发现关键生物标志物!新成果为肺癌早期诊断带来希望
2018/05/10
来自日本科学家们的一项最新研究发现,肺癌患者血液中的细胞骨架相关蛋白4 (CKAP4)水平显著高于健康个体。研究人员还确定,CKAP4水平在I期疾病患者的血液中就已经升高,这使其有望成为一种潜在的无创诊断标志物,用以改变某些肺癌(包括非小细胞肺癌和鳞状细胞癌等)当前的诊断和治疗方法,并改善患者的预后。

图片来源:cityofhope

这项最新结果于5月8日发表在《美国病理学杂志》上,文章题为“Cytoskeleton-Associated Protein 4 Is a Novel Serodiagnostic Marker for Lung Cancer”,日本北佐藤大学(Kitasato University)的Ryo Nagashio博士与Yuichi Sato博士分别为通讯作者及主要作者。

https://doi.org/10.1016/j.ajpath.2018.03.007

Ryo Nagashio博士说:“目前肺癌的生物标志物包括癌胚抗原(CEA)、sialyl Lewis X抗原(SLX)、鳞状细胞癌(SCC) 抗原和细胞角蛋白片段(CYFRA)21-1,但是这些生物标志物对早期检测肿瘤不够敏感,而我们的研究提供的证据表明,CKAP4蛋白可能是一种新的肺癌早期血清诊断标志物。”

为了开发这种肺癌血清诊断标志物,进一步研究一种能够识别CKAP4的、叫做KU-Lu-1的抗体以及评价该抗体作为肺癌血清学诊断标志物的应用价值,研究人员对271例肺癌患者和100例健康人的血清进行了反相蛋白阵列分析(reverse-phase protein array analysis)。

试验发现,血清CKAP4水平可区分肺癌患者和健康对照者。I期腺癌或鳞状细胞癌患者血清CKAP4水平高于健康对照组(P < 0.0001),而在I期非小细胞肺癌中也检测到了CKAP4水平的升高。接下来的验证试验同样证实肺癌患者血清CKAP4水平显著高于健康对照组(P < 0.0001),这提示CKAP4可能是一种新的肺癌早期血清学诊断指标。

之前实验表明,在疾病I - IV期,血清CEA、CYFRA和SCCA的敏感性分别为30%-52%、17%-82%和24%-39%。在最新研究中,科学家们得出,血清CKAP4的敏感性在训练组(training set)为81%,在验证组为69%,均高于目前的血清诊断标志物的敏感性。

随后,通过免疫沉淀和质谱分析,该小组确定KU-Lu-1抗体能够在肺癌细胞和组织中识别CKAP4,并证实其分泌到培养上清液中。进一步地,研究人员还利用100例肺癌患者和38例健康对照者对研究结果进行了验证。

“使用CKAP4作为生物标志物可以改变目前治疗肺癌患者的做法。此外,通过CKAP4与常规标志物的组合可以显著提高诊断准确性。”Sato博士总结道。

责编:艾曼

参考资料:

Lung Cancer Biomarker Discovery Raises Hopes for Early Detection

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  • Cytoskeleton-Associated Protein 4 Is a Novel Serodiagnostic Marker for Lung Cancer

    Our aim was to develop a serodiagnostic marker for lung cancer. Monoclonal antibodies were generated, and one antibody designated as KU-Lu-1, recognizing cytoskeleton-associated protein 4 (CKAP4), was studied further. To evaluate the utility of KU-Lu-1 antibody as a serodiagnostic marker for lung cancer, reverse-phase protein array analysis was performed with sera of 271 lung cancer patients and 100 healthy controls. CKAP4 was detected in lung cancer cells and tissues, and its secretion into the culture supernatant was also confirmed. The serum CKAP4 levels of lung cancer patients were significantly higher than those of healthy controls (P < 0.0001), and the area under the curve of receiver-operating characteristic curve analysis was 0.890, with 81.1% sensitivity and 86.0% specificity. Furthermore, the serum CKAP4 levels were also higher in patients with stage I adenocarcinoma or squamous cell carcinoma than in healthy controls (P < 0.0001). Serum CKAP4 levels may differentiate lung cancer patients from healthy controls, and they may be detected early even in stage I non–small cell lung cancer. Serum CKAP4 levels were also significantly higher in lung cancer patients than in healthy controls in the validation set (P < 0.0001). The present results provide evidence that CKAP4 may be a novel early serodiagnostic marker for lung cancer.

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