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S. Scott Helms
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P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.04-077 - Diagnosis and Prognosis of Non-Small Cell Lung Cancer Based on Metabolic Profiles of Mediastinal Lymph Node Aspirates (ID 3050)
09:30 - 09:30 | Author(s): S. Scott Helms
- Abstract
Background:
Non-small cell lung cancer (NSCLC) has a high mortality. TNM staging has prognostic implications, but there is a paucity of biomarkers to predict prognosis. The aim of this study was to evaluate the metabolomic profiles of mediastinal and hilar lymph nodes of NSCLC patients and to determine the prognostic implications of different metabolites.
Methods:
Endobronchial ultrasound-guided fine needle aspirates of hilar and mediastinal nodes from patients with NSCLC were collected from January 2011 to February 2013. Metabolomic profiles were generated using liquid chromatography mass spectrometry. Electronic medical records were reviewed for histologic diagnoses and survival status. T-testing was used to compare metabolite differences between groups. Metabolites dichotomized at their median values were assessed for prognostic potential via Cox regressions. P<0.05 was regarded as statistically significant.
Results:
A total of 79 lymph node aspirates were collected. 50 were positive for NSCLC, 13 were negative for NSCLC in patients with biopsy-proven NSCLC at the primary site, and 16 were from patients with non-malignant lung disease. The histologic subtypes of patients with NSCLC were 38 (60.3%) adenocarcinoma (AD) and 25 (39.7%) squamous cell carcinoma (SCC). TNM staging for the patients with NSCLC was as follows: 8 (12.7%) stage I, 10 (15.9%) stage II, 23 (36.5%) III, and 22 (34.9%) IV. Concentrations of alanine, alpha-ketoglutarate, glutathione (reduced and oxidized states), homocysteine, malate, melatonin, malonyl-carnitine, S-adenosyl homocysteine, and S-adenosylmethionine were statistically significantly higher in NSCLC patients than in patients with benign disease. In contrast, citruline, cysteine, glutamine, isoleucine, L-carnitine, leucine, ornithine, tryptophan, and valine were lower in the NSCLC group than in the benign group. Metabolite concentrations were different for different cancer sub-types; SCC patients had a 4.92-fold higher concentration of succinate than AD (p<0.0001), whereas AD had a 1.52-fold higher concentration of homocysteine than SCC (p=0.041). Elevated concentrations of the following metabolites were associated with shorter overall survival: melatonin (HR=2.24, 95% CI: 1.27-3.97; p=0.0057) Figure 1, malate (HR=1.91, 95% CI: 1.08-3.35; p=0.025), cystathionine (HR=1.84, 95% CI: 1.03-3.28; p=0.039), and glutamate (HR=1.77, 95% CI: 1.01-3.09; p=0.045). Figure 1
Conclusion:
Metabolomic data demonstrate differences between different NSCLC subtypes. In addition, metabolomic data may have prognostic potential that is independent from that associated with TNM stage. Metabolites associated with worsened prognosis offer an avenue for research; they may allow us to identify specific pathways that correlate with prognosis.
