黏蛋白4及胰岛素样生长因子-2对ⅢA-N2期非小细胞肺癌预后的影响

Effects of mucin 4 and insulin-like growth factor-2 on prognosis of N2 non-small cell lung cancer

目的观察黏蛋白4（MUC4）及胰岛素样生长因子-2（IGF-2）在ⅢA-N2期非小细胞肺癌中的表达，探讨其对ⅢA-N2期肺癌患者预后的影响。方法收集96例ⅢA-N2期肺癌患者的石蜡标本构建组织芯片，采用免疫组织化学方法检测MUC4、IGF-2在ⅢA-N2期肺癌中的表达，并分析MUC4及IGF-2的表达与临床病理参数、淋巴结转移情况及患者预后的关系。结果全组患者中，MUC4表达率高，为48．9％，在不同的淋巴结转移站数、个数，隆突下淋巴结转移，区域淋巴结转移及临床（病理）N2的癌组织中，表达差异有统计学意义（P〈0．05）；MUC4高表达患者其中位生存期达到43个月，5年生存率为32．6％，明显优于低表达患者（P〈0．01），而IGF-2高表达患者中位生存期为19个月，5年生存率仅为15．1％，明显低于低表达组（P〈0．001），在COX多因素分析中，MUC4及IGF-2的表达水平均是影响ⅢA-N2期肺癌患者预后的独立因素（P〈0．01），且MUC4与IGF-2的表达呈负相关（r=-0．226，P〈0．05）。联合MUC4及IGF-2将全组患者行进一步亚组分析，其中MUCA＋＋IGF-2-组的预后最好，其5年生存率高达49．7％，均优于其他3组（P〈0．01）。结论MUCA及IGF-2可作为影响ⅢA-N2期非小细胞肺癌预后的分子标志物，联合MUCA及IGF-2可将N2期非小细胞肺癌分为不同的亚组，其中MUCA＋＋IGF．2-组的预后最好，可行积极的以手术为主的综合治疗。

Objective We used prognosis-related genes of non-small cell lung cancer （NSCLC） to re-stage the N2 stage NSCLC and further guided the individualized treatment of N2 lung cancer that can he proposed for different therapeutic strategies. Methods We collect 96 patients with N2 lung cancer paraffin specimens, using two-step EnVision immunohistochemical to detect the expression of mucin 4 （MUCA） and insulin-like growth factor-2 （IGF-2） in these tissues. We analysis the correlation between the expression of MUC4 and IGF-2 and elinieopathologieal parameters, lymph node metastasis, prognosis. Results In different clinical and pathological parameters, MUCA expression did not reached significant difference in different gender, age, smoking status, tumor location, general location, pathology, tumor size and T stage of lung cancer. For mediastinal lymph node metastasis, MUCA in different lymph node sta- tions, number of lymph node metastasis, subearinal lymph node metastasis, regional lymph node metastasis and clinical （pathological） N2 of the cancer, showed differential expression （P 〈0. 05 ） ; In high expres- sion of MUC4 group, the median DFS was 35 months and 5 years disease-free survival rate reached 25.3 % , far better than the low expression group（ P 〈 0. 01 ）. The high expression of IGF-2 total of 53 patients, median survival period was 19 months, and 5-year survival rate only 15.1% , significantly lower than the low expression group （ P 〈 0. 01 ）. Spearman rank correlation analysis showed that ： in N2 lung cancer tissues, MUC4 and IGF-2 expression was negatively correlated （ r = - 0. 226, P 〈 0. 05 ）. Com- bined with MUCA and IGF-2 on the ⅢA-N2 lung cancer molecular staging, in which MUCA ＋ ＋ IGF-2- group, the best prognosis, with 5-year survival rate was 49.7 % （ P 〈 0. 01 ）. Conclusion United MUCA and IGF-2 is divided N2 non-small cell lung cancer into different subgroups. MUC4 ＋ ＋ IGF-2 - group have the best prognosis, and completely resection is the better choice for them. For the subgroups with poorprognosis, resection is not advocated, but the choice of chemoradiotherapy is much better.