Cancer:CCTα或可头颈癌和非小细胞肺癌的新生物标志物

2014-04-04 佚名 生物通

ERCC1(DNA切除修复交叉互补基因1)蛋白表达是非小细胞肺癌患者辅助化疗的疗效预测标志物,8F1是目前最常用于测定测定肺癌患者组织中ERCC1表达水平的单克隆抗体之一。由佛罗里达大学斯克里普斯研究所(TSRI)的科学家带领的一个研究小组曾经指出,8F1可识别另一种核抗原,这种抗原具有作为临床预后分析生物标志物的价值。目前,该研究小组确定了这种新的生物标志物,与头颈癌和非小细胞肺癌患者的较好预后

ERCC1(DNA切除修复交叉互补基因1)蛋白表达是非小细胞肺癌患者辅助化疗的疗效预测标志物,8F1是目前最常用于测定测定肺癌患者组织中ERCC1表达水平的单克隆抗体之一。由佛罗里达大学斯克里普斯研究所(TSRI)的科学家带领的一个研究小组曾经指出,8F1可识别另一种核抗原,这种抗原具有作为临床预后分析生物标志物的价值。

目前,该研究小组确定了这种新的生物标志物,与头颈癌和非小细胞肺癌患者的较好预后相关。这项研究可以帮助科学家们开发新的诊断和治疗方法,帮助医生为这些癌症患者确定最佳的长期治疗方案。

相关研究发表在2014年4月1日的Cancer杂志,集中在一个称为磷酸胆碱胞苷酸转移酶-αCCT-α(Choline phosphate cytidylyltransferase-α,CCTα)的蛋白质,这是可被8F1识别的另外那种抗原。研究人员采用质谱分析法鉴定了这种抗原,并通过敲除和过表达实验,确定了抗体的特异性。

TSRI的副教授Laura Niedernhofer和美国卡曼纽斯肿瘤研究所的Gerold Bepler指导了这项研究。Laura Niedernhofer博士指出:“根据我们的发现,CCTα的高表达似乎是存活的征兆,使CCTα成为一种很有前途的生物标志物。我们的研究结果表明,事实上,与已经建立的ERCC1相比,CCTα对于两种癌症患者的预后结果决定,可能更加的重要。”

目前,有大型临床试验利用ERCC1 DNA修复蛋白的表达,作为肺癌、胃癌、结肠直肠癌、食管癌或卵巢癌患者是否应该采用铂疗法(一种非常有效但有毒的DNA损伤药物)治疗的一个决定因素。

然而,这一新研究表明,这些阳性结果并不真正是因为ERCC1,而是CCTα——它也能够与最常用来测量ERCC1表达的抗体结合。Niedernhofer指出:“我们的研究结果表明,与ERCC1 表达相比,CCTα可能是患者预后的一个更好的预测因子。”

虽然ERCC1与DNA修复相关,但CCTα参与细胞膜主要成分的合成,活跃于膜介导的信号传递和胚胎存活中。

研究人员从187名非小细胞肺癌和60名头颈部鳞状细胞癌患者采集了样本,通过样本的免疫组化分析,来检测这种抗原对8F1免疫反应的影响,及与患者预后的关联。

CCTα表达与延长生存率有关,包括仅手术治疗而没有使用铂化疗药物及相关毒副作用的非小细胞癌患者。

原始出处:


Vaezi AE1, Bepler G, Bhagwat NR, Malysa A, Rubatt JM, Chen W, Hood BL, Conrads TP, Wang L, Kemp CE, Niedernhofer LJ.Choline phosphate cytidylyltransferase-α is a novel antigen detected by the anti-ERCC1 antibody 8F1 with biomarker value in patients with lung and head and neck squamous cell carcinomas.Cancer. 2014 Apr 1. doi: 10.1002/cncr.28643.

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    2014-06-14 wshxjq
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