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Abstract：
OBJECTIVE: To investigate the expression of Nanog and its regulatory relationship with MMP-2/MMP-9 proteins in esophageal squamous cell carcinoma (ESCC).
METHODS: We detected Nanog and MMP-2/MMP-9 protein expressions in 127 ESCC tissues and 82 adjacent normal tissues using immunohistochemistry and explored their correlations with the clinicopathological parameters and prognosis of the patients. GEO database was utilized to analyze the pathways enriched with the stemness-related molecules including Nanog, and TIMER online tool was used to analyze the correlations among TβR1, MMP-2, and MMP-9 in esophageal cancer.
RESULTS: Nanog and MMP-2/MMP-9 proteins were significantly upregulated in ESCC tissues and positively intercorrelated. Their expression levels were closely correlated with infiltration depth and lymph node metastasis of ESCC but not with age, gender, or tumor differentiation. The patients with high expressions of Nanog and MMP-2/MMP-9 had significantly shorter survival time. Bioinformatics analysis showed enrichment of stemness-associated molecules in the TGF-β signaling pathway, and the expressions of MMP-2/MMP-9 and TβR1 were positively correlated. In cultured ESCC cells, Nanog knockdown significantly decreased the expression of TβR1, p-Smad2/3, MMP-2, and MMP-9 and strongly inhibited cell migration.
CONCLUSIONS: The high expressions of Nanog, MMP-2, and MMP-9, which are positively correlated, are closely related with invasion depth, lymph node metastasis, and prognosis of ESCC. Nanog regulates the expressions of MMP-2/MMP-9 proteins through the TGF-β signaling pathway, and its high expression promotes migration of ESCC cells.
METHODS: We detected Nanog and MMP-2/MMP-9 protein expressions in 127 ESCC tissues and 82 adjacent normal tissues using immunohistochemistry and explored their correlations with the clinicopathological parameters and prognosis of the patients. GEO database was utilized to analyze the pathways enriched with the stemness-related molecules including Nanog, and TIMER online tool was used to analyze the correlations among TβR1, MMP-2, and MMP-9 in esophageal cancer.
RESULTS: Nanog and MMP-2/MMP-9 proteins were significantly upregulated in ESCC tissues and positively intercorrelated. Their expression levels were closely correlated with infiltration depth and lymph node metastasis of ESCC but not with age, gender, or tumor differentiation. The patients with high expressions of Nanog and MMP-2/MMP-9 had significantly shorter survival time. Bioinformatics analysis showed enrichment of stemness-associated molecules in the TGF-β signaling pathway, and the expressions of MMP-2/MMP-9 and TβR1 were positively correlated. In cultured ESCC cells, Nanog knockdown significantly decreased the expression of TβR1, p-Smad2/3, MMP-2, and MMP-9 and strongly inhibited cell migration.
CONCLUSIONS: The high expressions of Nanog, MMP-2, and MMP-9, which are positively correlated, are closely related with invasion depth, lymph node metastasis, and prognosis of ESCC. Nanog regulates the expressions of MMP-2/MMP-9 proteins through the TGF-β signaling pathway, and its high expression promotes migration of ESCC cells.
摘要：
目的：探讨Nanog在食管鳞癌中的表达及其与MMP-2/MMP-9蛋白的关系。
方法：采用免疫组织化学方法检测127例ESCC组织和82例癌旁正常组织中Nanog和MMP-2/MMP-9蛋白的表达，并探讨其与患者临床病理参数和预后的关系。GEO数据库用于分析富含干性相关分子的途径，包括Nanog，并利用TIMER在线工具分析TβR1、MMP-2和MMP-9在食管癌中的相关性。
结果：Nanog和MMP-2/MMP-9蛋白在ESCC组织中显著上调且呈正相关。它们的表达水平与ESCC的浸润深度和淋巴结转移密切相关，而与年龄无关。性别,或肿瘤分化。Nanog和MMP-2/MMP-9高表达患者的生存时间明显缩短。生物信息学分析显示TGF-β信号通路中的干性相关分子富集,MMP-2/MMP-9与TβR1的表达呈正相关。在培养的ESCC细胞中，Nanog敲除显著降低TβR1、p-Smad2/3、MMP-2和MMP-9的表达,并强烈抑制细胞迁移。
结论：Nanog的高表达，MMP-2和MMP-9呈正相关，与入侵深度密切相关，淋巴结转移,和ESCC的预后。Nanog通过TGF-β信号通路调节MMP-2/MMP-9蛋白的表达,高表达促进ESCC细胞的迁移。
方法：采用免疫组织化学方法检测127例ESCC组织和82例癌旁正常组织中Nanog和MMP-2/MMP-9蛋白的表达，并探讨其与患者临床病理参数和预后的关系。GEO数据库用于分析富含干性相关分子的途径，包括Nanog，并利用TIMER在线工具分析TβR1、MMP-2和MMP-9在食管癌中的相关性。
结果：Nanog和MMP-2/MMP-9蛋白在ESCC组织中显著上调且呈正相关。它们的表达水平与ESCC的浸润深度和淋巴结转移密切相关，而与年龄无关。性别,或肿瘤分化。Nanog和MMP-2/MMP-9高表达患者的生存时间明显缩短。生物信息学分析显示TGF-β信号通路中的干性相关分子富集,MMP-2/MMP-9与TβR1的表达呈正相关。在培养的ESCC细胞中，Nanog敲除显著降低TβR1、p-Smad2/3、MMP-2和MMP-9的表达,并强烈抑制细胞迁移。
结论：Nanog的高表达，MMP-2和MMP-9呈正相关，与入侵深度密切相关，淋巴结转移,和ESCC的预后。Nanog通过TGF-β信号通路调节MMP-2/MMP-9蛋白的表达,高表达促进ESCC细胞的迁移。
