Scanlan Matthew J, Welt Sydney, Gordon Claudia M, Chen Yao-Tseng, Gure Ali O, Stockert Elisabeth, Jungbluth Achim A, Ritter Gerd, Jäger Dirk, Jäger Elke, Knuth Alexander, Old Lloyd J
Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Cancer Res. 2002 Jul 15;62(14):4041-7.
Monitoring human antibody recognition of tumor antigens could have potential diagnostic and prognostic significance. Serological analysis of recombinant cDNA expression libraries of human cancer has identified a number of immunogenic tumor antigens. To identify colon cancer antigens associated with a cancer-related serum IgG response, serum samples from 74 patients with colon cancer and 75 normal blood donors were screened for antibody reactivity to 77 serologically defined tumor antigens. The following 13 antigens reacted exclusively with sera from the colon cancer patients and not with sera from normal blood donors: p53, MAGEA3, SSX2, NY-ESO-1, HDAC5, MBD2, TRIP4, NY-CO-45, KNSL6, HIP1R, Seb4D, KIAA1416, and LMNA. Serum samples from 34 of 74 (46%) colon cancer patients detected 1 or more of these 13 antigens. Fifty-three of 74 colon cancer patients were of known clinicopathological stage. Analysis of antibody frequency showed that 5 of 7 (71%) stage I colon cancer patients, 4 of 11 (36%) stage II patients, 2 of 14 (14%) stage III patients, and 11 of 21 (52%) stage IV patients had serum IgG antibody that reacted with 1 or more of the 13 antigens. The mRNA expression patterns of 8 of these 13 antigens were altered in cancer. Three of the 13 antigens were cancer/testis antigens (MAGEA3, SSX2, and NY-ESO-1), which are expressed exclusively in normal gametogenic tissues and aberrantly expressed in a broad range of cancer types. Quantitative real-time reverse transcription-PCR showed that the mRNA expression levels of 2 antigens, HDAC5 and Seb4B, were down-regulated in colon cancer, 2 other antigens, KNSL6 and KIAA1416, were up-regulated, and another antigen, NY-CO-45, showed a variable level of mRNA expression in colon cancer. With regard to KNSL6 mRNA expression, only trace levels were detected in 15 different normal tissues with the exception of testis, which showed a high level of KNSL6 mRNA expression. In contrast, 9 of 9 colon cancer specimens showed overexpression of KNSL6 mRNA, ranging from 5 to 44 times the level detected in normal colon tissue, indicating that this antigen could also be a valuable therapeutic target.
监测人类抗体对肿瘤抗原的识别可能具有潜在的诊断和预后意义。对人类癌症重组cDNA表达文库进行血清学分析已鉴定出多种免疫原性肿瘤抗原。为了鉴定与癌症相关血清IgG反应相关的结肠癌抗原，对74例结肠癌患者和75名正常献血者的血清样本进行了筛查，以检测其对77种血清学定义的肿瘤抗原的抗体反应性。以下13种抗原仅与结肠癌患者的血清反应，而不与正常献血者的血清反应：p53、MAGEA3、SSX2、NY-ESO-1、HDAC5、MBD2、TRIP4、NY-CO-45、KNSL6、HIP1R、Seb4D、KIAA-1416和LMNA。74例结肠癌患者中的34例（46%）血清样本检测到这13种抗原中的1种或更多种。74例结肠癌患者中有53例已知临床病理分期。抗体频率分析显示，7例I期结肠癌患者中有5例（71%）、11例II期患者中有4例（36%）、14例III期患者中有2例（14%）以及21例IV期患者中有11例（52%）的血清IgG抗体与这13种抗原中的1种或更多种发生反应。这13种抗原中的8种在癌症中的mRNA表达模式发生了改变。13种抗原中有3种是癌胚抗原（MAGEA3、SSX2和NY-ESO-1），它们仅在正常生精组织中表达，而在多种癌症类型中异常表达。定量实时逆转录PCR显示，2种抗原HDAC5和Seb4B的mRNA表达水平在结肠癌中下调，另外2种抗原KNSL6和KIAA1416上调，另一种抗原NY-CO-45在结肠癌中的mRNA表达水平变化不定。关于KNSL6 mRNA表达，除睾丸显示高水平的KNSL6 mRNA表达外，在15种不同正常组织中仅检测到微量水平。相比之下，9例结肠癌标本中有9例显示KNSL6 mRNA过表达，其水平是正常结肠组织中检测水平的5至44倍，表明该抗原也可能是一个有价值的治疗靶点。
