Cellmid Ltd., Sydney, NSW, Australia.
Br J Pharmacol. 2014 Jun;171(12):2925-39. doi: 10.1111/bph.12601.
Midkine (MK) is a pleiotropic growth factor prominently expressed during embryogenesis but down-regulated to neglible levels in healthy adults. Many published studies have demonstrated striking MK overexpression compared with healthy controls in various pathologies, including ischaemia, inflammation, autoimmunity and, most notably, in many cancers. MK expression is detectable in biopsies of diseased, but not healthy, tissues. Significantly, because it is a soluble cytokine, elevated MK is readily apparent in the blood and other body fluids such as urine and CSF, making MK a relatively convenient, accessible, non-invasive and inexpensive biomarker for population screening and early disease detection. The first diagnostic tests that quantify MK are just now receiving regulatory clearance and entering the clinic. This review examines the current state of knowledge pertaining to MK as a biomarker and highlights promising indications and clinical settings where measuring MK could make a difference to patient treatment. I also raise outstanding questions about reported variants of MK as well as MK's bio-distribution in vivo. Answering these questions in future studies will enhance our understanding of the significance of measured MK levels in both patients and healthy subjects, and may reveal further opportunities for measuring MK to diagnose disease. MK has already proven to be a biomarker that can significantly improve detection, management and treatment of cancer, and there is significant promise for developing further MK-based diagnostics in the future.
中期因子（MK）是一种多功能生长因子，在胚胎发生过程中表达明显，但在健康成年人中下调至可忽略的水平。许多已发表的研究表明，与健康对照组相比，MK 在各种病理情况下表达显著上调，包括缺血、炎症、自身免疫，尤其是在许多癌症中。MK 的表达在患病组织的活检中可检测到，但在健康组织中不可检测到。重要的是，由于它是一种可溶性细胞因子，MK 在血液和其他体液（如尿液和 CSF）中升高很容易被发现，这使得 MK 成为一种相对方便、可及、非侵入性和廉价的生物标志物，可用于人群筛查和早期疾病检测。目前，用于定量 MK 的第一个诊断测试刚刚获得监管批准并进入临床应用。这篇综述检查了 MK 作为生物标志物的当前知识状态，并强调了有希望的适应症和临床环境，在这些环境中，测量 MK 可以对患者治疗产生影响。我还提出了关于 MK 报告变体以及 MK 在体内生物分布的悬而未决的问题。在未来的研究中回答这些问题将增强我们对患者和健康受试者中测量的 MK 水平的意义的理解，并可能揭示进一步测量 MK 以诊断疾病的机会。MK 已经被证明是一种可以显著提高癌症检测、管理和治疗效果的生物标志物，未来开发进一步基于 MK 的诊断方法具有重要意义。
