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中国学者发现新型血浆蛋白有助诊断肺癌

Lung cancer diagnosis aided by novel plasma protein
来源:爱思唯尔 2013-09-18 16:57点击次数:876发表评论

中国医学科学院肿瘤医院胸外科的赫捷医生及其同事在《临床癌症研究》杂志上发表的一项大规模前瞻性研究显示,利用一种参与肿瘤氧化还原反应的血浆蛋白质,可在超过3/4的临床样本中检出和排除肺癌(Clin. Cancer. Res. 2013; 19: 5136-45)。


异柠檬酸脱氢酶1(IDH1)检测值在训练组样本中(n=712)的敏感性和特异性分别为77.1%和76.2%,在验证组样本中(n=710)的敏感性和特异性分别为76.2%和82.9%。


如果将这种蛋白质的检测值与其他已知的非小细胞肺癌(NSCLC)生物标志物综合考虑,在训练组和验证组中的敏感性还可进一步升至75.8%和86.3%,特异性则分别升至89.6%和70.7%。


赫捷医生


“一些已知的NSCLC生物标志物——例如CEA(癌胚抗原)和Cyfra21-1(细胞角蛋白碎片21-1)——已被用于临床实践,而诸如CA125(癌抗原125)等其他标志物则有待进一步验证。这些生物标志物的敏感性较低,仅有50%~60%,而特异性约为90%。”


这个研究小组此前已发现,NSCLC患者肿瘤标本中的IDH1水平升高(Mol. Cell. Proteomics 2012;11:M111)。本次发表的研究旨在确定这种蛋白质的检测值是否有助于诊断肺癌,是否能区分有和没有恶性疾病的患者。


研究者在2007~2011年期间从943例尚未接受治疗的NSCLC患者和479名参加常规体检的健康人那里采集了1,422份血样。来自肺癌患者的血样是在手术前3天时采集的,采集后立即通过酶联免疫吸附测定法(ELISA)确定IDH1水平,同时利用一种Elecys免疫分析仪检测CEA、Cyfra21-1和CA125水平。


结果显示,鳞癌患者(n=489)的IDH1中位水平比健康对照者高2.39 U/L,腺癌患者(n=454)的IDH1中位水平比健康对照者高1.96 U/L。而且,腺癌患者的血浆IDH1中位水平高于鳞癌患者(P=0.012)。


赫捷医生在美国癌症研究协会(AACR)举办的新闻发布会上指出:“我们发现,IDH1是一种可有效诊断NSCLC——尤其是肺腺癌——的血浆生物标志物,具有很高的敏感性和特异性。基于现有数据,IDH1可用于检测1期肺癌。”


赫捷医生指出,这种蛋白质也可被用于检测癌前病变,但这一用途有待进一步研究的验证。IDH1可能是NSCLC治疗的一个良好靶点。研究者计划开展一项多中心临床试验来更深入验证IDH1的诊断价值。


这项研究获得了中国高技术研究发展计划(863计划)、国际科技合作与交流计划、中国自然科学基金、中国教育部博士点专项基金和政府高干医疗保健研究基金的资助。作者无相关利益冲突披露。


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By: SARA FREEMAN, Internal Medicine News Digital Network


A plasma protein involved in tumor oxidation and reduction reactions was useful for detecting and excluding lung cancer in more than three quarters of clinical samples evaluated in a large prospective study.


Isocitrate dehydrogenase 1 (IDH1) measurement was associated with a sensitivity of 77.1% and specificity of 76.2% in a training set of samples (n = 712), and 82.9% sensitivity and 76.6% specificity in a second validation or test set (n = 710).


Sensitivity and specificity were generally improved when the protein’s detection was considered in addition to other known or proposed non–small-cell lung cancer (NSCLC) biomarkers, with sensitivities of 75.8% and 86.3% in the training and test sets, respectively, and specificities of 89.6% and 70.7%.


"Some existing NSCLC biomarkers, such as CEA [carcinoembryonic antigen] and Cyfra21-1 [cytokeratin fragment 21-1], have been used in clinical practice, whereas others, such as CA125 [cancer antigen 125], have been recommended for further validation," Dr. Nan Sun and associates reported in the latest issue of Clinical Cancer Research.


"These biomarkers have low sensitivity, ranging from 50% to 60%, with specificities of approximately 90%," said the researchers, of the department of thoracic surgical oncology at the Cancer Institute and Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences in Beijing.


Previous research by the team had shown IDH1 levels were elevated in tumor samples taken from patients with NSCLC (Mol. Cell. Proteomics 2012;11:M111). Their present investigation (Clin. Cancer. Res. 2013; 19: 5136-45) therefore aimed to see if the protein’s measurement could aid in the diagnosis of lung cancer, differentiating between those who did and those who did not have malignant disease.


For their investigation, the team obtained 1,422 blood samples from 943 patients with previously untreated NSCLC and 479 healthy individuals who were seen for routine examinations between 2007 and 2011 at their institution.


The blood samples from the lung cancer patients were taken 3 days prior to their undergoing surgery and IDH1 levels were immediately determined by enzyme-linked immunosorbent assay, while CEA, Cyfra21-1, and CA125 levels were measured with an Elecys immunoassay analyzer.


Median levels of IDH1 were 2.39 U/L higher than those of healthy controls for squamous cell carcinoma cases (n = 489) cases and 1.96 U/L higher for adenocarcinoma cases (n = 454). Additionally, median plasma levels of IDH1 were higher in patients with adenocarcinomas than in those with squamous cell carcinomas (P = .012)


"We have identified IDH1 as an effective plasma biomarker with high sensitivity and specificity in the diagnosis of NSCLC, especially lung adenocarcinoma," senior study investigator Dr. Jie He said in a press release issued by the American Association for Cancer Research. "Based on the present data, IDH1 can be used to detect stage 1 lung cancer,"


The protein might also detect precancerous lesions, but further studies are required to test that hypothesis, said Dr. He. IDH1 might be a good target for NSCLC treatment as it "may be involved in the development of lung cancer."


A multicenter clinical trial is planned to further validate the diagnostic utility of IDH1.


Research funding was provided by the National High Technology Research and Development Program of China, the International Science and Technology Corporation and Exchange Project, the National Natural Science Foundation of China, the Doctoral Fund of Ministry of Education of China, and the Government Health Care Research Foundation for Senior Officials. The authors had no conflicts of interest to disclose.
 


学科代码:呼吸病学 肿瘤学 检验病学   关键词:异柠檬酸脱氢酶1 非小细胞肺癌
来源: 爱思唯尔
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