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Cancer:预示头颈部癌患者生存的新型生物标志物

来源:生物谷 2014-04-03 20:32

来自Florida campus of The Scripps Research Institute (TSRI)的研究小组发现了一种新的生物标记,或能预示头颈部癌症患者、非小细胞肺癌患者的疾病结果。这项工作可以帮助科学家开发出新的诊断和治疗。

研究结果发表在Cancer杂志上,研究人员关注于胆碱磷酸胞苷酰转移酶-α,即CCT-α,CCT-α是一种抗原,促进免疫系统产生抗体并结合CCT-α(抗原)。

根据研究人员发现,高CCTα表达似乎能预示患者的生存情况,使得CCTα将成为一个有前途的生物标志物,TSRI副教授Laura Niedernhofer说:我们的研究结果表明,CCTα可能事实上,在确定这两种类型癌症患者的生存结果中,比已知的生物标志物ERCC1更重要。

目前,几十个大型临床试验正在使用ERCC1 DNA修复蛋白的表达,作为肺癌,胰腺癌,胃癌,大肠癌,食管癌,卵巢癌患者是否应接受铂类药物治疗的判断指标。然而,新的研究表明,有些阳性结果实际上不是由于ERCC1所引发的,而是CCTα(其结合抗体,抗体是最常用来测量ERCC1基因蛋白表达)。Niedernhofer说:我们的研究结果表明在预测患者的治疗效果方面,相比于ERCC1的表达,CCTα可能是一个更好的指标。

ERCC1与DNA修复有关,CCTα参与细胞膜主要成分的合成,在膜介导的信号传导和胚胎存活中发挥活性。新的研究结果是基于检查187例非小细胞肺癌和60例头颈部鳞状细胞癌样本获得的。(生物谷Bioon.com)


 

doi:10.1002/cncr.28643
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

Alec E. Vaezi MD, PhD,et al.

BACKGROUND
The determination of in situ protein levels of ERCC1 with the 8F1 monoclonal antibody is prognostic of survival in patients with non-small cell lung cancer (NSCLC). The authors previously demonstrated that 8F1 recognizes a second nuclear antigen. This antigen was identified and its value as a biomarker of clinical outcomes analyzed.

METHODS
The second antigen was identified by mass spectrometry. Protein identity and antibody specificity were confirmed through knockdown and overexpression experiments. Immunohistochemistry of 187 early-stage NSCLC samples and 60 head and neck squamous cell carcinomas (HNSCCs) was used to examine the influence of the second antigen on 8F1 immunoreactivity and its association with patient outcomes.

RESULTS
Choline phosphate cytidylyltransferase-α (CCTα, also known as phosphate cytidylyltransferase 1 choline alpha [PCYT1A], a phospholipid synthesis enzyme regulated by RAS) is the second antigen recognized by 8F1. In NSCLC samples, CCTα contributed (rho, 0.38) to 8F1 immunoreactivity. In samples of squamous cell carcinomas of the lung, CCTα was found to be the dominant determinant of 8F1 immunoreactivity, whereas its contribution in other subtypes of lung cancer was negligible. High expression of CCTα, but not ERCC1, was found to be prognostic of longer disease-free survival (log-rank P=.002) and overall survival (log-rank P=.056). Similarly, in patients with HNSCC, CCTα contributed strongly to 8F1 immunoreactivity (rho, 0.74), and high CCTα expression was found to be prognostic of survival (log-rank P=.022 for disease-free survival and P=.027 for overall survival).

CONCLUSIONS
CCTα is the second antigen detected by 8F1. High CCTα expression appears to be prognostic of survival in patients with NSCLC who are treated by surgery alone and patients with HNSCC. CCTα is a promising biomarker of patient survival and deserves further study.

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