#METABOLOMICS WORKBENCH siriphan_man_20250909_010522 DATATRACK_ID:6402 STUDY_ID:ST004184 ANALYSIS_ID:AN006947 PROJECT_ID:PR002474
VERSION             	1
CREATED_ON             	September 9, 2025, 10:45 pm
#PROJECT
PR:PROJECT_TITLE                 	Plasma Metabolomic Analysis in Thai EGFR-mutated Non-Small Cell Lung Cancer
PR:PROJECT_TITLE                 	Patients
PR:PROJECT_SUMMARY               	Lung cancer remains the leading cause of cancer-related deaths worldwide,
PR:PROJECT_SUMMARY               	emphasizing an urgent need for effective, non-invasive diagnostic and prognostic
PR:PROJECT_SUMMARY               	biomarkers. Metabolic reprogramming driven by oncogenic driver alterations,
PR:PROJECT_SUMMARY               	especially EGFR mutations in non-small cell lung cancer (NSCLC), provides
PR:PROJECT_SUMMARY               	promising metabolic signatures detectable in plasma. This study aimed to
PR:PROJECT_SUMMARY               	identify plasma metabolomic biomarkers distinguishing healthy individuals from
PR:PROJECT_SUMMARY               	NSCLC patients and to further stratify NSCLC patients by EGFR mutation status
PR:PROJECT_SUMMARY               	and EGFR tyrosine kinase inhibitor (TKI) resistance. Using gas
PR:PROJECT_SUMMARY               	chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass
PR:PROJECT_SUMMARY               	spectrometry (LC-MS/MS), we quantified four groups of targeted metabolites
PR:PROJECT_SUMMARY               	(amino acids, organic acids, sugar and sugar alcohols, and phospholipids) of 78
PR:PROJECT_SUMMARY               	individuals, including NSCLC patients and healthy controls. Metabolomic
PR:PROJECT_SUMMARY               	signatures distinctly separated healthy controls from NSCLC patients and,
PR:PROJECT_SUMMARY               	furthermore, EGFR-mutated NSCLC from EGFR wild-type cases. Additionally,
PR:PROJECT_SUMMARY               	metabolomics results effectively distinguished EGFR TKI-resistant from
PR:PROJECT_SUMMARY               	treatment-naïve EGFR-mutated NSCLC. Our findings highlight the potential of
PR:PROJECT_SUMMARY               	plasma metabolites as minimally invasive biomarkers for molecular classification
PR:PROJECT_SUMMARY               	and monitoring therapeutic response in NSCLC patients.
PR:INSTITUTE                     	Mahidol University
PR:LAST_NAME                     	Khoomrung
PR:FIRST_NAME                    	Sakda
PR:ADDRESS                       	2 Wanglang road, Bangkok noi, bangkok, 10700, Thailand
PR:EMAIL                         	Sakda.kho@mahidol.edu
PR:PHONE                         	6624195505
#STUDY
ST:STUDY_TITLE                   	Plasma Sugar and Sugar Alcohols Analysis in Thai EGFR-mutated Non-Small Cell
ST:STUDY_TITLE                   	Lung Cancer Patients
ST:STUDY_SUMMARY                 	Lung cancer remains the leading cause of cancer-related deaths worldwide,
ST:STUDY_SUMMARY                 	emphasizing an urgent need for effective, non-invasive diagnostic and prognostic
ST:STUDY_SUMMARY                 	biomarkers. Metabolic reprogramming driven by oncogenic driver alterations,
ST:STUDY_SUMMARY                 	especially EGFR mutations in non-small cell lung cancer (NSCLC), provides
ST:STUDY_SUMMARY                 	promising metabolic signatures detectable in plasma. This study aimed to
ST:STUDY_SUMMARY                 	identify plasma metabolomic biomarkers distinguishing healthy individuals from
ST:STUDY_SUMMARY                 	NSCLC patients and to further stratify NSCLC patients by EGFR mutation status
ST:STUDY_SUMMARY                 	and EGFR tyrosine kinase inhibitor (TKI) resistance. Using gas
ST:STUDY_SUMMARY                 	chromatography-mass spectrometry (GC-MS), we quantified 18 sugar and sugar
ST:STUDY_SUMMARY                 	alcohols of 78 individuals, including NSCLC patients and healthy controls.
ST:INSTITUTE                     	Mahidol University
ST:LAST_NAME                     	Khoomrung
ST:FIRST_NAME                    	Sakda
ST:ADDRESS                       	2 Wanglang road, Bangkok noi, bangkok, 10700, Thailand
ST:EMAIL                         	Sakda.kho@mahidol.edu
ST:PHONE                         	6624195505
#SUBJECT
SU:SUBJECT_TYPE                  	Human
SU:SUBJECT_SPECIES               	Homo sapiens
SU:TAXONOMY_ID                   	9606
#SUBJECT_SAMPLE_FACTORS:         	SUBJECT(optional)[tab]SAMPLE[tab]FACTORS(NAME:VALUE pairs separated by |)[tab]Raw file names and additional sample data
SUBJECT_SAMPLE_FACTORS           	-	A01	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=A01.mzML
SUBJECT_SAMPLE_FACTORS           	-	A02	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=A02.mzML
SUBJECT_SAMPLE_FACTORS           	-	A13	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=A13.mzML
SUBJECT_SAMPLE_FACTORS           	-	A14	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=A14.mzML
SUBJECT_SAMPLE_FACTORS           	-	A20	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=A20.mzML
SUBJECT_SAMPLE_FACTORS           	-	A22	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=A22.mzML
SUBJECT_SAMPLE_FACTORS           	-	A23	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=A23.mzML
SUBJECT_SAMPLE_FACTORS           	-	A24	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=A24.mzML
SUBJECT_SAMPLE_FACTORS           	-	A25	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=A25.mzML
SUBJECT_SAMPLE_FACTORS           	-	A26	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=A26.mzML
SUBJECT_SAMPLE_FACTORS           	-	A27	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=A27.mzML
SUBJECT_SAMPLE_FACTORS           	-	A28	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=A28.mzML
SUBJECT_SAMPLE_FACTORS           	-	A29	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=A29.mzML
SUBJECT_SAMPLE_FACTORS           	-	A30	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=A30.mzML
SUBJECT_SAMPLE_FACTORS           	-	A31	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=A31.mzML
SUBJECT_SAMPLE_FACTORS           	-	A32	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=A32.mzML
SUBJECT_SAMPLE_FACTORS           	-	A33	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=A33.mzML
SUBJECT_SAMPLE_FACTORS           	-	A34	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=A34.mzML
SUBJECT_SAMPLE_FACTORS           	-	A35	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=A35.mzML
SUBJECT_SAMPLE_FACTORS           	-	A36	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=A36.mzML
SUBJECT_SAMPLE_FACTORS           	-	A37	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=A37.mzML
SUBJECT_SAMPLE_FACTORS           	-	A38	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=A38.mzML
SUBJECT_SAMPLE_FACTORS           	-	A39	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=A39.mzML
SUBJECT_SAMPLE_FACTORS           	-	A40	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=A40.mzML
SUBJECT_SAMPLE_FACTORS           	-	A41	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=A41.mzML
SUBJECT_SAMPLE_FACTORS           	-	A42	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=A42.mzML
SUBJECT_SAMPLE_FACTORS           	-	A43	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=A43.mzML
SUBJECT_SAMPLE_FACTORS           	-	A45	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=A45.mzML
SUBJECT_SAMPLE_FACTORS           	-	A46	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=A46.mzML
SUBJECT_SAMPLE_FACTORS           	-	B01	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=B01.mzML
SUBJECT_SAMPLE_FACTORS           	-	B02	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=B02.mzML
SUBJECT_SAMPLE_FACTORS           	-	B05	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=B05.mzML
SUBJECT_SAMPLE_FACTORS           	-	B06	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=B06.mzML
SUBJECT_SAMPLE_FACTORS           	-	B07	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=B07.mzML
SUBJECT_SAMPLE_FACTORS           	-	B08	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=B08.mzML
SUBJECT_SAMPLE_FACTORS           	-	B09	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=B09.mzML
SUBJECT_SAMPLE_FACTORS           	-	B10	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=B10.mzML
SUBJECT_SAMPLE_FACTORS           	-	B11	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=B11.mzML
SUBJECT_SAMPLE_FACTORS           	-	B12	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=B12.mzML
SUBJECT_SAMPLE_FACTORS           	-	B13	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=B13.mzML
SUBJECT_SAMPLE_FACTORS           	-	B14	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=B14.mzML
SUBJECT_SAMPLE_FACTORS           	-	B15	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=B15.mzML
SUBJECT_SAMPLE_FACTORS           	-	B16	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=B16.mzML
SUBJECT_SAMPLE_FACTORS           	-	B17	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=B17.mzML
SUBJECT_SAMPLE_FACTORS           	-	B18	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=B18.mzML
SUBJECT_SAMPLE_FACTORS           	-	B19	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=B19.mzML
SUBJECT_SAMPLE_FACTORS           	-	B21	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=B21.mzML
SUBJECT_SAMPLE_FACTORS           	-	B22	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=B22.mzML
SUBJECT_SAMPLE_FACTORS           	-	B23	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=B23.mzML
SUBJECT_SAMPLE_FACTORS           	-	B24	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=B24.mzML
SUBJECT_SAMPLE_FACTORS           	-	B25	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=B25.mzML
SUBJECT_SAMPLE_FACTORS           	-	B26	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=B26.mzML
SUBJECT_SAMPLE_FACTORS           	-	B27	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=B27.mzML
SUBJECT_SAMPLE_FACTORS           	-	B28	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=B28.mzML
SUBJECT_SAMPLE_FACTORS           	-	B30	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=B30.mzML
SUBJECT_SAMPLE_FACTORS           	-	B33	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=B33.mzML
SUBJECT_SAMPLE_FACTORS           	-	B34	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=B34.mzML
SUBJECT_SAMPLE_FACTORS           	-	B42	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	RAW_FILE_NAME(Sugar mzML file)=B42.mzML
SUBJECT_SAMPLE_FACTORS           	-	C01	Sample source:Plasma | Disease:Healthy | EGFR mutation:n/a | Treatment:n/a	RAW_FILE_NAME(Sugar mzML file)=C01-re.mzML
SUBJECT_SAMPLE_FACTORS           	-	C02	Sample source:Plasma | Disease:Healthy | EGFR mutation:n/a | Treatment:n/a	RAW_FILE_NAME(Sugar mzML file)=C02.mzML
SUBJECT_SAMPLE_FACTORS           	-	C03	Sample source:Plasma | Disease:Healthy | EGFR mutation:n/a | Treatment:n/a	RAW_FILE_NAME(Sugar mzML file)=C03.mzML
SUBJECT_SAMPLE_FACTORS           	-	C04	Sample source:Plasma | Disease:Healthy | EGFR mutation:n/a | Treatment:n/a	RAW_FILE_NAME(Sugar mzML file)=C04.mzML
SUBJECT_SAMPLE_FACTORS           	-	C05	Sample source:Plasma | Disease:Healthy | EGFR mutation:n/a | Treatment:n/a	RAW_FILE_NAME(Sugar mzML file)=C05.mzML
SUBJECT_SAMPLE_FACTORS           	-	C06	Sample source:Plasma | Disease:Healthy | EGFR mutation:n/a | Treatment:n/a	RAW_FILE_NAME(Sugar mzML file)=C06.mzML
SUBJECT_SAMPLE_FACTORS           	-	C07	Sample source:Plasma | Disease:Healthy | EGFR mutation:n/a | Treatment:n/a	RAW_FILE_NAME(Sugar mzML file)=C07.mzML
SUBJECT_SAMPLE_FACTORS           	-	C08	Sample source:Plasma | Disease:Healthy | EGFR mutation:n/a | Treatment:n/a	RAW_FILE_NAME(Sugar mzML file)=C08.mzML
SUBJECT_SAMPLE_FACTORS           	-	C09	Sample source:Plasma | Disease:Healthy | EGFR mutation:n/a | Treatment:n/a	RAW_FILE_NAME(Sugar mzML file)=C09.mzML
SUBJECT_SAMPLE_FACTORS           	-	C10	Sample source:Plasma | Disease:Healthy | EGFR mutation:n/a | Treatment:n/a	RAW_FILE_NAME(Sugar mzML file)=C10.mzML
SUBJECT_SAMPLE_FACTORS           	-	D01	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:TKI resistant	RAW_FILE_NAME(Sugar mzML file)=D01.mzML
SUBJECT_SAMPLE_FACTORS           	-	D02	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:TKI resistant	RAW_FILE_NAME(Sugar mzML file)=D02.mzML
SUBJECT_SAMPLE_FACTORS           	-	D03	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:TKI resistant	RAW_FILE_NAME(Sugar mzML file)=D03.mzML
SUBJECT_SAMPLE_FACTORS           	-	D04	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:TKI resistant	RAW_FILE_NAME(Sugar mzML file)=D04.mzML
SUBJECT_SAMPLE_FACTORS           	-	D05	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:TKI resistant	RAW_FILE_NAME(Sugar mzML file)=D05.mzML
SUBJECT_SAMPLE_FACTORS           	-	D06	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:TKI resistant	RAW_FILE_NAME(Sugar mzML file)=D06.mzML
SUBJECT_SAMPLE_FACTORS           	-	D08	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:TKI resistant	RAW_FILE_NAME(Sugar mzML file)=D08.mzML
SUBJECT_SAMPLE_FACTORS           	-	D09	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:TKI resistant	RAW_FILE_NAME(Sugar mzML file)=D09.mzML
SUBJECT_SAMPLE_FACTORS           	-	D10	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:TKI resistant	RAW_FILE_NAME(Sugar mzML file)=D10.mzML
SUBJECT_SAMPLE_FACTORS           	-	D11	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:TKI resistant	RAW_FILE_NAME(Sugar mzML file)=D11.mzML
#COLLECTION
CO:COLLECTION_SUMMARY            	Blood was drawn directly into Cell-Free DNA BCT® tubes to stabilize cell-free
CO:COLLECTION_SUMMARY            	DNA. Plasma was separated from cellular components by centrifugation. For NSCLC
CO:COLLECTION_SUMMARY            	patients, plasma was first subjected to EGFR mutation analysis. Plasma aliquots
CO:COLLECTION_SUMMARY            	from all participants were stored at −80°C until subsequent analysis.
CO:SAMPLE_TYPE                   	Blood (plasma)
#TREATMENT
TR:TREATMENT_SUMMARY             	Treatment-naïve NSCLC patients had never received any systemic treatment for
TR:TREATMENT_SUMMARY             	lung cancer. EGFR TKI-resistant NSCLC patients had evidence of disease
TR:TREATMENT_SUMMARY             	progression according to the Response Evaluation Criteria In Solid Tumors
TR:TREATMENT_SUMMARY             	(RECIST) version 1.1 after receiving first- or second-generation EGFR TKI
TR:TREATMENT_SUMMARY             	treatment. All EGFR TKI-resistant NSCLC patients had acquired EGFR T790M
TR:TREATMENT_SUMMARY             	mutation.
#SAMPLEPREP
SP:SAMPLEPREP_SUMMARY            	For sugar alcohol, 50 µL of plasma was extracted with 400 µL of methanol in a
SP:SAMPLEPREP_SUMMARY            	1.5 ml Eppendorf tube, vortexed at 2,200 rpm for 10 min (three times), then
SP:SAMPLEPREP_SUMMARY            	centrifuged at 10,000 x g for 10 min (4°C) using a centrifuge (5810R,
SP:SAMPLEPREP_SUMMARY            	Eppendorf, USA). A 100 µL of supernatant was transferred into a 2-ml GC glass
SP:SAMPLEPREP_SUMMARY            	vial, and 20 µL of 1µmol/mL of internal standard (myristic acid-D27) in hexane
SP:SAMPLEPREP_SUMMARY            	was added. The mixture was dried at 60°C for 2 hours using a vacuum
SP:SAMPLEPREP_SUMMARY            	concentrator (Concentrator plus, Eppendorf, USA), then added with 50 µl
SP:SAMPLEPREP_SUMMARY            	dichloromethane and dried again for 30 min. Subsequently, a 50 µL of 40 mg/mL
SP:SAMPLEPREP_SUMMARY            	of O-methyl hydroxylamine hydrochloride in pyridine was added to the dried
SP:SAMPLEPREP_SUMMARY            	sample for a methoxylation reaction. The reaction was performed under 30 °C for
SP:SAMPLEPREP_SUMMARY            	90 min. For trimethylsilylation reaction, a 50 µL of N-trimethyl-N-methyl
SP:SAMPLEPREP_SUMMARY            	trifluoroacetamide containing 1% of trimethylchlorosilane (MSTFA + 1% TMCS) was
SP:SAMPLEPREP_SUMMARY            	added into the mixtures and incubated at 37 °C for 30 min. The derivatized
SP:SAMPLEPREP_SUMMARY            	samples were cooled at room temperature and immediately for GC/MS analysis.
#CHROMATOGRAPHY
CH:CHROMATOGRAPHY_SUMMARY        	The sample was analyzed by a gas chromatography-quadrupole time of flight mass
CH:CHROMATOGRAPHY_SUMMARY        	spectrometer (GC/Q-TOF, GC 7890B/MSD 7250, Agilent Technologies, USA) coupled to
CH:CHROMATOGRAPHY_SUMMARY        	the PAL autosampler system (CTC Analytics AG, Switzerland). An aliquot of 2 µl
CH:CHROMATOGRAPHY_SUMMARY        	was injected into GC/Q-TOFMS using split mode with an injector temperature of
CH:CHROMATOGRAPHY_SUMMARY        	250°C, a split ratio of 10 to 1, and a DB-5MS UI column (30 m, 0.25 mm i.d.,
CH:CHROMATOGRAPHY_SUMMARY        	Agilent Technologies, USA). Helium was used as a carrier gas with a constant
CH:CHROMATOGRAPHY_SUMMARY        	flow rate of 1.0 ml/min. The GC oven was programmed as follows: The initial oven
CH:CHROMATOGRAPHY_SUMMARY        	temperature was controlled at 60°C, help for 1 min. Then, the temperature was
CH:CHROMATOGRAPHY_SUMMARY        	ramped from 60 °C to 325 °C at the rate of 10 °C/min and held for 10 min. The
CH:CHROMATOGRAPHY_SUMMARY        	total run time was 37.5 min. The transfer line, ion source, and quadrupole were
CH:CHROMATOGRAPHY_SUMMARY        	set as 325 °C, 240 °C, and 180 °C, respectively.
CH:CHROMATOGRAPHY_TYPE           	GC
CH:INSTRUMENT_NAME               	Agilent GC7890B
CH:COLUMN_NAME                   	DB-5MS UI column (30 m, 0.25 mm i.d.)
CH:SOLVENT_A                     	not applicable
CH:SOLVENT_B                     	not applicable
CH:FLOW_GRADIENT                 	not applicable
CH:FLOW_RATE                     	1.0 ml/min
CH:COLUMN_TEMPERATURE            	not applicable
#ANALYSIS
AN:ANALYSIS_TYPE                 	MS
#MS
MS:INSTRUMENT_NAME               	Agilent 7250
MS:INSTRUMENT_TYPE               	QTOF
MS:MS_TYPE                       	EI
MS:ION_MODE                      	POSITIVE
MS:MS_COMMENTS                   	The mass spectrometer was operated in full scan mode, ranging from m/z 20-1200,
MS:MS_COMMENTS                   	with a data acquisition rate of 5 Hz. MS data was acquired using MassHunter
MS:MS_COMMENTS                   	software (version 10.0, Agilent Technologies, USA), utilizing three replicates
MS:MS_COMMENTS                   	to calculate the mean and the standard error.
#MS_METABOLITE_DATA
MS_METABOLITE_DATA:UNITS	micro molar
MS_METABOLITE_DATA_START
Samples	A01	A02	A13	A14	A20	A22	A23	A24	A25	A26	A27	A28	A29	A30	A31	A32	A33	A34	A35	A36	A37	A38	A39	A40	A41	A42	A43	A45	A46	B01	B02	B05	B06	B07	B08	B09	B10	B11	B12	B13	B14	B15	B16	B17	B18	B19	B21	B22	B23	B24	B25	B26	B27	B28	B30	B33	B34	B42	C01	C02	C03	C04	C05	C06	C07	C08	C09	C10	D01	D02	D03	D04	D05	D06	D08	D09	D10	D11
Factors	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	Sample source:Plasma | Disease:NSCLC | EGFR mutation:No | Treatment:Naïve	Sample source:Plasma | Disease:Healthy | EGFR mutation:n/a | Treatment:n/a	Sample source:Plasma | Disease:Healthy | EGFR mutation:n/a | Treatment:n/a	Sample source:Plasma | Disease:Healthy | EGFR mutation:n/a | Treatment:n/a	Sample source:Plasma | Disease:Healthy | EGFR mutation:n/a | Treatment:n/a	Sample source:Plasma | Disease:Healthy | EGFR mutation:n/a | Treatment:n/a	Sample source:Plasma | Disease:Healthy | EGFR mutation:n/a | Treatment:n/a	Sample source:Plasma | Disease:Healthy | EGFR mutation:n/a | Treatment:n/a	Sample source:Plasma | Disease:Healthy | EGFR mutation:n/a | Treatment:n/a	Sample source:Plasma | Disease:Healthy | EGFR mutation:n/a | Treatment:n/a	Sample source:Plasma | Disease:Healthy | EGFR mutation:n/a | Treatment:n/a	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:TKI resistant	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:TKI resistant	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:TKI resistant	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:TKI resistant	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:TKI resistant	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:TKI resistant	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:TKI resistant	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:TKI resistant	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:TKI resistant	Sample source:Plasma | Disease:NSCLC | EGFR mutation:Yes | Treatment:TKI resistant
Xylitol	2.445023129	2.372724058	2.941257662	3.552513444	42.78790476	8.416269131	4.732302831	2.477886343	4.029030049	3.315898303	2.638916092	2.767082627	3.641244122	3.115432697	5.179242542	20.37519274	3.026702019	22.36670352	5.366562863	9.481037268	2.960975591	18.34753243	3.536081837	5.277832185	3.207449696	2.553471736	10.08900673	5.241682649	2.852526984	4.058606941	8.353829025	3.953444656	5.813502575	3.358620481	2.369437737	3.756265372	1.942215953	0.801862424	2.257702809	3.506504945	3.325757267	7.795154385	11.31480462	3.989594192	2.836095377	2.23798488	4.186773476	12.64576479	1.396686599	3.49664598	2.809804806	1.574147955	2.326715558	2.763796306	6.119130466	2.941257662	8.567439916	2.385869344	2.487745307	3.887718228	3.440778516	4.666576402	4.715871224	3.950158335	4.77831133	8.22566249	3.8680003	9.20498627	11.64672308	2.960975591	5.212105756	22.26482755	13.046696	18.92921132	5.573601112	0.83801196	6.12898943	10.50965587
Adonitol	3.440778516	4.423388618	6.556211213	4.906477865	102.1355831	8.583871523	8.57729888	2.310283951	9.267426377	3.37833841	4.617281581	2.28399338	7.045873103	2.84266802	12.83637143	50.50747375	1.988224453	45.78502989	6.395181464	16.80953401	1.98165181	39.79077963	1.035191244	12.31384632	4.351089547	3.154868554	16.03396216	13.68424235	2.622484485	3.09900109	18.89634811	6.628510284	4.209777726	2.790086877	1.613583812	5.162810935	2.093386738	2.191976381	2.63234345	4.045461656	4.834178794	11.84061604	25.66617021	8.22566249	2.793373199	2.165685809	12.01479108	35.27537402	1.95864756	8.20265824	5.82664786	3.095714768	2.803232163	7.29563353	13.93400278	2.954402948	25.42298243	2.852526984	22.32726766	33.95098649	25.15021775	12.402577	9.573054268	19.91839407	15.81377863	8.754760237	18.42640415	14.52882695	7.13131746	3.7299748	8.662743237	27.97316784	18.649874	37.90443114	9.096537663	1.150212494	12.98096957	22.92866448
Fructose	9.466800699	4.726461914	12.02292015	25.46405641	61.22752572	17.268377	11.15977884	9.827599318	23.85711487	12.35318965	12.8610831	10.34381888	16.7882373	11.1209236	17.18789115	120.3624194	8.775732574	180.8211666	13.33844742	34.18983225	10.71849437	47.21466241	11.76203499	18.12596756	14.21269023	11.03488701	52.53227899	19.29995076	13.82691325	21.75893212	30.4597296	21.02068264	18.83923868	10.18284719	6.741383435	14.57348885	6.813543159	4.596019337	21.39535813	14.13220439	9.475126821	16.32197447	34.42573904	19.25554478	31.13692086	7.249276876	17.97054662	44.49202052	13.08588839	25.77212292	14.8454755	7.063326819	20.27410704	13.94070358	19.18893581	14.27652383	30.3209609	8.48154293	21.72285226	24.50100163	26.68522097	18.17037355	13.92960208	14.82327251	45.83530154	21.88104858	25.32251234	60.76403826	14.60956871	14.37088655	22.89406009	42.93503571	49.04918462	53.03462168	12.46697999	3.485869738	23.41305503	52.37685804
Glucose	301.5499354	148.8821626	142.6708756	175.1732805	86.68048063	495.6512665	359.3498742	302.1771699	322.9730472	536.9682592	137.4448464	704.0013677	298.5636329	634.5559596	329.7754889	1322.182621	577.0613119	LoQ	882.2636394	832.1681388	509.0701998	LoQ	850.3301862	143.3758206	504.9126895	686.91339	892.9571554	143.7449454	677.3633281	1112.086809	346.4443851	409.7090353	1035.791778	384.7195679	401.9407635	273.7240357	441.8978229	207.3259882	570.109	620.4848134	24.8562495	396.4927044	633.0683591	284.1094852	796.3547128	476.8481077	221.6080628	740.0340483	417.1609145	886.8152528	330.9439213	400.8306139	999.2900593	872.316699	509.2478237	862.2115623	531.4369388	676.6694846	1178.276704	1330.461561	1505.329551	874.1817504	442.5000791	366.9932542	LoQ	814.841479	464.6475636	592.9031467	332.1539844	569.6899186	139.5374784	169.5503728	961.7586768	183.2579449	115.4527828	199.2218961	384.2921603	LoQ
Mannitol	25.67082282	8.313580916	6.556997296	4.901966166	16.46797144	13.10576061	10.98139229	9.74354977	10.84141453	15.51831842	7.185524873	12.6309341	7.111419001	5.807704595	11.95849193	14.19264672	11.53306933	27.19411018	11.62089851	12.72699726	7.676819354	15.18895899	15.40029796	7.737201916	15.72416807	13.56137448	23.58487977	10.05918589	13.39943943	13.13046256	13.73977751	7.407842487	15.68848746	10.23484425	11.50836738	10.4763745	9.795698346	7.61369213	64.23332261	13.10576061	4.904710828	12.42508445	14.52749547	8.848789988	8.69234426	8.552366502	8.368474155	55.22808689	6.757357615	14.59885668	7.874435011	8.579813121	13.47628996	13.75624548	13.50099192	14.52475081	15.21366095	9.216574684	22.97556482	28.56369647	29.30201052	18.27395898	22.35801589	21.52363868	31.25895446	25.03131659	24.22438599	23.21983973	10.64105421	11.37113428	9.595338027	15.23561825	16.65460845	18.51823389	6.419764201	5.06664588	17.14041361	16.25663248
Inositol	0.349697123	0.321943383	0.513444189	1.823420715	1.803993097	1.024113004	0.521770311	0.2775374	0.613357653	1.115700346	0.324718757	0.802083085	0.93807641	0.388552359	0.710495743	1.848399081	0.893670427	6.247366864	1.254469046	0.804858459	1.121251094	1.978841659	0.430182969	0.596705409	1.20173694	0.294189644	1.107374224	0.674415881	1.196186192	1.443194478	0.96583015	0.518994937	1.457071348	0.815959955	0.441284465	1.384911624	0.255334408	0.652212889	0.316392635	0.852039817	0.652212889	0.635560645	2.328538782	0.316392635	0.679966629	0.410755351	0.713271117	1.226715306	0.219254546	1.24336755	0.507893441	0.20815305	0.432958343	1.268345916	0.879793557	0.469038205	1.379360876	0.996359264	24.98114133	20.51001383	34.30639796	26.32164697	15.69473994	21.41756112	22.3167823	25.20039588	28.08678483	32.89650797	0.605031531	1.323853396	0.971380898	0.691068125	1.371034754	2.36184327	0.946402532	0.546748677	0.771553971	2.517264214
Sucrose	5.106683825	4.91240781	2.668738944	6.26795775	15.78456105	4.731278292	5.344781498	7.141469457	5.645690213	4.598352598	3.201902444	6.555719968	4.515091448	5.245452407	5.214777247	9.799983348	4.780942838	12.81199194	5.447032032	6.089749676	7.109333575	7.72283678	4.122157253	4.672849416	5.755244357	6.104356895	9.145579929	4.816000164	5.676365373	12.25107473	4.925554307	4.38654792	8.644552311	5.352085108	7.706768839	5.950981094	4.364637091	4.154293135	7.426310231	10.18269249	4.240475728	8.014981164	9.215694581	5.331635001	12.72142718	4.139685916	7.963855897	20.99495613	26.00085014	19.10916413	3.749673163	3.938106291	7.017308094	7.667329348	7.870369694	9.96942709	10.69978805	32.16801808	13.76855023	14.2134921	13.06255038	8.187089727	8.988237057	12.68343798	15.44167481	8.997001172	13.38299507	20.17701619	5.896934383	12.84120638	8.591966322	11.06935069	11.3498093	12.13567769	6.828874967	3.036840867	5.815133956	11.27531248
Maltose	5.067244333	5.688051149	5.95536326	5.958284703	16.62447615	10.15055661	9.558964231	7.819244427	7.435074563	8.773095839	5.664679598	9.011193512	6.712017213	7.65418285	8.144985415	13.7687648	9.097376105	19.26546138	10.20168188	10.52157998	8.94838247	12.92154609	9.351541719	7.338666916	11.01676471	9.491771023	14.67441239	8.597809209	9.39828482	12.64546964	12.28613205	8.72781346	12.37669681	9.15434426	9.002429181	9.014114956	7.02169026	5.604789999	8.965911133	8.860739155	6.460773043	11.54846748	12.9288497	7.69216162	9.534131959	7.667329348	8.508705172	14.02146969	7.971159506	10.92473922	7.966777341	8.419601135	9.681664872	11.05328275	11.86106197	12.23500679	12.25691761	9.168951479	29.53579718	28.76745745	34.82361052	24.69058258	27.76248077	26.24332998	39.04947903	33.12625166	29.41747871	29.55770801	10.80496003	9.316484393	8.854896267	14.54440814	13.40796649	16.81437	7.294845258	5.321409947	9.586717948	10.29808952
MS_METABOLITE_DATA_END
#METABOLITES
METABOLITES_START
metabolite_name	Pubchem CID
Xylitol	6912
Adonitol	827
Fructose	5984
Glucose	5793
Mannitol	6251
Inositol	892
Sucrose	5988
Maltose	439186
METABOLITES_END
#END