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Profiling of Serum Metabolites Using MALDI-TOF and Triple-TOF Mass Spectrometry to Develop a Screen for Ovarian Cancer
Jun Hwa Lee, Yun Hwan Kim, Kyung-Hee Kim, Jae Youl Cho, Sang Myung Woo, Byong Chul Yoo, Seung Cheol Kim
Cancer Res Treat. 2018;50(3):883-893.   Published online September 18, 2017
DOI: https://doi.org/10.4143/crt.2017.275
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
We sought to develop a matrix assisted laser desorption ionization-time of flight (MALDI-TOF)-based, ovarian cancer (OVC), low-mass-ion discriminant equation (LOME) and to evaluate a possible supportive role for triple-TOF mass analysis in identifying metabolic biomarkers.
Materials and Methods
A total of 114 serum samples from patients with OVC and benign ovarian tumors were subjected to MALDI-TOF analysis and a total of 137 serum samples from healthy female individuals and patients with OVC, colorectal cancer, hepatobiliary cancer, and pancreatic cancer were subjected to triple-TOF analysis. An OVC LOME was constructed by reference to the peak intensity ratios of discriminatory low-mass ion (LMI) pairs. Triple-TOF analysiswas used to select and identify metabolic biomarkers for OVC screening.
Results
Three OVC LOMEs were finally constructed using discriminatory LMI pairs (137.1690 and 84.4119 m/z; 496.5022 and 709.7642 m/z; and 524.5614 and 709.7642 m/z); all afforded accuracies of > 90%. The LMIs at 496.5022 m/z and 524.5614 m/z were those of lysophosphatidylcholine (LPC) 16:0 and LPC 18:0. Triple-TOF analysis selected seven discriminative LMIs; each LMI had a specificity > 90%. Of the seven LMIs, fourwith a 137.0455 m/z ion atretention times of 2.04-3.14 minuteswere upregulated in sera from OVC patients; the ion was identified as that derived from hypoxanthine.
Conclusion
MALDI-TOF–based OVC LOMEs combined with triple-TOF–based OVC metabolic biomarkers allow reliable OVC screening; the techniques are mutually complementary both quantitatively and qualitatively.

Citations

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  • Detection of Protein and Metabolites in Cancer Analyses by MALDI 2000–2025
    Dorota Bartusik-Aebisher, Daniel Roshan Justin Raj, David Aebisher
    Cancers.2025; 17(21): 3524.     CrossRef
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    Andrea Jiménez-Franco, Juan Manuel Jiménez-Aguilar, Marta Canela-Capdevila, Raquel García-Pablo, Helena Castañé, Cristian Martínez-Navidad, Pablo Araguas, Bárbara Malavé, Rocío Benavides-Villarreal, Johana C. Acosta, Alina Iuliana Onoiu, Navita Somaiah, J
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    Molecules.2022; 27(19): 6196.     CrossRef
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    Nanomaterials.2021; 11(9): 2432.     CrossRef
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  • Performance of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) in diagnosis of ovarian cancer: a systematic review and meta-analysis
    Kexin Li, Yuqing Pei, Yue Wu, Yi Guo, Wei Cui
    Journal of Ovarian Research.2020;[Epub]     CrossRef
  • Comparative cerebrospinal fluid metabolites profiling in glioma patients to predict malignant transformation and leptomeningeal metastasis with a potential for preventive personalized medicine
    Ji Hye Im, Byong Chul Yoo, Jun Hwa Lee, Kyung-Hee Kim, Tae Hoon Kim, Kyue-Yim Lee, Jong Heon Kim, Jong Bae Park, Ji-Woong Kwon, Sang Hoon Shin, Heon Yoo, Ho-Shin Gwak
    EPMA Journal.2020; 11(3): 469.     CrossRef
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    Mingfeng Xiang, Feng Du, Jing Dai, Ling Chen, Ruijin Geng, Huiming Huang, Baogang Xie
    Biomarkers in Medicine.2020; 14(8): 675.     CrossRef
  • Metabolomic Biomarkers in Gynecology: A Treasure Path or a False Path?
    Igor Govorov , Stanislav Sitkin , Tatyana Pervunina , Alexey Moskvin , Denis Baranenko , Eduard Komlichenko
    Current Medicinal Chemistry.2020; 27(22): 3611.     CrossRef
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Identification of Hypoxanthine and Phosphoenolpyruvic Acid as Serum Markers of Chemoradiotherapy Response in Locally Advanced Rectal Cancer
Kun Kim, Seung-Gu Yeo, Byong Chul Yoo
Cancer Res Treat. 2015;47(1):78-89.   Published online August 21, 2014
DOI: https://doi.org/10.4143/crt.2013.127
AbstractAbstract PDFPubReaderePub
Purpose
Patients show variable responses to chemoradiotherapy (CRT), which is generally administered before surgery for locally advanced rectal cancer (LARC). The aim of this study was to identify molecular markers predictive of CRT responses by analysis of low-mass ions (LMIs) in serum of LARC patients. Materials and Methods LMIs (< 1,000 m/z) in serum obtained before CRT from 73 LARC (cT3-4) patients were profiled using matrix-assisted laser desorption/ionization mass spectrometry. LMIs with higher weighting factors in discriminating CRT responses were selected using principal components analysis and discriminant analysis. Selected LMIs were identified using the Human Metabolome Database. The concentrations of identified LMIs were determined by colorimetric enzyme assay, and compared according to post-CRT pathological stage (ypStage) or Dworak’s tumor regression grade (TRG). Results The nine highest-ranking LMIs were selected. Among them, two LMIs with 137.08 and 169.04 m/z were identified as hypoxanthine (HX) and phosphoenolpyruvic acid (PEP), respectively. Higher HX concentration was observed in patients with ypStage 0-1 compared to ypStage 2-4 (p=0.034) or ypStage 3-4 (p=0.030); a similar difference was observed between TRG 4-3 and TRG 1 (p=0.035). HX > 16.0 μM showed significant association with ypStage 0-1 or TRG 4-3 than ypStage 3-4 (p=0.009) or TRG 1 (p=0.024), respectively. In contrast, a significantly lower concentration of PEP was observed in TRG 4-3 compared with TRG 2-1 (p=0.012). Conclusion Findings of this study demonstrated that serum concentrations of HX and PEP, identified using LMI profiling, may be useful for predicting the CRT response of LARC patients before treatment.

Citations

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    Cancer Research and Treatment.2018; 50(3): 883.     CrossRef
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    Byong Chul Yoo, Seung-Gu Yeo
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  • Reduced levels of N’-methyl-2-pyridone-5-carboxamide and lysophosphatidylcholine 16:0 in the serum of patients with intrahepatic cholangiocarcinoma, and the correlation with recurrence-free survival
    Kyung-Hee Kim, Jungnam Joo, Boram Park, Sang-Jae Park, Woo Jin Lee, Sung-Sik Han, Tae Hyun Kim, Eun Kyung Hong, Sang Myung Woo, Byong Chul Yoo
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  • Seven low-mass ions in pretreatment serum as potential predictive markers of the chemoradiotherapy response of rectal cancer
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  • 14,275 View
  • 88 Download
  • 26 Web of Science
  • 26 Crossref
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