Gene Expression Profiles can predict the origin of the primary and metastastic liver adenocarcinoma

研究结果肝内胆管细胞癌(ICC)是肝脏第二常见的恶性肿瘤，近年来其发病率呈上升趋势。在各种癌症中，肝脏是癌症转移的常见部位。腺癌是一种常见的组织学类型的癌症。胃肠道肿瘤组织学上以腺癌居多。这些恶性肿瘤的治疗和预后各不相同。原发性肝内胆管细胞癌和转移性腺癌是不可能区分的。在本研究中，我们应用DNA微阵列技术来确定肝脏恶性肿瘤的来源。使用Affymetrix U133A plus2.0基因芯片，包含大约57000个转录本(Affymetrix，美国)，从40例原发性和转移性肝腺癌患者(肝内胆管癌n=11，结直肠癌转移n=20，胃癌转移n=8)中提取RNA。使用无监督和有监督的类别预测方法来识别能够区分这三个群体的基因标记。用非监督聚类方法成功地对三组样本进行了聚类。基因表达谱确定了一个126个基因的特征，可以区分这三个群体。前瞻性地，这一签名在9名独立患者中得到了验证。准确率为98%。综上所述，我们表明基因表达谱可以阐明肝腺癌的起源。

RESEARCH RESULTSIntrahepatic cholangiocarcinoma (ICC) is the second most common malignant tumor of the liver, and ICC is reportedly increasing recently. Liver is a frequent site of metastasis from cancer in various cancers. Adenocarcinoma is a popular histological type of cancer. Most of the gastrointestinal cancer is adenocarcinoma histologically. The treatment and prognosis differ for patients with these malignancies. The distinction between primary intrahepatic cholangiocarcinoma and metastatic adenocarcinoma is impossible. In this study, we applied DNA microarray technology to determine the origin of liver malignant tumors. Using Affymetrix U133A plus2.0 Gene Chip containing approximately 57000 transcripts (Affymetrix, USA), RNA samples from 40 patients with primary and metastatic liver adenocarcinomas (intrahepatic cholangiocarcinoma n=11, metastases from colorectal cancer n=20, metastases from gastric cancer n=8). Unsupervised and supervised class prediction approaches were used to identify gene markers that can discriminate the three groups. Three groups were successfully clustered by unsupervised clustering. Gene expression profiling identified a 126-gene signature that can discriminate the three groups. Prospectively, this signature was validated in 9 independent patients. The accuracy was 98%. In conclusion, we showed that gene expression profiling could elucidate the origin of the liver adenocarcinomas.