Downregulation of phosphorylated MKK4 is associated with a poor prognosis in colorectal cancer patients.
Downregulation of phosphorylated MKK4 is associated with a poor prognosis in colorectal cancer patients.
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磷酸化 MKK4 的下调与结直肠癌患者的不良预后相关
DOI：
10.18632/oncotarget.16128
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发表时间：
2017-05-23
期刊：
影响因子：
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通讯作者：
Huang MJ
中科院分区：
文献类型：
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作者：
Wang PN;Huang J;Duan YH;Zhou JM;Huang PZ;Fan XJ;Huang Y;Wang L;Liu HL;Wang JP;Huang MJ
丝裂原活化蛋白激酶激酶4（MKK 4）是Jun N-末端激酶信号传导的关键介质，并影响恶性转移。在这里，我们使用免疫组化来评估磷酸化MMK 4（pMKK 4）水平，并检查其与一组试验性患者样本的临床病理学特征的相关性，这些患者样本包括正常结肠粘膜（NCM）、结直肠腺瘤（CA）和结直肠癌（CRC）组织。还在CRC病例的验证组中评估pMKK 4水平，并伴随随访数据，以确认其临床病理学和预后意义。79.17%的NCM样本中pMKK 4水平较高，33.33%的CA和63.54%的CRC样本中pMKK 4水平下调。pMKK 4下调与转移有关，尤其是转移至肝脏。在验证集中，pMKK 4下调与浸润深度、淋巴结转移、远处转移和TNM分期的增加相关。单因素分析显示pMKK 4评分、肿瘤分化程度和TNM分期与无病生存期和总生存期相关。多因素分析显示pMKK 4表达降低是结直肠癌患者无病生存的独立危险因素。这些结果表明，低pMKK 4免疫化学评分的CRC患者应密切监测，以早期发现可能的复发，特别是肝转移。
Mitogen-activated protein kinase kinase 4 (MKK4) is a key mediator of Jun N-terminal kinase signaling and influences malignant metastasis. Here, we used immunohistochemistry to assess phosphorylated MMK4 (pMKK4) levels and examine their association with the clinicopathological features of a pilot set of patient samples consisting of normal colonic mucosa (NCM), colorectal adenoma (CA), and colorectal cancer (CRC) tissues. pMKK4 levels were also assessed in a validation set of CRC cases with accompanying follow-up data to confirm their clinicopathological and prognostic significance. pMKK4 levels, which were high in 79.17% of NCM samples, were downregulated in 33.33% of CA and 63.54% of CRC samples. pMKK4 downregulation was associated with metastasis, especially to the liver. In the validation set, pMKK4 downregulation was associated with increases in invasive depth, lymph node metastasis, distant metastasis, and TNM stage. Univariate analysis indicated that pMKK4 score, tumor differentiation, and TNM stage were correlated with disease-free survival and overall survival. Multivariate analysis indicated that decreased pMKK4 expression was an independent risk factor for disease-free survival in CRC patients. These results suggest that CRC patients with low pMKK4 immunochemistry scores should be monitored carefully for early detection of possible recurrences, especially liver metastasis.