Department of Chemistry, Centre for Research in Mass Spectrometry, York University, 4700 Keele Street, Toronto, Ontario, Canada M3J 1P3.
Mass Spectrom Rev. 2010 Nov-Dec;29(6):945-61. doi: 10.1002/mas.20296.
Mass spectrometry (MS)-based proteomics is a rapidly developing technology for both qualitative and quantitative analyses of proteins, and investigations into protein posttranslational modifications, subcellular localization, and interactions. Recent advancements in MS have made tremendous impact on the throughput and comprehensiveness of cancer proteomics, paving the way to unraveling deregulated cellular pathway networks in human malignancies. In turn, this knowledge is rapidly being translated into the discovery of novel potential cancer markers (PCMs) and targets for molecular therapeutics. Head-and-neck cancer is one of the most morbid human malignancies with an overall poor prognosis and severely compromised quality of life. Early detection and novel therapeutic strategies are urgently needed for more effective disease management. The characterizations of protein profiles of head-and-neck cancers and non-malignant tissues, with unprecedented sensitivity and precision, are providing technology platforms for identification of novel PCMs and drug targets. Importantly, low-abundance proteins are being identified and characterized, not only from the tumor tissues, but also from bodily fluids (plasma, saliva, and urine) in a high-throughput and unbiased manner. This review is a critical appraisal of recent advances in MS-based proteomic technologies and platforms for facilitating the discovery of biomarkers and novel drug targets in head-and-neck cancer. A major challenge in the discovery and verification of these cancer biomarkers is the typically limited availability of well-characterized and adequately stored clinical samples in tumor and sera banks, collected using recommended procedures, and with detailed information on clinical, pathological parameters, and follow-up. Most biomarker discovery studies use limited number of clinical samples and verification of cancer markers in large number of samples is beyond the scope of a single laboratory. The validation of these potential markers in large sample cohorts in multicentric studies is needed for their translation from the bench to the bedside.
基于质谱（MS）的蛋白质组学是一种用于定性和定量分析蛋白质以及研究蛋白质翻译后修饰、亚细胞定位和相互作用的快速发展的技术。MS 的最新进展对癌症蛋白质组学的通量和全面性产生了巨大影响，为揭示人类恶性肿瘤中失调的细胞通路网络铺平了道路。反过来，这些知识正在迅速转化为发现新的潜在癌症标志物（PCM）和分子治疗靶点。头颈部癌症是最致命的人类恶性肿瘤之一，总体预后较差，生活质量严重受损。迫切需要早期发现和新的治疗策略，以更有效地进行疾病管理。对头颈部癌症和非恶性组织的蛋白质谱进行前所未有的敏感和精确的特征描述，为鉴定新的 PCM 和药物靶点提供了技术平台。重要的是，不仅可以从肿瘤组织中，而且可以从体液（血浆、唾液和尿液）中以高通量和无偏倚的方式鉴定和表征低丰度蛋白质。本综述批判性地评价了基于 MS 的蛋白质组学技术和平台的最新进展，这些技术和平台有助于发现头颈部癌症的生物标志物和新型药物靶点。在这些癌症生物标志物的发现和验证中，一个主要挑战是肿瘤和血清库中通常可用的经过充分特征描述和充分储存的临床样本数量有限，这些样本是按照推荐程序收集的，并且具有有关临床、病理参数和随访的详细信息。大多数生物标志物发现研究使用有限数量的临床样本，并且在单个实验室范围内无法验证大量样本中的癌症标志物。需要在多中心研究中对这些潜在标志物进行大样本队列的验证，以便将其从实验室转化到临床。
