title: In situ biomarker discovery and label-free molecular histopathological diagnosis of lung cancer by ambient mass spectrometry imaging.
abstract: Sensitive and spatial exploration of the metabolism of tumors at the metabolome level is highly challenging. In this study, we developed an in situ metabolomics method based on ambient mass spectrometry imaging using air flow-assisted desorption electrospray ionization (AFADESI), which can spatially explore the alteration of global metabolites in tissues with high sensitivity. Using this method, we discovered potential histopathological diagnosis biomarkers (including lipids, amino acids, choline, peptides, and carnitine) from 52 postoperative lung cancer tissue samples and then subsequently used these biomarkers to generate images for rapid and label-free histopathological diagnosis. These biomarkers were validated with a sensitivity and a specificity of 93.5% and 100%, respectively. Moreover, a single imaging analysis of a cryosection that visualized all these biomarkers, taking tens of minutes, revealed the type and subtype of the cancer. This method could potentially be used as a molecular pathological tool for rapid clinical lung cancer diagnosis and immediate image-guided surgery.
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, P. R. China.
authors.forename: Tiegang
authors.initials: T
authors.lastname: Li
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, P. R. China.
authors.forename: Jiuming
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, P. R. China.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Mao
authors.affiliation: State Key Laboratory of Precision Measurement Technology and Instruments, Department of Precision Instruments, Tsinghua University, Beijing 100084, P. R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Bi
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, P. R. China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Precision Measurement Technology and Instruments, Department of Precision Instruments, Tsinghua University, Beijing 100084, P. R. China.
authors.forename: Chengan
authors.initials: C
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Precision Measurement Technology and Instruments, Department of Precision Instruments, Tsinghua University, Beijing 100084, P. R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P. R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Precision Measurement Technology and Instruments, Department of Precision Instruments, Tsinghua University, Beijing 100084, P. R. China.
authors.forename: Xiaohao
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P. R. China.
authors.forename: Mingrong
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, P. R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, P. R. China.
authors.forename: Zeper
authors.initials: Z
authors.lastname: Abliz
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D013058:Mass Spectrometry / Q000379:methods; D055442:Metabolome; D055432:Metabolomics / Q000379:methods; D008856:Microscopy, Fluorescence; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor