S100A4和MMP9在非小细胞肺癌中的表达及与浸润、转移和预后的关系

Correlations of S100A4 and MMP9 expressions to infiltration, metastasis and prognosis of non-small cell lung cancer

目的观察S100A4和基质金属蛋白酶9(MMP9)在人非小细胞肺癌(NSCLC)中的表达,探讨其与NSCLC的浸润、转移和预后的关系,为NSCLC临床生物学行为、临床诊断及预后判断提供客观指标。方法采用SP免疫组化法检测41例非小细胞肺癌及6例正常肺组织中S100A4和MMP9的表达水平;运用单因素(Log-rank)和多因素(Cox比例风险模型)生存分析比较两者以及临床各因素与患者预后之间的关系。结果S100A4和MMP9在非小细胞肺癌中的阳性表达率显著高于正常肺组织(P<0.05);在肺腺癌中的阳性表达明显高于肺鳞癌(P<0.01)。在TNM分期中,S100A4在Ⅲ+Ⅳ期明显高于Ⅱ期和Ⅰ期(P<0.01),但是Ⅱ期和Ⅰ期间无显著性差异(P>0.05);MMP9在Ⅲ+Ⅳ期的表达明显高于Ⅱ+Ⅰ期(P<0.05)。S100A4和MMP9的表达在有淋巴结转移组明显高于无淋巴结转移组(P<0.01)。随肿瘤体积的增大S100A4的表达率明显升高(P<0.001)。MMP9阳性率随分化程度的降低而升高,两组间差异显著(P<0.05)。相关分析显示:S100A4和MMP9的表达与淋巴结转移、TNM分期和肿瘤的病理类型均有相关关系;而且S100A4的表达与肿瘤大小及MMP9的表达均相关;MMP9表达与病理分级及S100A4的表达相关。单因素生存分析显示:组织学类型、淋巴结转移情况、临床TNM分期及S100A4和MMP9的表达情况均对患者的生存期有显著影响(P<0.001);多因素分析表明:显示临床TNM分期、S100A4及MMP9的表达状态是影响NSCLC患者预后的独立因素(P<0.05)。结论S100A4和MMP9在非小细胞肺癌中的表达上调,而且与NSCLC的临床生物学行为密切相关.S100A4和MMP9的表达状态是NSCLC独立的预后因素,因此,监测S100A4和MMP9的表达对评估NSCLC患者的预后有重要的作用。

Objective To observe the expressions of metastasis-associated protein （S 100A4） and matrix metalloproteinase 9 （MMP9） in human non-small cell lung cancer （NSCLC） and investigate their correlations to the infiltration, metastasis and prognosis of NSCLC. Methods The expressions of S 100A4 and MMP9 were detected in 41 NSCLC specimens and 6 normal lung tissue specimens using immunohistochemistry with SP method. Univariate and multivariate survival analysis were used to analyze the correlations of S 100A4 and MMP9 to the clinicopathological characteristics and progrnosis of NSCLC. Results Compared with normal lung tissues, NSCLC showed significantly increased positivity for S100A4 and MMP9 expression （P〈0.05）; their expression were significantly higher in adenocarcinoma than in squamous cell carcinoma （P〈0.01 ）, and higher in metastatic NSCLC than in that without lymphatic metastasis （P〈0.01 ）, The positive expression rates of S 100A4 and MMP9 were Significantly higher in tumors in TNM stages Ⅲ ＋Ⅳ than in stages Ⅱ＋Ⅰ （P〈0.05）. S100A4 expression was positively correlated to tumor size （P〈0.001）, while MMP9 was inversely correlated to tumor differentiation （P〈0.05）. The expressions of S100A4 and MMP9 were both correlated to lymphatic metastasis, TNM stages and pathological types （P〈0.05）, and they also showed a mutual correlation （P〈0.01 ）. Univariate survival analysis confirmed the effects of histological types, lymphatic metastasis, clinical TNM stages and expressions of S100A4 and MMP9 on the survival time of NSCLC patients （P〈0.001）. Multivariate survival analysis identified clinical TNM stages and expressions of S100A4 and MMP9 as the independent factors affecting the prognosis of NSCLC （P〈0.05）. Conclusions The expressions of S 100A4 and MMP9 are up-regulated in NSCLC and have significant correlations to the clinical and biological behaviors of NSCLC. S 100A4 and MMP9 status are independent prognostic predictors of NSCLC, and detection of their expressions may help evaluate the prognosis of NSCLC.