Chiangjong Wararat, Bhakdi Sebastian Chakrit, Woramongkolchai Noppawan, Vanichapol Thitinee, Pongsakul Nutkridta, Hongeng Suradej, Chutipongtanate Somchai
Pediatric Translational Research Unit, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand.
Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
Cancers (Basel). 2021 Jul 27;13(15):3775. doi: 10.3390/cancers13153775.
Circulating atypical cells (CAC) are released from a primary tumour site into peripheral blood and are indicators of cancer metastasis. CAC occur at very low frequency in circulating blood, and their detection remains challenging. Moreover, white blood cells (WBC) are the major contaminant in enriched CAC samples. Here, we developed matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) as a novel CAC characterization platform. Main spectra profiles (MSP) of normal and cancer cells were generated by MALDI-TOF MS, and a cell-main spectra database was then compiled and analysed using the MALDI Biotyper software. Logarithmic scores accurately predicted distinct cell types. The feasibility of this workflow was then validated using simulated samples, which were prepared by 5000 WBC of three healthy individuals spiked with varying numbers (3, 6, 12, 25, 50, and 100) of lung, colon, or prostate cancer cells. MALDI-TOF MS was able to detect cancer cells down to six cells over the background noise of 5000 WBC with significantly higher predictive scores as compared to WBC alone. Further development of cell-MSP database to cover all cancer types sourced from cell lines and patient tumours may enable the use of MALDI-TOF MS as a cancer-screening platform in clinical settings in the future.
循环中的非典型细胞（CAC）从原发性肿瘤部位释放到外周血中，是癌症转移的指标。CAC在循环血液中出现的频率极低，其检测仍然具有挑战性。此外，白细胞（WBC）是富集的CAC样本中的主要污染物。在此，我们开发了基质辅助激光解吸电离飞行时间质谱（MALDI-TOF MS）作为一种新型的CAC表征平台。通过MALDI-TOF MS生成正常细胞和癌细胞的主要光谱图谱（MSP），然后使用MALDI Biotyper软件编译并分析细胞主要光谱数据库。对数分数准确地预测了不同的细胞类型。然后使用模拟样本验证了该工作流程的可行性，模拟样本由三名健康个体的5000个白细胞添加不同数量（3、6、12、25、50和100）的肺癌、结肠癌或前列腺癌细胞制备而成。与仅检测白细胞相比，MALDI-TOF MS能够在5000个白细胞的背景噪声下检测到低至六个癌细胞，且预测分数显著更高。进一步开发涵盖源自细胞系和患者肿瘤的所有癌症类型的细胞MSP数据库，可能使MALDI-TOF MS在未来临床环境中用作癌症筛查平台。
