MTSS1在非小细胞肺癌中的表达及临床意义

摘要

Objective To explore the expression of metastasis suppressor 1 ( MTSS1) in the development and progression of non-small cell lung cancer ( NSCLC) and its clinical significance. Methods The paraffin-embedded tissues from 98 patients with NSCLC were collected from March 2006 to March 2008 in our hospital to construct tissue microarrays. The immunohistochemistry was used to measure the expression of MTSS1 in 98 tissues of NSCLC and paired corresponding normal adjacent tissues. The relationships between the expression of MTSS1 and clinicopathological characteristics ( age, gender, lymph node metastasis, histological type, degree of differentiation and TNM stage) were analyzed. The overall survival of different expression patterns of MTSS1 was followed up. The pcDNA3�1-MTSS1 expression vector ( pcDNA3�1-MTSS1 group) and pcDNA3�1 empty vector ( pcDNA3�1 group) were construc-ted to transfect the A549 cells. Western blotting was used to analyze the protein levels of MTSS1 in both groups. The proliferation and migration of A549 cells were investigated by tetrazolium salt MTT and scratch test. Results The MTSS1 postive-expression rate of cancer tissue was higher than that of adjacent tissue ( 56�1% vs. 100�0%, P<0�05) . The MTSS1 expression was correlated with lymph node metastasis and TNM stage ( P<0�05) , rather than gender, age, degree of differentiation and pathological types. The median over-all survival of MTSS1 positive expressers was 40�9 months, higher than 21�5 months of negative expressers with statistically significant ( P<0�05) . Multivariate analysis showed that MTSS1 was an independent factor affecting the prognosis of patients with NSCLC. There were a higher level of MTSS1 and lower proliferation and migration ratios in pcDNA3�1-MTSS1 group versus pcDNA3�1 group ( P<0�05) . Conclusion MTSS1 was widely lost in the development and progression of NSCLC and overexpression of MTSS1 can rescue the inhibition of cell growth, indicating that MTSS1 might modulate the development and progression of NSCLC.%目的：探讨转移抑制因子1（ MTSS1）在非小细胞肺癌（ NSCLC）发生发展中的作用及临床价值。方法收集本院2006年3月至2008年3月存档的98例NSCLC石蜡标本，构建组织芯片并采用免疫组织化学法检测98例NSCLC组织及对应癌旁组织中MTSS1的表达，分析其与临床病理参数（年龄、性别、淋巴结转移、病理类型、分化程度和TNM分期）的关系；随访不同MTSS1表达者的生存情况；构建pcDNA3�1-MTSS1表达载体（ pcDNA3�1-MTSS1组）和pcDNA3�1空载体（ pcD-NA3�1组）并分别转染肺癌A549细胞，采用Western blotting法检测两组MTSS1的蛋白水平，采用四甲基偶氮唑盐MTT法和划痕试验检测两组细胞的增殖与迁移情况。结果癌组织中MTSS1阳性表达率低于癌旁组织（56�1％ vs．100�0％；P＜0�05）， MTSS1的表达与性别、年龄、分化程度和病理类型均无关，而与淋巴结转移和TNM分期有关（ P＜0�05）；MTSS1阳性表达者的中位总生存期为40�9个月，高于阴性表达者的21�5个月，差异有统计学意义（ P＜0�05）。 Cox多因素分析显示MTSS1表达是影响NSCLC患者预后的独立因素。 pcDNA3�1-MTSS1组的MTSS1蛋白水平高于pcDNA3�1组，且增殖比例和迁移率均低于pcDNA3�1组，差异均有统计学意义（ P＜0�05）。结论 MTSS1缺失表达在NSCLC的发生发展过程中发挥了重要作用，逆转MTSS1的表达有助于肺癌的防治。