Expression profile of cancer-testis genes in 121 human colorectal cancer tissue and adjacent normal tissue

Expression profile of cancer-testis genes in 121 human colorectal cancer tissue and adjacent normal tissue
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121例人结直肠癌组织及癌旁正常组织中癌睾丸基因的表达谱

DOI:
10.1158/1078-0432.ccr-04-1365
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发表时间:
2005-03-01
影响因子:
11.5
通讯作者:
Gu, J
Gu, J
中科院分区:
医学1区
文献类型:
--
作者:
Li, M;Yuan, YH;Gu, J

文献摘要

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目的:在迄今发现的肿瘤抗原中,由CT基因编码的癌睾丸(CT)抗原被确定为一组极具吸引力的癌症疫苗靶点。本研究首次分析了大队列结直肠癌(CRC)患者中多个CT基因的mRNA表达及其与病理特征的可能相关性。实验设计:采用RT-PCR方法分析121例结直肠癌及癌旁组织中10个CT基因的表达。ELISA法检测血清样品中NY-ESO-1抗体的存在。为了证实蛋白的表达,免疫组化检测NY-ESO-1抗原在mrna阳性的结直肠癌组织中的表达。结果:CRC组织中有不同频率的CT基因,SCP-1, 1.7%;SSX-2,: 2.5%;SSX-4, 2.5%;SSX-1, 5.0%;CT10, 6.6%;NY-ESO-1, 9.9%;MAGE-1, 11.6%;LAGE-1, 15.7%;MAGE-4, 22.3%;和MAGE-3, 27.3%。在本研究检查的56.2%的肿瘤组织中至少检测到一个CT基因。而癌旁组织未见CT基因表达。在研究的10个CT基因中,NY-ESO-1和LAGE-1是特别感兴趣的,因为它们的mRNA在CRC中的表达以前很少报道。在我们的研究中,NY-ESO-1 mRNA在9.9%的样本中表达,并且与分期(P = 0.041)和局部淋巴结转移(P = 0.002)显著相关。此外,我们还鉴定了一份NY-ESO-1抗体阳性的血清样本。MAGE-4 mRNA在血管栓塞的肿瘤组织中表达频率较高(P = 0.025)。结论:这些结果提示CT基因,特别是NY-ESO-1和LAGE-1在结直肠癌中确实表达。在本研究中,超过50%的CRC患者至少表达一种CT基因,这使得他们有资格接种CT疫苗。NY-ESO-1基因可能作为局部转移和疾病进展的标志。MAGE-4基因与血管栓塞有显著相关性。
Purpose: Among tumor antigens identified to date, cancer-testis (CT) antigens, which are coded by CT genes, are identified as a group of highly attractive targets for cancer vaccines. This study is the first to analyze the mRNA expression and possible correlation with pathologic characteristics of multiple CT genes in a large cohort of colorectal cancer (CRC) patients.Experimental Design: The expression of 10 individual CT genes in 121 CRC and adjacent tissues were analyzed by RT-PCR method. The presence of autologous antibodies against NY-ESO-1 was examined in serum samples by ELISA. To confirm the protein expression, immunohistochemistry was done for detecting the NY-ESO-1 antigen in mRNA-positive CRC tissues.Results: The CT genes were detected with various frequencies in CRC tissue, SCP-1, 1.7%; SSX-2, :2.5%; SSX-4,2.5%; SSX-1, 5.0%; CT10, 6.6%; NY-ESO-1, 9.9%; MAGE-1, 11.6%; LAGE-1, 15.7%; MAGE-4, 22.3%; and MAGE-3, 27.3%. In 56.2% of tumor tissues examined in this study, at least one CT gene was detected. In contrast, no CT gene expression was found in cancer adjacent tissues. Among 10 CT genes investigated, NY-ESO-1 and LAGE-1 are of particular interest because their mRNA expression in CRC was rarely reported before. In our study, NY-ESO-1 mRNA was found to express in 9.9% of the samples, and also correlated significantly with stages (P = 0.041) and local lymph node metastasis (P = 0.002). In addition, we also identified one NY-ESO-1 antibody-positive serum sample. MAGE-4 mRNA was expressed at a high frequency in tumor tissues with vessel emboli samples (P = 0.025).Conclusions: These results suggested that CT genes, especially NY-ESO-1 and LAGE-1, do express in CRC. More than 50% of the CRC patients in this study express at least one CT gene, making them eligible for CT vaccination. NY-ESO-1 gene may serve as a marker for local metastasis and advanced disease. MAGE-4 gene is significantly associated with the vessel emboli.