Clinically meaningful molecular subtypes for classification of breast cancers have been established, however, initiation and progression of these subtypes remain poorly understood. The recent development of desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) facilitates the convergence of analytical chemistry and traditional pathology, allowing chemical profiling with minimal tissue pretreatment in frozen samples. Here, we characterized the chemical composition of molecular subtypes of breast cancer with DESI-MSI. Regions of interest were identified, including invasive breast cancer (IBC), ductal carcinoma in situ (DCIS), and adjacent benign tissue (ABT), and metabolomic profiles at 200 μm elaborated using Biomap software and the Lasso method. Top ions identified in IBC regions included polyunsaturated fatty acids, deprotonated glycerophospholipids, and sphingolipids. Highly saturated lipids, as well as antioxidant molecules [taurine (m/z 124.0068), uric acid (m/z 167.0210), ascorbic acid (m/z 175.0241), and glutathione (m/z 306.0765)], were able to distinguish IBC from ABT. Moreover, luminal B and triple-negative subtypes showed more complex lipid profiles compared with luminal A and HER2 subtypes. DCIS and IBC were distinguished on the basis of cell signaling and apoptosis-related ions [fatty acids (341.2100 and 382.3736 m/z) and glycerophospholipids (PE (P-16:0/22:6, m/z 746.5099, and PS (38:3), m/z 812.5440)]. In summary, DESI-MSI identified distinct lipid composition between DCIS and IBC and across molecular subtypes of breast cancer, with potential implications for breast cancer pathogenesis. Significance: These findings present the first in situ metabolomic findings of the four molecular subtypes of breast cancer, DCIS, and normal tissue, and add to the understanding of their pathogenesis.

中文翻译：

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乳腺癌分子亚型和前体病变的原位DESI-MSI血脂谱

已经建立了用于乳腺癌分类的临床上有意义的分子亚型，但是，对这些亚型的起始和进展仍知之甚少。解吸电喷雾电离质谱成像（DESI-MSI）的最新发展促进了分析化学与传统病理学的融合，从而允许对冷冻样品进行最少的组织预处理而进行化学分析。在这里，我们用DESI-MSI表征了乳腺癌分子亚型的化学组成。确定了感兴趣的区域，包括浸润性乳腺癌（IBC），原位导管癌（DCIS）和邻近的良性组织（ABT），以及使用Biomap软件和Lasso方法制作的200μm代谢组学谱。在IBC区域发现的主要离子包括多不饱和脂肪酸，去质子化的甘油磷脂和鞘脂。高度饱和的脂质以及抗氧化剂分子[牛磺酸（m / z 124.0068），尿酸（m / z 167.0210），抗坏血酸（m / z 175.0241）和谷胱甘肽（m / z 306.0765）]能够区分来自ABT的IBC。此外，与腔A和HER2亚型相比，腔B和三阴性亚型表现出更复杂的脂质分布。DCIS和IBC是根据细胞信号传导和凋亡相关离子[脂肪酸（341.2100和382.3736 m / z）和甘油磷脂（PE（P-16：0/22：6，m / z 746.5099和PS（ 38：3），m / z 812.5440）]。总之，DESI-MSI在DCIS和IBC之间以及乳腺癌的分子亚型之间鉴定出不同的脂质成分，这可能对乳腺癌的发病机理有潜在的影响。