Is insulin-like growth factor binding protein 2 associated with metastasis in lung cancer?
Is insulin-like growth factor binding protein 2 associated with metastasis in lung cancer?
复制标题
胰岛素样生长因子结合蛋白2与肺癌转移相关吗？
DOI：
10.1007/s10585-014-9647-4
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发表时间：
2014-06-01
影响因子：
4
通讯作者：
Zhou, Jianhua
中科院分区：
文献类型：
--
作者：
Hu, Qinghua;Huang, Lingjin;Zhou, Jianhua
胰岛素样生长因子结合蛋白2（IGFBP2）参与许多上皮癌的进展。然而，其在非小细胞肺癌（NSCLC）（另一种类型的上皮癌）中的作用仍不清楚。我们用免疫组化方法检测了110例NSCLC患者手术切除肿瘤中IGFBP2的表达，其中37例有转移。比较IGFBP2在转移组和非转移组中的阳性表达率，并分析IGFBP2表达与转移和总生存期的相关性。我们还研究了IGFBP2在从原发性肺癌细胞培养物收集的微泡（MV）中的表达，以及在新切除的NSCLC肿瘤的不同位置，使用免疫印迹。肺癌组织中IGFBP2的阳性表达率为51.8%，转移组阳性表达率为70.3%，非转移组阳性表达率为42.5%，差异有统计学意义（P< 0.01）。淋巴结分期越高，阳性率越高。在大多数肿瘤中胞浆表达占主导地位。基于多变量回归分析，IGFBP2与转移和总生存率差相关（风险比：分别为3.56和3.23）。IGFBP2在从IGFBP2阳性细胞系收集的MV中可检测到，并且其表达在新切除的肿瘤的边缘区域中最丰富。IGFBP2与肺癌的转移和低生存率相关。它在微血管中的存在和肿瘤边缘区的高丰度表明它与转移的关系可能与NSCLC中的肿瘤微环境重塑有关。
Insulin-like growth factor binding protein 2 (IGFBP2) is involved in the progression of many epithelial cancers. However, its role in non-small cell lung cancer (NSCLC), another type of epithelial cancer, remains unclear. We detected IGFBP2 expression using immunohistochemistry in surgically resected tumors from 110 NSCLC patients, 37 of which had metastases. The positive rate of IGFBP2 expression was compared between the metastatic and the non-metastatic group, and correlations of IGFBP2 expression with metastasis and overall survival were analyzed. We also investigated the expression of IGFBP2 in microvesicles (MVs) collected from primary lung cancer cell cultures, and in different locations of newly resected NSCLC tumors, using immunoblotting. The overall positive rate of IGFBP2 expression in lung cancer was 51.8 % and it was significantly higher in the metastatic group than in the non-metastatic group (70.3 and 42.5 % respectively,p< 0.01). And the higher the lymph node stage, the higher the positive rate. Cytoplasmic expression was predominant in the majority of the tumors. Based on multivariate regression analysis, IGFBP2 was correlated with metastasis and poor overall survival (Hazard ratio: 3.56 and 3.23 respectively). IGFBP2 was detectable in the MVs collected from IGFBP2 positive cell lines, and its expression was most abundant in the marginal region of the newly resected tumors. IGFBP2 is associated with metastasis and poor survival of lung cancer. Its presence in MVs and high abundance in the marginal region of tumors suggest that its association with metastasis may be related to tumor microenviroment remodeling in NSCLC.