Elevated expressions of MMP7, TROP2, and survivin are associated with survival, disease recurrence, and liver metastasis of colon cancer
Elevated expressions of MMP7, TROP2, and survivin are associated with survival, disease recurrence, and liver metastasis of colon cancer
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DOI：
10.1007/s00384-009-0725-z
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发表时间：
2009-08-01
影响因子：
2.8
通讯作者：
Wan, D. S.
中科院分区：
文献类型：
--
作者：
Fang, Y. J.;Lu, Z. H.;Wan, D. S.
结直肠癌是世界上最常见的癌症之一。采用基因芯片技术检测620例结肠癌组织中17种生物标志物[β-连环蛋白、CD44v7、c-myc、细胞周期蛋白D1、雌激素受体β、丝裂原活化蛋白激酶/细胞外信号调节激酶、maspin、基质金属蛋白酶-7(MMP7)、P53、Pin1、过氧化物酶体增殖物激活受体-γ、Survivin、T细胞转录因子4(TCF4)、转化生长因子β受体II、转化生长因子β、TROP2和Wnt]的表达。应用COX比例风险回归模型分析包括死亡时间、复发时间和肝转移时间在内的终生数据，所有标记物在肿瘤组织中的表达水平均显著高于正常结肠组织。Kaplan-Meier分析显示，TROP2、MMP7和Survivin的高表达与生存率下降有关，TCF4和TROP2的高表达与肿瘤复发有关，CD44v7、细胞周期蛋白D1、MMP7、P53、Survivin和TCF4的高表达与肝转移相关。然而，多因素分析的结果仅显示MMP7、Survivin和TROP2的表达是患者生存率降低的显著预测因素，而TROP2和MMP7的表达分别与疾病复发和肝转移显著相关。此外，MMP7和TROP2表达水平升高分别是疾病复发和肝转移的预测因子。
Colorectal cancer is one of the most common cancers worldwide. We tested the hypothesis that differences in the expression of certain molecular markers of colon cancer may account for different clinical outcomes.Tissue microarray technology was used to assay the expression of 17 biological markers [beta-catenin, CD44v7, c-myc, cyclin D1, estrogen receptor beta, mitogen-activated protein kinase/extracellular signal-regulated kinase, maspin, matrix metalloproteinase-7 (MMP7), p53, Pin1, peroxisome proliferators-activated receptor-gamma, survivin, T cell transcription factor 4 (TCF4), transforming growth factor beta receptor II (TGF beta R II), TGF beta, TROP2, and Wnt] by immunohistochemistry in 620 colon cancer patients. The Cox proportional hazards regression model was applied to analyze the lifetime data, including time to death, time to recurrence, and time to liver metastasis.All the markers were present at significantly higher expression levels in tumor specimens than in normal colonic specimens. Kaplan-Meier analysis showed that high expression of TROP2, MMP7, and survivin were related to decreased survival; TCF4 and TROP2 were related to disease recurrence; and CD44v7, cyclin D1, MMP7, p53, survivin, and TCF4 were related to liver metastasis. However, the results of the multivariate analysis only showed that expression of MMP7, survivin, and TROP2 were significant predictors of lower patient survival, while TROP2 and MMP7 were significantly related to disease recurrence and liver metastasis, respectively.We conclude that elevated survivin, MMP7, and TROP2 expression levels are related to decreased survival. In addition, elevated MMP7 and TROP2 expression levels are predictors of disease recurrence and liver metastasis, respectively.