利用MALDI质谱成像分析癌变生物标志物

生物标志物（Biomarker）是指可以标记系统、器官、组织、细胞及亚细胞结构或功能改变或可能发生改变的生化指标，其具有非常广泛的用途，目前生物标志物可用于疾病诊断、判断疾病分期或用来评价新药或新疗法在目标人群中的安全性及有效性。生物标志物能反映正常生理过程或病理过程或对治疗干预的药物反应，在早期诊断、疾病预防、药物靶点确定、药物反应以及其他方面发挥作用，寻找和发现有价值的生物标记物已经成为目前研究的一个重要热点。

基于分子癌症生物标志物的研究至少有如下3种重要用途, 即预测癌症的发生和疾病的早期检测; 提供治疗上的指导, 以及帮助确认药物研制的新靶点。癌症生物标志物的出现可能预示着一个时代的到来, 在这个时代医生将不再安排建立在种群统计基础上的治疗选择, 而是更正确地根据病人个体及其肿瘤的特性进行治疗选择。

本方案提供了一个在分子水平，使用HTX基质喷雾仪进行组织样品前处理，然后用超高分辨质谱成像方法研究癌变组织中的标志物分布，该方法可以推广到其它任何FFPE癌变组织。

Figure 1. Example N-glycan signal from a single section of thyroid cancer. A Total average spectrum from the image with example glycoform structures per m/z; B Tile view of example images. Inset top right, photomicrograph of unstained tissue prior to imaging. Abbreviations: GlcNAc, N-acetylglucosamine.

Figure 2. Image segmentation showing complexity of N-glycan signatures in a thyroid cancer tissuesection. A Pathologist marked H&E stain of section highlighting adjacent nontumor, anaplastic, and necrotic regions. B SCiLS image segmentation of N-glycans from 2D mapping. White asterisks markcalculated overlaps of anaplastic and necrotic regions.

Figure 3. Quantification of N-glycan signatures from regional areas on tissue. Statistical testing was donecomparing nontumor adjacent and anaplastic regions (ROC-1) or anaplastic versus necrotic (ROC-2).A Photomicrograph depicting areas selected for measuring relative abundance of N-glycan expression.B A high mannose (Man9) structure distinguishing nontumor adjacent compared to anaplastic tumor ornecrotic regions. C A biantennary N-glycan defining necrotic regions with low expression in nontumoradjacent and anaplastic. D A tetrantennary fucosylated structure with low expression in adjacent nontumor and increasing expression in anaplastic and necrotic tissues regions.