LMO2 Is a Novel Predictive Marker for a Better Prognosis in Pancreatic Cancer
LMO2 Is a Novel Predictive Marker for a Better Prognosis in Pancreatic Cancer
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DOI：
10.1593/neo.09418
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发表时间：
2009-07-01
期刊：
影响因子：
4.8
通讯作者：
Tsuneyoshi, Masazumi
中科院分区：
文献类型：
--
作者：
Nakata, Kohei;Ohuchida, Kenoki;Tsuneyoshi, Masazumi
目得：LIM结构域2（LMO 2）已被确定为与多种恶性肿瘤的致癌作用和更好的预后相关的新型癌基因。我们研究LMO 2在胰腺癌中的参与。实验设计：我们通过定量逆转录-聚合酶链反应和免疫组化评价了LMO 2在胰腺癌培养细胞、大块组织和显微切割细胞中的表达。结果：在164例胰腺癌中，98例（60%）LMO 2表达阳性。LMO 2在高级别胰腺上皮内瘤变（PanIN）病变（PanIN-2和-3）中的检出率高于低级别PanIN病变（PanIN-1A和-1B; P <0.001），在正常胰腺导管上皮中未检出。LMO 2信使RNA水平显着高于浸润性导管癌细胞比正常胰腺细胞的定量逆转录-聚合酶链反应分析的显微切割细胞（P = 0.036）。我们还发现LMO 2在组织学分级G1/G2癌中的表达率高于G3级癌（P <0.001）。LMO 2阳性患者的中位生存时间明显长于LMO 2阴性患者（P < .001），多变量分析显示LMO 2高表达是生存期延长的独立预测因子（风险比，0.432，P < .001）。即使在手术切缘阳性的患者中，与LMO 2阴性患者相比，LMO 2阳性患者也具有显著的生存获益。我们进一步进行了一项大型队列研究（n = 113），以检查福尔马林固定石蜡包埋样本中的LMO 2信使RNA水平，并发现了类似的结果。结论：LMO 2是一个很有前途的标志物，可以预测胰腺癌的预后。
PURPOSE: LIM domain only 2 (LMO2) has been identified as a novel oncogene associated with carcinogenesis and better prognosis in several malignant tumors. We investigate the involvement of LMO2 in pancreatic cancer. EXPERIMENTAL DESIGN: We evaluated LMO2 expression in cultured cells, bulk tissues, and microdissected cells from pancreatic cancers by quantitative reverse transcription-polymerase chain reaction and immunohistochemistry. RESULTS: Of 164 pancreatic cancers, 98 (60%) were positive for LMO2 expression. LMO2 was more frequently detected in high-grade pancreatic intraepithelial neoplasia (PanIN) lesions (PanIN-2 and -3) than in low-grade PanIN lesions (PanIN-1A and -1B; P < .001) and was not detected in normal pancreatic ductal epithelium. The LMO2 messenger RNA levels were significantly higher in invasive ductal carcinoma cells than in normal pancreatic cells as evaluated by quantitative reverse transcription-polymerase chain reaction analyses of microdissected cells (P = .036). We also found higher incidence of LMO2 expression in histologic grade G1/G2 cancers than in grade G3 cancers (P < .001). The median survival time of LMO2-positive patients was significantly longer than that of LMO2-negative patients P < .001), and multivariate analyses revealed that high LMO2 expression was an independent predictor of longer survival ( risk ratio, 0.432, P < .001). Even among patients with a positive operative margin, LMO2-positive patients had a significant survival benefit compared with LMO2-negative patients. We further performed a large cohort study (n = 113) to examine the LMO2 messenger RNA levels in formalin-fixed paraffin-embedded samples and found similar results. CONCLUSIONS: LMO2 is a promising marker for predicting a better prognosis in pancreatic cancer.