Summary of Study ST002082
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001322. The data can be accessed directly via it's Project DOI: 10.21228/M8TT44 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST002082 |
| Study Title | Predicting dying: a study of the metabolic changes and the dying process in patients with lung cancer |
| Study Type | Observational study |
| Study Summary | Background: Accurately recognising that a person may be dying is central for improving their experience of care. Yet recognising dying is difficult and predicting dying frequently inaccurate. Methods: Serial urine samples from patients (n=112) with lung cancer were analysed using high resolution untargeted mass spectrometry. ANOVA and volcano plot analysis demonstrated metabolites that changed in the last weeks of life. Further analysis identified potential biological pathways affected. Cox lasso logistic regression was engaged to develop a multivariable model predicting the probability of survival within the last 30 days of life. Results: In total 124 metabolites changed. ANOVA analysis identified 93 metabolites and volcano plot analysis 85 metabolites. 53 metabolites changed using both approaches. Pathways altered in the last weeks included those associated with decreased oral intake, muscle loss, decreased RNA and protein synthesis, mitochondrial dysfunction, disrupted β-oxidation and one carbon metabolism. Epinephrine and cortisol increased in the last 2 weeks and week respectively. A model predicting time to death using 7 metabolites had excellent accuracy (AUC= 0.86 at day 30, 0.88 at day 20 and 0.85 at day 10) and enabled classification of patients at low, medium and high risk of dying on a Kaplan-Meier survival curve. Conclusions: Metabolomic analysis identified metabolites and their associated pathways that change in the last weeks and days of life in patients with lung cancer. Prognostic tests based on the metabolites identified have the potential to change clinical practice and improve the care of dying patients. |
| Institute | University of Liverpool Institute of Life Course & Medical Sciences |
| Last Name | Norman |
| First Name | Brendan |
| Address | William Henry Duncan Building, 6 West Derby Street, Liverpool, UK. L7 8TX |
| bnorman@liverpool.ac.uk | |
| Phone | (+44)151 794 9064 |
| Submit Date | 2022-01-24 |
| Num Groups | 6 |
| Total Subjects | 112 |
| Num Males | 67 |
| Num Females | 45 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | d |
| Analysis Type Detail | LC-MS |
| Release Date | 2022-02-24 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
| Analysis ID | AN003396 | AN003397 | AN003398 | AN003399 |
|---|---|---|---|---|
| Analysis type | MS | MS | MS | MS |
| Chromatography type | Reversed phase | Reversed phase | HILIC | HILIC |
| Chromatography system | Agilent 6550 | Agilent 6550 | Agilent 6550 | Agilent 6550 |
| Column | Waters Atlantis dC18 (100 x 3mm,3um) | Waters Atlantis dC18 (100 x 3mm,3um) | Waters BEH Amide (150 x 3.0mm,1.7um) | Waters BEH Amide (150 x 3.0mm,1.7um) |
| MS Type | ESI | ESI | ESI | ESI |
| MS instrument type | QTOF | QTOF | QTOF | QTOF |
| MS instrument name | Agilent 6550 QTOF | Agilent 6550 QTOF | Agilent 6550 QTOF | Agilent 6550 QTOF |
| Ion Mode | NEGATIVE | POSITIVE | NEGATIVE | POSITIVE |
| Units | Values are raw peak area | raw peak area | raw peak area | Values are raw peak area |
Chromatography:
| Chromatography ID: | CH002511 |
| Chromatography Summary: | LC method 1: employed an Atlantis dC18 column (3x100 mm, 3 µm, Waters, UK) maintained at 60 °C with flow rate at 0.4 mL/min. Mobile phases were (A) water and (B) methanol both containing 5 mmol/L ammonium formate and 0.1 % formic acid. The elution gradient started at 5 % B at 0 to 1 min increasing linearly to 100 % by 12 min, held at 100 % B until 14 min, returning to 95 % A for 5 min. |
| Instrument Name: | Agilent 6550 |
| Column Name: | Waters Atlantis dC18 (100 x 3mm,3um) |
| Column Temperature: | 60 |
| Flow Gradient: | The elution gradient started at 5 % B at 0 to 1 min increasing linearly to 100 % by 12 min, held at 100 % B until 14 min, returning to 95 % A for 5 min |
| Flow Rate: | 0.4 mL/min |
| Solvent A: | 100% water; 0.1 % formic acid; 5 mM ammonium formate |
| Solvent B: | 100% methanol; 0.1 % formic acid; 5 mM ammonium formate |
| Chromatography Type: | Reversed phase |
| Chromatography ID: | CH002512 |
| Chromatography Summary: | LC method 2: used a BEH amide column (3x150 mm, 1.7 µm, Waters, UK) maintained at 40 °C with flow rate at 0.6 mL/min. Mobile phases were (A) water and (B) acetonitrile both containing 0.1 % formic acid. The elution gradient started at 99 % B, decreasing linearly to 30 % from 1 to 12 min, held at 30 % B until 12.6 min, returning to 99 % B for 3.4 min. Sample injection volume was 1 µL for both LC methods. |
| Instrument Name: | Agilent 6550 |
| Column Name: | Waters BEH Amide (150 x 3.0mm,1.7um) |
| Column Temperature: | 40 |
| Flow Gradient: | The elution gradient started at 99% B, decreasing linearly to 30% from 1 to 12 min, held at 30% B until 12.6 min, returning to 99% B for 3.4 min. |
| Flow Rate: | 0.6 mL/min |
| Solvent A: | 100% water; 0.1% formic acid |
| Solvent B: | 100% acetonitrile; 0.1% formic acid |
| Chromatography Type: | HILIC |
