Research and Applications of Non-target and Targeted Metabolomics in Urine Samples

Author: Prime Jones

Lung cancer mortality ranks first among all malignancies worldwide, and the survival rate is quite low. Currently, there are two methods for diagnosis, low-dose spiral CT (LDCT) (high false positive rate and radiation damage) and tumor tissue testing (gene mutation screening). There is no non-invasive clinical diagnosis mark to guide the treatment for now. The research paper (Non-invasive urinary metabolomic profiling identifies diagnostic and prognostic markers in lung cancer, Cancer Research IF=9.3215) introduced today aims to find biomarkers for lung cancer diagnosis by performing metabolomics tests on urine.

There are three main reasons why this paper can get a good score, great samples, techniques and data analysis.

Samples Used in the Experiment

Prescreening samples (1005 cases): samples collected in 10 years(1998~2007) from 469 patients (urine collected before the treatment) and 536 healthy people.

Samples for later validation (158 cases): Samples collected in 2008-2010 from 80 patients (urine collected before the treatment) and 78 healthy people.

Tissue samples: 48 tumor tissue samples and its surrounding non-tumor tissue samples

Technical Workflow: initial non-targeted screening and post targeted MRM validation

Research results

Initial screening

Untargeted metabolomics analysis of pre-screened samples detected 1807 new numbers in positive ion mode and 1359 in negative ions. Through the detection of smoking-related metabolites (cotinine, nicotine-N'-oxide and trans-3'-hydroxycotinine), it was found that the smoking population was well separated from the non-smokers, and the feasibility of the analytical method was verified.

Data Analysis

Diagnostic and typing study: After applying statistical analysis to exclude human and gender interference, the authors identified four differential metabolites: NANA, cortisol sulfate, creatine riboside and 561+ (unidentified material). ROC analysis found that four differential metabolites had an AUC value between 0.63 and 0.76 in all populations and between 0.59 and 0.70 in stage I-II lung cancer patients. Among them, creatine riboside or all four metabolites were predicted to be more accurate (P