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位于X染色体上的癌-睾丸抗原在结直肠癌中的低频率和低表达:对南非人群免疫治疗的意义

Infrequent and low expression of cancer-testis antigens located on the X chromosome in colorectal cancer: implications for immunotherapy in South African populations.

作者信息

Dakshinamurthy Amirtha Ganesh, Ramesar Rajkumar, Goldberg Paul, Blackburn Jonathan M

机构信息

Department of Biotechnology, University of the Western Cape, Cape Town, South Africa.

出版信息

Biotechnol J. 2008 Nov;3(11):1417-23. doi: 10.1002/biot.200800144.

Abstract

Cancer-testis (CT) antigens are a group of tumor antigens that are expressed in the testis and aberrantly in cancerous tissue but not in somatic tissues. The testis is an immune-privileged site because of the presence of a blood-testis barrier; as a result, CT antigens are considered to be essentially tumor specific and are attractive targets for immunotherapy. CT antigens are classified as the CT-X and the non-X CT antigens depending on the chromosomal location to which the genes are mapped. CT-X antigens are typically highly immunogenic and hence the first step towards tailored immunotherapy is to elucidate the expression profile of CT-X antigens in the respective tumors. In this study we investigated the expression profile of 16 CT-X antigen genes in 34 colorectal cancer (CRC) patients using reverse transcription-polymerase chain reaction. We observed that 12 of the 16 CT-X antigen genes studied did not show expression in any of the CRC samples analyzed. The other 4 CT-X antigen genes showed low frequency of expression and exhibited a highly variable expression profile when compared to other populations. Thus, our study forms the first report on the expression profile of CT-X antigen genes among CRC patients in the genetically diverse South African population. The results of our study suggest that genetic and ethnic variations in population might have a role in the expression of the CT-X antigen genes. Thus our results have significant implications for anti-CT antigen-based immunotherapy trials in this population.

摘要

癌-睾丸(CT)抗原是一类肿瘤抗原,它们在睾丸中表达,在癌组织中异常表达,但在体细胞组织中不表达。由于存在血睾屏障,睾丸是一个免疫豁免部位;因此,CT抗原被认为基本上是肿瘤特异性的,是免疫治疗的有吸引力的靶点。根据基因所映射的染色体位置,CT抗原被分为CT-X抗原和非X CT抗原。CT-X抗原通常具有高度免疫原性,因此,定制免疫治疗的第一步是阐明CT-X抗原在各个肿瘤中的表达谱。在本研究中,我们使用逆转录-聚合酶链反应研究了34例结直肠癌(CRC)患者中16个CT-X抗原基因的表达谱。我们观察到,所研究的16个CT-X抗原基因中有12个在分析的任何CRC样本中均未显示表达。其他4个CT-X抗原基因显示出低表达频率,与其他人群相比,表现出高度可变的表达谱。因此,我们的研究形成了关于遗传多样性的南非人群中CRC患者CT-X抗原基因表达谱的第一份报告。我们的研究结果表明,人群中的遗传和种族差异可能在CT-X抗原基因的表达中起作用。因此,我们的结果对该人群中基于抗CT抗原的免疫治疗试验具有重要意义。

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