pERK和MMP-9在非小细胞肺癌中的表达及临床意义

Expression of pERK and MMP-9 in Non-small Cell Lung Cancer and The Clinic Significance

目的：研究磷酸化细胞外信号调节激酶（pERK）和基质金属蛋白酶9（MMP-9）在非小细胞肺癌（NSCLC）中的表达及临床意义。方法：应用免疫组织化学法检测唐山市协和医院、唐山市人民医院1999年1月-2002年12月手术切除的160例NSCLC及20例正常肺组织pERK与MMP-9蛋白的表达，并分析其与临床病理参数的相关性。结果：pERK在NSCLC和正常肺组织阳性率分别为61.3％（98／160）和0（P〈0．05）。NSCLC高、中、低分化组阳性率分别为49．1％（27／55）、54．3％（19／35）、74．3％（52／70），低分化组阳性率高于中、高分化组（P=-0．039，P=-0．004）。Ⅰ～Ⅱ期阳性率为49．5％（45，91），Ⅲ～Ⅳ期阳性率为76．8％（53，69），P=0．000；有淋巴结转移组阳性率为80．6％（58／72），无淋巴结转移组为45．5％（40／88）。P=0．000；pERK阳性组1、3、5年生存率分别为74．5％、42．9％、19．4％，pERK阴性组分别为82．3％、56．5％、37．1％（P=0．002）。MMP-9在NSCLC和正常肺组织阳性率分别为65．0％（104／160）和15．0％（3／20），P〈0．05。NSCLC高、中、低分化组阳性率分别为54．5％（30／55）、51．4％（18／35）、80．0％（56／70），低分化组阳性率高于中、高分化组（P=0．002，P=0．002）；Ⅰ～Ⅱ期阳性率为53．8％（49／91），Ⅲ～Ⅳ期阳性率为79．7％（55／69），P=0．001；有淋巴结转移组阳性率为80．6％（58/72）．无淋巴结转移组为52．3％（46／88），P=0．000。MMP-9阳性组1、3、5年生存率分别为72．1％、37．5％、18.3％．MMP-9阴性组1、3、5年生存率分别为87．5％、67．9％、41．1％（P=0．002）。pERK与MMP-9在非小细胞肺癌中呈正相关（r=0．438，P=0．000）。结论：pERK和MMP-9在NSCLC中高表达，pERK可能部分通过正调节MMP-9促进NSCLC侵袭和进展，pERK和MMP-9过表达预示NSCLC预后不良。

Objective： To investigate the expression of pERK and MMP-9 in non-small cell lung cancer （NSCLC） and its clinical significance. Methods： The expression of pERK and MMP-9 protein was assessed with immunohis-tochemistry in lung tissues from 160 patients with NSCLC collected from October 1999 to December 2002 and 20 samples of normal lung tissue. We analyzed the correlation of the expression of pERK and MMP-9 in NSCLC with clinicopathologic parameters. Results： Normal bronchial and alveolar epithelium were negative for pERK expression. The expression rate of pERK in NSCLC samples was 61.3%, significantly higher than that in normal lung tissues （P〈0.05）. The expression of pERK was higher in poorly differentiated NSCLC tissues （74.3%） than in well-differentiated （49.1%） and moderately differentiated （54.3%） tumor tissues （P= 0.039 and P=0.004）. The expression of pERK was much higher in patients with lymph node metastasis （80.6%：45.5%） （P=-0.000）. The expression of pERK was also higher in stage Ⅲ and Ⅳ than in stage Ⅰ and Ⅱ （76.8%：49.5%） （P=0.000）. The overall 1-, 3-, and 5-year survival rates of patients with pERK expression （74.5%, 42.9%, and 19.4%, respectively） were lower than those without pERK expression （82.3%, 56.5%, and 37.1%, respectively） （P=0.002）. The expression rates of MMP-9 in normal bronchial and alveolar epithelium in NSCLC samples were 15% and 65.0%, respectively （P〈0.05）. The expression of MMP-9 was higher in poorly differentiated NSCLC tissues （80.0%） than in well-differentiated and moderately differentiated NSCLC tissues （54.5% and 51.4%, respectively） （P=0.002 and P=0.002）. The expression of MMP-9 was much higher in patients with lymph node metastasis （80.6%：52.3%） （P=0.000）. The expression of MMP-9 was also higher in stage Ⅲ and Ⅳ tissues than in stage Ⅰ and Ⅱ tissues （79.7%：53.8%） （P=0.001）. The overall 1-, 3-, and 5-year survival rates in patients with MMP-9 expression （72.1%, 37.5%, and 18.3%） were lower than in patients without MMP-9 expression （87.5%, 67.9%, and 41.1%） （P=0.002）. There was a positive correlation between pERK expression and MMP-9 expression, with a Pearson correlation value of 0.438. Conclusion： Compared with normal lung tissues, tissues from NSCLC show an upregulation of pERK and MMP-9, and the expression of these 2 genes enhances tumor progression. Overexpression of pERK and MMP-9 is significantly correlated with poor prognosis in patients with NSCLC.