Sun Dianshui, Li Xin, Ma Maoqiang, Liu Jie, Xu Ying, Ye Lan, Hou Huaying, Wang Cuihong, Li Xiaomei, Jiang Yuhua
Cancer Center, The Second Hospital of Shandong University, Jinan.
Medical Department, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan.
Jpn J Clin Oncol. 2015 May;45(5):464-73. doi: 10.1093/jjco/hyv009. Epub 2015 Feb 2.
The incidence of brain metastases greatly varies in patients with non-small-cell lung cancer, and molecular markers are considered to predict brain metastases. Therefore, this study sought to identify the predictive value and potential mechanisms of miRNA-328 and miRNA-378 for brain metastases in non-small-cell lung cancer.
Patients who received a curable surgery for their lung cancer were screened according to our criteria. Formalin-fixed paraffin-embedded samples from the patients were examined for the expression of miRNA-328 and miRNA-378 using real-time polymerase chain reaction and the expression of N-cadherin, E-cadherin, vascular endothelial growth factor, protein kinase Cα and S100B were investigated using immunohistochemical staining.
In total, 86 patients were screened for this study and 23 patients were diagnosed with brain metastases during the follow-up period. Comparing patients with and without brain metastases, the expression of miRNA-328 and miRNA-378 in tumor tissues were significantly different (P = 6.2 × 10(-5) and P = 2.8 × 10(-5), respectively). For the patients with brain metastases, the expression of miRNA-328 and miRNA-378 in tumor tissues compared with para-carcinoma tissues were also significantly different (P = 2.2 × 10(-5) and P = 1.6 × 10(-5), respectively). For patients with brain metastases, the association between miRNA-328 and protein kinase Cα was significant (r = 0.591, P = 0.003), but that between miRNA-378 and protein kinase Cα was not significant (r = 0.259, P = 0.232).
The expression of miRNA-328 and miRNA-378 in tumor tissues can be used to predict brain metastases in patients with non-small-cell lung cancer. miRNA-328 might promote brain metastases by regulating the expression of protein kinase Cα. However, the mechanisms of miRNA-378 to promote brain metastases should be studied in the future.
非小细胞肺癌患者脑转移的发生率差异很大，分子标志物被认为可预测脑转移。因此，本研究旨在确定miRNA - 328和miRNA - 378对非小细胞肺癌脑转移的预测价值及潜在机制。
根据我们的标准筛选接受肺癌根治性手术的患者。采用实时聚合酶链反应检测患者福尔马林固定石蜡包埋样本中miRNA - 328和miRNA - 378的表达，并采用免疫组织化学染色研究N - 钙黏蛋白、E - 钙黏蛋白、血管内皮生长因子、蛋白激酶Cα和S100B的表达。
本研究共筛选出86例患者，随访期间23例患者被诊断为脑转移。比较有和无脑转移的患者，肿瘤组织中miRNA - 328和miRNA - 378的表达有显著差异（分别为P = 6.2×10⁻⁵和P = 2.8×10⁻⁵）。对于有脑转移的患者，肿瘤组织中miRNA - 328和miRNA - 378与癌旁组织相比也有显著差异（分别为P = 2.2×10⁻⁵和P = 1.6×10⁻⁵）。对于有脑转移的患者，miRNA - 328与蛋白激酶Cα之间的相关性显著（r = 0.591，P = 0.003），但miRNA - 378与蛋白激酶Cα之间的相关性不显著（r = 0.259，P = 0.232）。
肿瘤组织中miRNA - 328和miRNA - 378的表达可用于预测非小细胞肺癌患者的脑转移。miRNA - 328可能通过调节蛋白激酶Cα的表达促进脑转移。然而，miRNA - 378促进脑转移的机制有待进一步研究。
