Final Report Summary - BREATH (Characterization of biomarkers in breath of lung and breast cancer patients)
Mass spectrometry, as stand-alone instrument or in combination with other separation techniques, has become an essential analytical tool in different fields. During this project we have used a rapid mass spectrometric approach termed Secondary Electrospray Ionization-Mass Spectrometry (SESI-MS), which enables the detection of volatile compounds in real time at concentrations below parts-per-trillion (ppt). In addition, we have explored the use of new statistical tools to assist in the data analysis.
Some of our accomplishments during the execution of this project can be summarised as follows:
- We have pursued a fundamental study on the still unclear ionisation mechanism of SESI. As a result, now that a better understanding of the mechanism is available, more rational choices for the conditions most suited for a given SESI analysis can be made.
- We used SESI-MS to monitor the breath metabolites of a group of healthy subjects during several months. Interestingly, we found that each subject had his/her own characteristic breath signature. This premise is important for metabolic studies given that one of the major issues is the different sources of temporal variability (e.g. diet, etc.) that ultimately changes the metabolic fingerprint within a subject. We found that, in spite of this 'temporal noise', there exist a stable metabolic fingerprint strongly individual-specific. This is consistent with previous metabolic studies.
- We have confirmed the notion that bacterial activity in mouth can pose a serious interference in the discrimination of systemic volatiles. In biomarker discovery, this may represent a curb, but on the other hand, this has shown potentiality as a sensitive and rapid tool to screen bacterial-related illnesses.
- Free fatty acids are important compounds involved in several metabolic routes, which have been quantified in breath.
- Once our technique was optimised, we investigated the differences in the breath patterns of a group of lung and breast cancer patients, and healthy controls with the aim of identifying a set of metabolites over or under expressed in cancer patients. This was motivated because several reports support the idea that dogs can identify cancer tissues based on their characteristic odour signature. The analysis of these data is currently under investigation.
- In addition, during this project we have extended the application of SESI-MS coupled to statistical analysis to the rapid analysis of virgin olive oils with the aim of tracing their geographical origin. This analytical strategy has shown a great potential to prevent economic fraud, such as false claims of geographical origin on product labels.
- Furthermore, we have validated our proposed statistical approach against traditional chemometric tools. During this exercise, we could successfully discriminate between a group of colo-rectal cancer patients and healthy controls based on their plasma mass spectral fingerprint.
- Moreover, we have explored the capabilities of a novel analytical instrument termed differential mobility analyser coupled to MS to probe a recently proposed prostate cancer biomarker. The main advantage of this technique is its analysis speed in comparison with traditional methods. This requirement is essential if the method were to be applied in large-scale clinical practice.
In summary, our work has advanced the development of rapid screening techniques aimed at diagnosing diseases in a non-invasive fashion. Benefits for the scientific community and the society as a whole are therefore clear. In addition, the possibility to trace with high precision the origin of virgin olive oils, may put at policy makers' disposal an appropriate instrument to support food quality and safety.
Some of our accomplishments during the execution of this project can be summarised as follows:
- We have pursued a fundamental study on the still unclear ionisation mechanism of SESI. As a result, now that a better understanding of the mechanism is available, more rational choices for the conditions most suited for a given SESI analysis can be made.
- We used SESI-MS to monitor the breath metabolites of a group of healthy subjects during several months. Interestingly, we found that each subject had his/her own characteristic breath signature. This premise is important for metabolic studies given that one of the major issues is the different sources of temporal variability (e.g. diet, etc.) that ultimately changes the metabolic fingerprint within a subject. We found that, in spite of this 'temporal noise', there exist a stable metabolic fingerprint strongly individual-specific. This is consistent with previous metabolic studies.
- We have confirmed the notion that bacterial activity in mouth can pose a serious interference in the discrimination of systemic volatiles. In biomarker discovery, this may represent a curb, but on the other hand, this has shown potentiality as a sensitive and rapid tool to screen bacterial-related illnesses.
- Free fatty acids are important compounds involved in several metabolic routes, which have been quantified in breath.
- Once our technique was optimised, we investigated the differences in the breath patterns of a group of lung and breast cancer patients, and healthy controls with the aim of identifying a set of metabolites over or under expressed in cancer patients. This was motivated because several reports support the idea that dogs can identify cancer tissues based on their characteristic odour signature. The analysis of these data is currently under investigation.
- In addition, during this project we have extended the application of SESI-MS coupled to statistical analysis to the rapid analysis of virgin olive oils with the aim of tracing their geographical origin. This analytical strategy has shown a great potential to prevent economic fraud, such as false claims of geographical origin on product labels.
- Furthermore, we have validated our proposed statistical approach against traditional chemometric tools. During this exercise, we could successfully discriminate between a group of colo-rectal cancer patients and healthy controls based on their plasma mass spectral fingerprint.
- Moreover, we have explored the capabilities of a novel analytical instrument termed differential mobility analyser coupled to MS to probe a recently proposed prostate cancer biomarker. The main advantage of this technique is its analysis speed in comparison with traditional methods. This requirement is essential if the method were to be applied in large-scale clinical practice.
In summary, our work has advanced the development of rapid screening techniques aimed at diagnosing diseases in a non-invasive fashion. Benefits for the scientific community and the society as a whole are therefore clear. In addition, the possibility to trace with high precision the origin of virgin olive oils, may put at policy makers' disposal an appropriate instrument to support food quality and safety.