分区：
文献类型：
--
作者：
Yamanoi K;Fujii C;Yuzuriha H;Kumazawa M;Shimoda M;Emoto K;Asamura H;Nakayama J
胃腺粘蛋白由核心蛋白MUC 6组成，其残基被携带α 1，4-连接的N-乙酰氨基葡萄糖（αGlcNAc）的独特O-聚糖高度糖基化。α GlcNAc-糖基化MUC 6蛋白见于正常胃腺和十二指肠腺体。在胃、胰腺和胆管的癌前病变中经常观察到MUC 6阳性肿瘤细胞上的αGlcNAc糖基化降低，并且在这些器官的浸润性癌中观察到MUC 6表达降低。肺癌（LC）是世界范围内最常见的癌症死亡原因。近年来，腺癌亚型已成为LC最常见的组织学亚型，其侵袭性形式之一是侵袭性粘液腺癌（IMA）。目前，LC IMA的预后标志物尚不清楚。在此，我们分析了54例IMA LC中MUC 5AC、MUC 6和αGlcNAc的表达。MUC 5AC阳性表达50例（93%），MUC 6阳性表达38例（70%），αGlcNAc阳性表达19例（35%）。每个表达水平的评分为0 - 3。αGlcNAc表达评分相对于MUC 6显著降低（P< 0.001）。有趣的是，基于对数秩检验，MUC 6阳性病例的无病生存率显著高于MUC 6阴性病例（P= 0.021）。对于体外分析，我们在A549细胞中异位表达MUC 6，所述A549细胞衍生自LC并具有aKRAS突变。表达MUC 6的A549细胞显示出比对照细胞显著更低的增殖、运动性和侵袭性。最后，MUC 6表达细胞中的F-肌动蛋白染色显示，与FSCN转录物水平降低相关的丝状伪足减少或丢失，FSCN转录物编码细胞迁移所必需的肌动蛋白捆绑蛋白fascin 1。我们的结论是MUC 6表达是IMA LC的一个较好的预后生物标志物。
Gastric gland mucin consists of core protein MUC6 with residues heavily glycosylated by uniqueO-glycans carrying α1,4-linkedN-acetylglucosamine (αGlcNAc). αGlcNAc-glycosylated MUC6 protein is seen in normal gastric and duodenal glands. Decreased αGlcNAc glycosylation on MUC6-positive tumor cells is often observed in premalignant lesions of the stomach, pancreas, and bile duct, and decreased MUC6 expression is seen in invasive cancer of these organs. Lung cancer (LC) is the most common cause of cancer death worldwide. Recently, the adenocarcinoma subtype has become the most common histological subtype of LC, and one of its invasive forms is invasive mucinous adenocarcinoma (IMA). Currently, prognostic markers of LC IMA are unknown. Here, we analyzed MUC5AC, MUC6, and αGlcNAc expression in 54 IMA LC cases. MUC5AC was positively expressed in 50 (93%), MUC6 in 38 (70%), and αGlcNAc in 19 (35%). Each expression level was scored from 0 to 3. The αGlcNAc expression score was significantly decreased relative to MUC6 (P< 0.001). Interestingly, disease-free survival was significantly higher in MUC6-positive than MUC6-negative cases based on the log-rank test (P= 0.021). For in vitro analysis, we ectopically expressed MUC6 in A549 cells, derived from LC and harboring aKRASmutation. MUC6-expressing A549 cells showed significantly lower proliferation, motility, and invasiveness than control cells. Finally, F-actin staining in MUC6-expressing cells revealed a decrease or loss of filopodia associated with decreased levels ofFSCNtranscripts, which encodes an actin-bundling protein fascin1 necessary for cell migration. We conclude that MUC6 expression is a preferable prognostic biomarker in IMA LC.