The role of S100A6 in pancreatic cancer development and its clinical implication as a diagnostic marker and therapeutic target
The role of S100A6 in pancreatic cancer development and its clinical implication as a diagnostic marker and therapeutic target
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DOI：
10.1158/1078-0432.ccr-05-0714
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发表时间：
2005-11-01
影响因子：
11.5
通讯作者：
Tanaka, M
中科院分区：
文献类型：
--
作者：
Ohuchida, K;Mizumoto, K;Tanaka, M
最近的微阵列分析表明，S100家族包含的成员是候选的诊断标志物或治疗靶点。在本研究中，为了评估S100A6在胰腺癌中的参与及其临床诊断价值，我们检测了不同胰腺疾病患者胰腺组织和胰液中S100A6 mRNA的表达。为了研究S100A6在胰腺癌发生中的作用以及S100A6作为胰腺癌早期诊断标志物的潜力，我们对胰腺正常导管、胰腺上皮内瘤变和浸润性导管癌进行了免疫组织化学和基于显微解剖的mRNA分析。我们还使用体外实验和RNA干扰的微阵列分析来评估S100A6的功能作用及其作为胰腺癌治疗靶点的潜力。S100A6 mRNA在癌组织中的表达明显高于癌旁组织。在胰液中，S100A6在胰腺癌患者和非肿瘤性疾病患者中的表达有显著性差异，ROC曲线显示S100A6可能是诊断胰腺癌的一个有用的标志物。免疫组化和显微解剖分析显示S100A6在正常导管、胰腺上皮内瘤变和浸润性导管癌中的表达存在差异。体外研究表明，抑制S100A6可以降低癌细胞的增殖和侵袭力，这些发现得到了微阵列数据的支持。我们目前的研究结果表明，定量S100A6 mRNA是一个有前途的工具，用于诊断胰腺癌，S100A6可能是一个有前途的治疗靶点胰腺癌。
Recent microarray analyses showed that the S100 family contains members that are candidate diagnostic markers or therapeutic targets. In the present study, to evaluate the involvement of S100A6 in pancreatic cancer and its clinical usefulness for diagnosis, we examined S100A6mRNA expression in pancreatic tissues and pancreatic juice from patients with different pancreatic diseases. To investigate the role of S100A6 in carcinogenesis of pancreatic cancer and the potential of S100A6 as a diagnostic marker for early detection of pancreatic cancer, we did immunohistochemistry and microdissection-based mRNA analysis of pancreatic normal ducts, pancreatic intraepithelial neoplasias, and invasive ductal carcinomas. We also used in vitro experiments and microarray analysis with RNA interference to evaluate the functional role of S100A6 and its potential as a therapeutic target for pancreatic cancer. S100A6 mRNA levels were significantly higher in carcinoma specimens than in nonneoplastic tissues. In pancreatic juice, there was a significant difference in S100A6 expression between patients with carcinoma and those with nonneoplastic disease, Receiver operating characteristic curves revealed that S100A6 might be a useful marker for diagnosis of pancreatic cancer. Immunohistochemistry and microdissection-based analysis showed differential expression of S100A6 among normal ducts, pancreatic intraepithelial neoplasias, and invasive ductal carcinomas. In vitro data showed that inhibition of S100A6 decreased proliferation and invasiveness of cancer cells, and these findings were supported by microarray data. Our present results suggest that quantitation of S100A6 mRNA is a promising tool for diagnosis of pancreatic cancer, and that S100A6 may be a promising therapeutic target for pancreatic cancer.