title: Lipidomic Profiling of Lung Pleural Effusion Identifies Unique Metabotype for EGFR Mutants in Non-Small Cell Lung Cancer.
abstract: Cytology and histology forms the cornerstone for the diagnosis of non-small cell lung cancer (NSCLC) but obtaining sufficient tumour cells or tissue biopsies for these tests remains a challenge. We investigate the lipidome of lung pleural effusion (PE) for unique metabolic signatures to discriminate benign versus malignant PE and EGFR versus non-EGFR malignant subgroups to identify novel diagnostic markers that is independent of tumour cell availability. Using liquid chromatography mass spectrometry, we profiled the lipidomes of the PE of 30 benign and 41 malignant cases with or without EGFR mutation. Unsupervised principal component analysis revealed distinctive differences between the lipidomes of benign and malignant PE as well as between EGFR mutants and non-EGFR mutants. Docosapentaenoic acid and Docosahexaenoic acid gave superior sensitivity and specificity for detecting NSCLC when used singly. Additionally, several 20- and 22- carbon polyunsaturated fatty acids and phospholipid species were significantly elevated in the EGFR mutants compared to non-EGFR mutants. A 7-lipid panel showed great promise in the stratification of EGFR from non-EGFR malignant PE. Our data revealed novel lipid candidate markers in the non-cellular fraction of PE that holds potential to aid the diagnosis of benign, EGFR mutation positive and negative NSCLC.
authors.affiliation: Bioprocessing Technology Institute Agency for Science, Technology and Research (A*STAR), 20 Biopolis Way, #06-01 Centros, Singapore 138668, Singapore.
authors.forename: Ying Swan
authors.initials: YS
authors.lastname: Ho
authors.affiliation: Bioprocessing Technology Institute Agency for Science, Technology and Research (A*STAR), 20 Biopolis Way, #06-01 Centros, Singapore 138668, Singapore.
authors.forename: Lian Yee
authors.initials: LY
authors.lastname: Yip
authors.affiliation: Bioprocessing Technology Institute Agency for Science, Technology and Research (A*STAR), 20 Biopolis Way, #06-01 Centros, Singapore 138668, Singapore.
authors.forename: Nurhidayah
authors.initials: N
authors.lastname: Basri
authors.affiliation: Bioprocessing Technology Institute Agency for Science, Technology and Research (A*STAR), 20 Biopolis Way, #06-01 Centros, Singapore 138668, Singapore.
authors.forename: Vivian Su Hui
authors.initials: VS
authors.lastname: Chong
authors.affiliation: Bioprocessing Technology Institute Agency for Science, Technology and Research (A*STAR), 20 Biopolis Way, #06-01 Centros, Singapore 138668, Singapore.
authors.forename: Chin Chye
authors.initials: CC
authors.lastname: Teo
authors.affiliation: Bioprocessing Technology Institute Agency for Science, Technology and Research (A*STAR), 20 Biopolis Way, #06-01 Centros, Singapore 138668, Singapore.
authors.forename: Eddy
authors.initials: E
authors.lastname: Tan
authors.affiliation: Department of Pathology Singapore General Hospital 20 College Road, Academia, Level 10, Singapore 169856, Singapore.
authors.forename: Kah Ling
authors.initials: KL
authors.lastname: Lim
authors.affiliation: Department of Pathology Singapore General Hospital 20 College Road, Academia, Level 10, Singapore 169856, Singapore.
authors.forename: Gek San
authors.initials: GS
authors.lastname: Tan
authors.affiliation: Institute of High Performance Computing, Agency for Science, Technology and Research (A*STAR), 1 Fusionopolis way, #16-16 Connexis, Singapore 138632, Singapore.
authors.forename: Xulei
authors.initials: X
authors.lastname: Yang
authors.affiliation: Institute of High Performance Computing, Agency for Science, Technology and Research (A*STAR), 1 Fusionopolis way, #16-16 Connexis, Singapore 138632, Singapore.
authors.forename: Si Yong
authors.initials: SY
authors.lastname: Yeo
authors.affiliation: Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Outram Rd, Singapore 169608.
authors.forename: Mariko Si Yue
authors.initials: MS
authors.lastname: Koh
authors.affiliation: Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Outram Rd, Singapore 169608.
authors.forename: Anantham
authors.initials: A
authors.lastname: Devanand
authors.affiliation: Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Outram Rd, Singapore 169608.
authors.forename: Angela
authors.initials: A
authors.lastname: Takano
authors.affiliation: National Cancer Centre, 11 Hospital Drive, Singapore 169610, Singapore.
authors.forename: Eng Huat
authors.initials: EH
authors.lastname: Tan
authors.affiliation: National Cancer Centre, 11 Hospital Drive, Singapore 169610, Singapore.|Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), 20 Biopolis Way, #06-01 Centros, Singapore 138668, Singapore.
authors.forename: Daniel Shao Weng
authors.initials: DS
authors.lastname: Tan
authors.affiliation: Department of Pathology Singapore General Hospital 20 College Road, Academia, Level 10, Singapore 169856, Singapore.|Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), 20 Biopolis Way, #06-01 Centros, Singapore 138668, Singapore.
authors.forename: Tony Kiat Hon
authors.initials: TK
authors.lastname: Lim
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D002853:Chromatography, Liquid; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D008055:Lipids / Q000032:analysis*; D008297:Male; D013058:Mass Spectrometry; D055432:Metabolomics; D008875:Middle Aged; D050505:Mutant Proteins / Q000235:genetics*; D010996:Pleural Effusion / Q000473:pathology*
chemical_list: D015415:Biomarkers; D008055:Lipids; D050505:Mutant Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors