Clinical significance of TROP2 expression in colorectal cancer
Clinical significance of TROP2 expression in colorectal cancer
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DOI：
10.1158/1078-0432.ccr-05-1961
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发表时间：
2006-05-15
影响因子：
11.5
通讯作者：
Mori, Masaki
中科院分区：
文献类型：
--
作者：
Ohmachi, Takahiro;Tanaka, Fumiaki;Mori, Masaki
目的和实验设计：为了确定癌症相关基因，大肠癌细胞和正常上皮细胞的表达谱进行了检查和比较，使用激光显微切割和cDNA微阵列分析。从这些组合技术中，鉴定了几种癌症相关基因，包括TROP 2。TROP 2被称为钙信号转导子，在几种类型的肿瘤中高度表达。然而，还没有研究探讨TROP 2表达在结直肠癌中的意义。结果：激光显微切割和cDNA微阵列分析显示，在74例大肠癌组织中有84个基因过表达。其中一个高度过表达的基因是TROP 2。实时荧光定量RT-PCR结果显示，TROP 2在胃癌组织中的表达明显高于正常组织（P < 0.001）。将样品分为高（n = 26）和低（n = 48）TROP 2表达组。TROP 2高表达组肝转移率高（P = 0.005），死亡率高（P = 0.046）。胃癌浸润深度越深（P = 0.064），淋巴结转移越多（P = 0.125）。有趣的是，具有高TR 0 P2表达的肿瘤的患者具有较差的预后（P = 0.0036）。多因素分析显示，TROP 2的表达状态是影响结直肠癌预后的独立因素（相对危险度为2.38，95%可信区间为1.29-4.74; P < 0.01）。因此，TROP 2可能成为结直肠癌诊断和分子靶向治疗的候选基因。
Purpose and Experimental Design: To identify cancer-related genes, the expression profiles of colorectal cancer cells and normal epithelial cells were examined and compared using laser microdissection and cDNA microarray analysis. From these combined techniques, several cancer-related genes, including TROP2, were identified. TROP2 is known as a calcium signal transducer and is highly expressed in several types of tumors. However, no studies have investigated the significance of TROP2 expression in colorectal cancer. Thus, the expression status of TROP2 was investigated in 74 colorectal cancer samples by quantitative real-time reverse transcription-PCR and immunohistochemical studies.Results: Laser microdissection and cDNA microarray analysis showed that there were 84 overexpressed genes in cancer cells. One of the highly overexpressed genes was TROP2. Quantitative real-time reverse transcription-PCR showed that TROP2 expression in cancer samples was significantly higher than in normal samples (P < 0.001). The samples were divided into high (n = 26) and low (n = 48) TROP2 expression groups. The cases with high TROP2 expression showed a higher frequency of liver metastasis (P = 0.005) and more cancer-related death (P = 0.046). Those cases also had an inclination of deeper depth of invasion (P = 0.064) and more lymph node metastasis (P = 0.125). Interestingly, the patients with high TROP2 expression tumors had poorer prognosis (P = 0.0036). Multivariate analysis showed that TROP2 expression status was an independent prognostic factor (relative risk, 2.38; 95% confidence interval, 1.29-4.74; P < 0.01).Conclusion: TROP2 is one of the cancer-related genes that correlates with biological aggressiveness and poor prognosis of colorectal cancer. Thus, TROP2 is a possible candidate gene for diagnosis and molecular target therapy of colorectal cancer.