title: Qualification and Verification of Serological Biomarker Candidates for Lung Adenocarcinoma by Targeted Mass Spectrometry.
abstract: Lung cancer is the leading cause of cancer mortality worldwide. Although many biomarkers have been identified for lung cancer, their low specificity and sensitivity present an urgent need for the identification of more candidate biomarkers. In this study, we conducted MRM-based targeted analysis to evaluate the potential utility of a list of candidate proteins for lung cancer diagnosis. A total of 1249 transitions of 420 peptides representing 102 candidate proteins from our previous study and the literature were first screened by MRM analysis in pooled plasma samples, resulting in 78 proteins remaining in the list. Relative quantification of these 78 proteins was further performed in 60 individual plasma samples from lung adenocarcinoma patients in stages I-III and matched healthy control subjects. Ultimately, nine proteins were found to be able to distinguish patients from controls. Further combinations of five, three, and two candidate marker proteins improved the sensitivity to discriminate patients from controls and resulted in a merged AUC value of nearly 1.00 in stages I-III patients versus controls. Our results highlighted several possible markers for lung adenocarcinoma, and the proposed protein panels require further validation in a larger cohort to evaluate their potential use in clinical applications or development of therapeutics.
authors.affiliation: †Institute of Chemistry, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Hsin-Yi
authors.initials: HY
authors.lastname: Wu
authors.affiliation: ‡Division of Thoracic Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan.
authors.forename: Yih-Gang
authors.initials: YG
authors.lastname: Goan
authors.affiliation: §Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin 53705, United States.|∥Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan 70428, Taiwan.
authors.forename: Ying-Hua
authors.initials: YH
authors.lastname: Chang
authors.affiliation: ∥Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan 70428, Taiwan.
authors.forename: Yi-Fang
authors.initials: YF
authors.lastname: Yang
authors.affiliation: ∥Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan 70428, Taiwan.
authors.forename: Hsiao-Jen
authors.initials: HJ
authors.lastname: Chang
authors.affiliation: ⊥Department of Internal Medicine, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan 70101, Taiwan.
authors.forename: Pin-Nan
authors.initials: PN
authors.lastname: Cheng
authors.affiliation: ∥Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan 70428, Taiwan.
authors.forename: Chih-Chieh
authors.initials: CC
authors.lastname: Wu
authors.affiliation: #Institute of Biomedical Chemistry, 119121 Moscow, Russia.
authors.forename: Victor G
authors.initials: VG
authors.lastname: Zgoda
authors.affiliation: †Institute of Chemistry, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Yu-Ju
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: ∥Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan 70428, Taiwan.
authors.forename: Pao-Chi
authors.initials: PC
authors.lastname: Liao
mesh_terms: D000230:Adenocarcinoma / Q000097:blood* / Q000175:diagnosis / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D014408:Biomarkers, Tumor / Q000097:blood* / Q000378:metabolism; D001798:Blood Proteins / Q000032:analysis / Q000378:metabolism; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D010455:Peptides / Q000097:blood* / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D001798:Blood Proteins; D010455:Peptides
keywords: Multiple reaction monitoring (MRM); biomarkers; lung adenocarcinoma; multimarker panel; plasma