目的： 检测穿膜丝氨酸蛋白酶4（transmembrane protease serine 4,TMPRSS4）在早期非小细胞肺癌（non-small cell lung cancer，NSCLC）组织、癌旁组织以及正常肺组织中的表达，分析其在NSCLC肿瘤血管形成中的作用及其临床意义。方法： 选取2009年1月至2010年1月在山东大学齐鲁医院胸外科行手术治疗的NSCLC患者87例，应用免疫组化方法检测NSCLC组织、癌旁组织和正常肺组织中TMPRSS4蛋白表达水平，通过计数CD34免疫染色阳性的内皮细胞测定肿瘤组织内微血管密度（microvessel density, MVD）；另取2014年9月至2014年10月在山东大学齐鲁医院胸外科行手术治疗的原发性早期NSCLC患者14例，应用Real-time PCR检测TMPRSS4 mRNA 在NSCLC组织及邻近正常肺组织内的表达。结果： NSCLC组织中TMPRSS4 mRNA 表达水平显著高于邻近正常肺组织（1.826±0.453 vs 0.829±0.366，P<0.05)；NSCLC组织、癌旁组织中TMPRSS4蛋白表达阳性率显著高于正常肺组织（60.9%、30.0% vs 16.7%，均P<0.05)。TMPRSS4蛋白高表达的癌组织中的MVD显著高于TMPRSS4蛋白低表达的癌组织（P<0.05)。T2癌组织中TMPRSS4蛋白表达及MVD均显著高于T1癌组织（P<0.05)。结论： 早期NSCLC组织中TMPRSS4蛋白高表达与高MVD显著相关，并且TMPRSS4蛋白高表达、高MVD与NSCLC浸润深度密切相关，TMPRSS4可能成为早期NSCLC患者抗癌治疗的新靶点。

Objective : To investigate the relationship between TMPRSS4 expression in early-stage non-small cell lung cancer and tumor angiogenesis and assess its clinical significance. Methods: Samples were collected from 87 NSCLC patients who had received surgical treatment in the Department of Thoracic Surgery of Qilu Hospital between January 2009 and January 2010. TMPRSS4 expression in cancerous, adjacent and normal tissues was assessed using immunohistochemical staining. Intratumoral microvessel density (MVD) was measured by counting immunostained CD34 positive endothelial cells. For Real-time PCR analysis, 14 matched pairs of tumor tissues and adjacent noncancerous tissues were collected from pulmonary lobectomy specimens of patients with NSCLC immediately after surgery in our department between September and October of 2014. Results: The level of TMPRSS4 mRNA in NSCLC tissues was significantly higher than that of the adjacent lung tissues（1.826±0.453 vs 0.829±0.366, P<0.05). The positive rates of TMPRSS4 in NSCLC tissues and adjacent tissues were significantly increased when compared with that in normal lung tissues（60.9%, 30.0% vs 167%，P<0.05). NSCLC tissues with high TMPRSS4 expression have significantly higher MVD than that of low TMPRSS4-expressing cancers (P<0.05). TMPRSS4 expression and MVD in cancerous tissues of T2 stage was significantly higher than that of T1 cancers（P<0.05). Conclusion: Increased TMPRSS4 expression is associated with high MVD in early-stage NSCLC tissue, and high TMPRSS4 expression and MVD in cancer tissue are closely related to the tumor infiltration depth. Thus, TMPRSS4 is a potential novel target for the treatment of patients with early NSCLC.

国家自然科学基金资助项目（No.30571844）；山东省科学与技术发展基金资助项目（No.2009GG10002007）；山东省自然科学基金资助项目（No.ZR2009CM090）；吴阶平基金资助项目（No.320.6750.12393）