Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Department of Anatomy and Cell Biology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan.
BMC Cancer. 2021 Mar 10;21(1):262. doi: 10.1186/s12885-021-08001-5.
Probe electrospray ionization-mass spectrometry (PESI-MS) can rapidly visualize mass spectra of small, surgically obtained tissue samples, and is a promising novel diagnostic tool when combined with machine learning which discriminates malignant spectrum patterns from others. The present study was performed to evaluate the utility of this device for rapid diagnosis of colorectal liver metastasis (CRLM).
A prospectively planned study using retrospectively obtained tissues was performed. In total, 103 CRLM samples and 80 non-cancer liver tissues cut from surgically extracted specimens were analyzed using PESI-MS. Mass spectra obtained by PESI-MS were classified into cancer or non-cancer groups by using logistic regression, a kind of machine learning. Next, to identify the exact molecules responsible for the difference between CRLM and non-cancerous tissues, we performed liquid chromatography-electrospray ionization-MS (LC-ESI-MS), which visualizes sample molecular composition in more detail.
This diagnostic system distinguished CRLM from non-cancer liver parenchyma with an accuracy rate of 99.5%. The area under the receiver operating characteristic curve reached 0.9999. LC-ESI-MS analysis showed higher ion intensities of phosphatidylcholine and phosphatidylethanolamine in CRLM than in non-cancer liver parenchyma (P < 0.01, respectively). The proportion of phospholipids categorized as monounsaturated fatty acids was higher in CRLM (37.2%) than in non-cancer liver parenchyma (10.7%; P < 0.01).
The combination of PESI-MS and machine learning distinguished CRLM from non-cancer tissue with high accuracy. Phospholipids categorized as monounsaturated fatty acids contributed to the difference between CRLM and normal parenchyma and might also be a useful diagnostic biomarker and therapeutic target for CRLM.
探针电喷雾电离-质谱（PESI-MS）可以快速可视化小的手术获得的组织样本的质谱，并且当与机器学习结合使用时，当区分恶性谱模式与其他模式时，是一种很有前途的新型诊断工具。本研究旨在评估该设备在快速诊断结直肠癌肝转移（CRLM）中的效用。
使用回顾性获得的组织进行了一项前瞻性计划的研究。总共分析了 103 个 CRLM 样本和 80 个从手术切除标本中切下的非癌性肝脏组织。使用 PESI-MS 获得的质谱通过逻辑回归（一种机器学习）分类为癌症或非癌症组。接下来，为了确定导致 CRLM 与非癌组织之间差异的确切分子，我们进行了液相色谱-电喷雾电离-MS（LC-ESI-MS），它可以更详细地可视化样品分子组成。
该诊断系统以 99.5%的准确率将 CRLM 与非癌性肝实质区分开来。接收者操作特征曲线下的面积达到 0.9999。LC-ESI-MS 分析显示，CRLM 中的磷脂酰胆碱和磷脂酰乙醇胺的离子强度高于非癌性肝实质（分别为 P<0.01）。CRLM 中的单不饱和脂肪酸分类的磷脂比例（37.2%）高于非癌性肝实质（10.7%；P<0.01）。
PESI-MS 和机器学习的结合以高精度区分 CRLM 与非癌组织。分类为单不饱和脂肪酸的磷脂有助于 CRLM 与正常实质之间的差异，也可能是 CRLM 的有用诊断生物标志物和治疗靶标。
