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nitchawat Paiyabhroma



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    P2.11 - Screening and Early Detection (ID 178)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Screening and Early Detection
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.11-25 - Pre- and Post-Surgery Metabolomic Profiles in Early-Stage NSCLC Patients (ID 2476)

      10:15 - 18:15  |  Author(s): nitchawat Paiyabhroma

      • Abstract
      • Slides

      Background

      Finding biomarkers to detect cancer at its early stage is of importance. Since metabolic reprogramming is a hallmark of cancer, oncometabolite is thus a promising target.Progress in cancer metabolomics opens the door for large scale screening of cancer-specific metabolites that could be future applied for subclinical stage detection and novel therapeutic targets.

      Method

      Seventy paired pre- and postoperative plasma samples of early-stage NSCLC patients who had completed curative surgery during 2015-2018 with ≥ 3 months disease free were retrieved. Demographic and Clinical data were collected. All samples were subjected to targeted metabolomics analysis using AbsoluteIDQ® p180 Kit on ESI 5500 LC-MS/MS System equipped with 1260 Series HPLC, according to the manufacturer's instruction.Multivariate analysis including PCA and OPLS-DA were used to identify the difference between pre- vs post-operative sample set. T-test was used to confirmed if the metabolites significantly different among groups at the univariate level (p < 0.05).

      Result

      Of the 70 patients, 31 (44.3%) were male and 39 (55.7%) were female. Median age was 63 years old (23 - 85). Majority of them were never-smokers (64.3%). Adenocarcinoma was the most common histology (91.4%). EGFR mutation was tested in 34 (48.6%) patients, of which, 22(64.7%) of them were positive. Metabolomic analysis revealed tryptophan as the most statistically significant change, together with other amino acids, carnitines, biogenic amines, and lipids (Table1). Besides glutamate, all metabolites increased postoperatively.Metabolites with VIP scores (Variable Importance in Projection) ≥ 1.5, including tryptophan, lysophosphatidylcholine-acyl C16:0, lysophosphatidylcholine-acyl C18:0, and carnitine, were assembled together for a predictive model which will be presented at the congress.

      Table 1: Metabolites with significant difference between pre- and post-surgery in early-stage NSCLC patients

      Metabolite (ng/ml)

      Pre operation (N=70)

      Post operative (N=70)

      Fold change

      p-value

      VIP score

      Mean

      SD

      Mean

      SD

      Amino acid

      Glutamate

      17,449.31

      7,808.80

      10,192.53

      5,294.28

      -0.374

      <0.001

      1.21

      Glutamine

      87,406.56

      22,839.10

      104,994.00

      26,276.52

      0.324

      <0.001

      0.77

      Arginine

      10,869.44

      5,082.21

      16,101.94

      8,220.61

      0.481

      <0.001

      0.79

      Asparagine

      5,023.79

      1,294.80

      7,630.93

      2,343.85

      0.663

      <0.001

      1.34

      Tryptophan

      6,921.41

      1,579.37

      13,189.77

      4,105.45

      0.992

      <0.001

      1.70

      Acrylcarnitine

      carnitine (C0)

      4,680.23

      1,292.54

      7,263.51

      2,136.29

      0.657

      <0.001

      1.50

      Biogenic amine

      Creatinine

      7,262.43

      2,410.21

      10,529.83

      4,070.33

      0.536

      <0.001

      1.14

      Kynurenine

      363.42

      126.06

      571.91

      232.05

      0.723

      <0.001

      0.82

      Sphingolipid

      SM C16:1

      8,837.49

      2,290.28

      10,875.53

      2,970.15

      0.290

      <0.001

      1.33

      SM C20:2

      178.18

      60.77

      205.47

      66.55

      0.304

      0.005

      0.43

      Phosphatidylcholine

      lysoPC a C16:0

      26,863.83

      6,420.81

      45,877.36

      13,732.55

      0.774

      <0.001

      1.67

      lysoPC a C16:1

      740.24

      287.44

      1,256.99

      588.67

      0.842

      <0.001

      1.33

      lysoPC a C17:0

      303.24

      90.78

      521.36

      200.39

      0.853

      <0.001

      1.45

      lysoPC a C18:0

      8,449.64

      2,593.82

      14,854.50

      5,047.03

      0.885

      <0.001

      1.60

      lysoPC a C18:2

      6,818.04

      2,466.61

      11,990.73

      4,760.87

      0.965

      <0.001

      1.37

      Conclusion

      We identified a distinct cluster of significant metabolic biomarkers associated with early-stage NSCLC. Tryptophan is the most significant one that associated with cancer metabolome. These would be potential biomarker profile for early-stage NSCLC detection.Larger cohort is needed to be validated.

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