Department of Clinical Oncology, Queen Elizabeth Hospital, 30 Gascoigne Road, Kowloon, Hong Kong.
Br J Cancer. 2010 Jun 8;102(12):1731-5. doi: 10.1038/sj.bjc.6605700. Epub 2010 May 25.
Lung cancer is known as the top cancer killer in most developed countries. However, there is currently no promising diagnostic or prognostic biomarker for lung cancer. This study aims to discover non-invasive differential markers in the serum of lung cancer patients, to determine the protein identity of the candidate biomarker(s), and to investigate any clinical implication of the biomarker(s) concerned.
Blood specimens were collected from 154 pre-operative patients with lung cancer and 35 healthy blood donors with no evidence of lung cancer. Fractionated serum samples were processed by surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (MS). Candidate biomarker was identified using sodium dodecyl sulphate polyacrylamide gel electrophoresis and tryptic digestion followed by tandem MS fragmentation analysis, which was subsequently validated with immunoassay.
A differential protein with m/z 11.6 kDa was detected and identified as an isoform of human serum amyloid A (SAA). It was significantly increased by 1822% in lung cancer patients when compared with the healthy controls, which gave an area under the receiver operator characteristic curve of 0.88. In addition, the protein was also significantly elevated by 77% in lung cancer patients with survival <5 years when compared with patients with survival > or =5 years.
There are several functions of the SAA protein, described in the context of inflammation, that are compatible with the mechanism of tumour invasion and metastasis. Our study not only detected increased SAA level in the serum of lung cancer patients but also identified that elevated SAA level may be a non-invasive biomarker useful for the prediction of lung cancer prognosis.
肺癌是大多数发达国家的头号癌症杀手。然而,目前尚无有前途的肺癌诊断或预后生物标志物。本研究旨在发现肺癌患者血清中的非侵入性差异标志物,确定候选生物标志物的蛋白质身份,并研究生物标志物的任何临床意义。
从 154 名术前肺癌患者和 35 名无肺癌证据的健康献血者采集血液标本。通过表面增强激光解吸/电离飞行时间质谱(MS)对分级血清样本进行处理。使用十二烷基硫酸钠聚丙烯酰胺凝胶电泳和胰蛋白酶消化后进行串联 MS 碎片分析来鉴定候选生物标志物,随后使用免疫测定法进行验证。
检测到并鉴定出 m/z 为 11.6 kDa 的差异蛋白,其为人血清淀粉样蛋白 A(SAA)的同工型。与健康对照组相比,肺癌患者中的蛋白水平显著增加了 1822%,其受试者工作特征曲线下面积为 0.88。此外,与生存时间> 5 年的患者相比,生存时间<5 年的肺癌患者中的蛋白水平也显著升高了 77%。
SAA 蛋白具有几种功能,在炎症背景下描述,与肿瘤侵袭和转移的机制相兼容。我们的研究不仅检测到肺癌患者血清中 SAA 水平升高,而且还确定升高的 SAA 水平可能是一种非侵入性生物标志物,可用于预测肺癌预后。