Insulin-like growth factor receptor-1 expression predicts postoperative recurrence in adenocarcinoma of the lung
Insulin-like growth factor receptor-1 expression predicts postoperative recurrence in adenocarcinoma of the lung
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DOI：
10.3892/etm.2011.258
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发表时间：
2011-07-01
影响因子：
2.7
通讯作者：
Tanaka, Fumihiro
中科院分区：
文献类型：
--
作者：
Nakagawa, Makoto;Uramoto, Hidetaka;Tanaka, Fumihiro
并非所有肺癌患者在完全切除后都需要术后辅助化疗。然而，对于选择合适的候选人或预测临床复发，没有有用的标记物存在。本研究的目的是阐明胰岛素样生长因子受体-1 （IGFR1）在肺腺癌中的临床作用。我们收集了182例肺腺癌完全切除患者的肿瘤标本。免疫组织化学检测IGFR1的表达。通过pcr分析，研究了表皮生长因子受体（EGFR）和K-ras基因的遗传状况。采用免疫组织化学和实时PCR检测分别评估MET基因与酪氨酸磷酸化和肝细胞生长因子（HGF）状态及扩增的关系。182例中有43例（23.6%）检测到IGFR1阳性表达。IGFR1阳性表达也分别在12例（42.9%）和31例（20.1%）复发和无复发患者中发现（p=0.009）。Logistic回归模型显示IGFR1表达阳性染色是与肿瘤复发相关的独立因素。IGFR1表达与较差的无病生存期（DFS）相关。多变量分析表明，IGFR1阳性表达与不良DFS风险增加独立相关。与野生型组相比，出现IGFR1阳性的肿瘤在K-ras突变组中更为常见。IGFR1表达与术后复发相关的DFS降低有关。因此，IGFR1的表达状态可以作为选择可能受益于辅助化疗的患者的候选替代标志物。
Not all patients with lung cancer require postoperative adjuvant chemotherapy after a complete resection. However, no useful markers exist for either selecting appropriate candidates or for predicting clinical recurrence. The purpose of the present study was to clarify the clinical role of insulin-like growth factor receptor-1 (IGFR1) in lung adenocarcinoma. Tumor specimens were collected from 182 patients who underwent a complete resection for adenocarcinoma of the lung. The expression of IGFR1 was evaluated by immunohistochemistry. The genetic status of the epidermal growth factor receptor (EGFR) and K-ras genes was also investigated by PCR-based analyses. Immunohistochemistry and real-time PCR assays were used to evaluate the MET gene association with tyrosine phosphorylation and hepatocyte growth factor (HGF) status, and amplification, respectively. Positive expression of IGFR1 was detected in 43 (23.6%) of the 182 cases. A positive IGFR1 expression was also identified in 12 (42.9%) and 31 (20.1%) of the patients with and without recurrence, respectively (p=0.009). Logistic regression models indicated that positive staining for IGFR1 expression was an independent factor associated with tumor recurrence. IGFR1 expression was associated with a poorer disease-free survival (DFS). Multivariate analysis demonstrated positive IGFR1 expression to be independently associated with an increased risk for poor DFS. The tumors appearing positive for IGFR1 were more frequent among those with K-ras mutations when compared with the wild-type group. IGFR1 expression was associated with reduced DFS correlating with postoperative recurrence. Therefore, the expression status of IGFR1 can be a candidate surrogate marker to select patients who may benefit from adjuvant chemotherapy.