Clinic implication of MUC1 O-glycosylation and C1GALT1 in esophagus squamous cell carcinoma
Clinic implication of MUC1 O-glycosylation and C1GALT1 in esophagus squamous cell carcinoma
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DOI：
10.1007/s11427-017-9345-7
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发表时间：
2018-11-01
影响因子：
9.1
通讯作者：
Huang, Lei
中科院分区：
文献类型：
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作者：
Wang, Yuming;Liao, Xiaodong;Huang, Lei
食道鳞状细胞癌(ESCC)是世界上最具侵袭性的恶性肿瘤之一。我们以前的资料表明，癌蛋白MUC1与ESCC的转移和不良预后有关。然而，MUC1在食管鳞癌中的变化仍不清楚。我们利用Oncomine和COSMIC数据库对MUC1基因拷贝数和基因突变进行了分析，发现MUC1在ESCC中高表达，但基因突变很少。对食管癌组织的进一步研究表明，在14对食管癌组织中，有10对的肿瘤组织中MUC1O-糖基化水平高于癌旁组织。此外，我们还证实了MUC1O-糖基化和C1GALT1之间的潜在联系，并通过对38例ESCC和19例癌旁组织的IHC分析进一步支持了这一点。更重要的是，MUC1糖基化和C1GALT1的共同表达与ESCC患者的淋巴结转移和生存期均呈正相关。我们的工作共同表明，C1GALT1与食管鳞癌中O-糖基化的MUC1相关，这不仅提示了C1GALT1和MUC1O-糖基化在ESCC中的诊断意义，而且为靶向C1GALT1和MUC1O-糖基化以抑制患者ESCC细胞转移开辟了新的视角。
Esophagus squamous cell carcinoma (ESCC) is one of the most aggressive malignant tumors in the world. Our previous data demonstrates that oncoprotein MUC1 is related with metastasis and poor outcome of ESCC. However, alteration of MUC1 in ESCC remains unclear. Using ONCOMINE and COSMIC databases, we analyzed MUC1 gene copy numbers and gene mutations and found that MUC1 had high expression level but few gene mutations in ESCC. Further study of ESCC samples indicated that MUC1 O-glycosylation levels were higher in tumor tissues than that in para-carcinoma tissues in 10 of 14 pairs of ESCC samples. Moreover, we verified a potential link between MUC1 O-glycosylation and C1GALT1, which was further supported by IHC analysis on 38 ESCC and 19 para-carcinoma samples. More importantly, co-expression of MUC1 Oglycosylation and C1GALT1 presented positive correlations with both lymph node metastasis and survival time of ESCC patients. Our work collectively indicates that C1GALT1 is associated with O-glycosylated MUC1 in ESCC, not only suggesting a diagnostic significance of C1GALT1 and MUC1 O-glycosylation in ESCC, but also opening novel insights into targeting C1GALT1 and MUC1 O-glycosylation to suppress ESCC cells metastasis in patients.