Diagnostics of the future: mass spectrometry in detecting difficult-to-diagnose diseases

- We are developing a diagnostic test that is both sensitive and reliable, yet minimally invasive. It's a diagnostic panel that takes advantage of the benefits of mass spectrometry and can be carried out from a blood sample, even in young girls who have not yet had intercourse. Its proper design requires a properly planned study on a sufficiently large group of patients, says Professor Piotr Laudanski of the Department of Obstetrics, Women's Diseases and Gynecology Oncology, Faculty of Medicine, WUM.

Endometriosis is one of the diseases that can be effectively and accurately diagnosed in its early stages. According to WHO data, this affliction affects 190 million women and girls worldwide, and in Poland up to one in ten Polish women of reproductive age. In many cases it leads to infertility, but above all it is a source of pain that is difficult to control. Due to its location - deep in the abdominal cavity - and the dependence of symptoms on the hormonal cycle, it often takes many years until a diagnosis is made, during which women suffer and their bodies undergo - sometimes irreversible - changes.

- We have already collected results from plasma analyses of a group of patients, but we plan to confirm the effectiveness of our panels on a broader, independent group of women. In the near future, we plan to enroll patients in the study at more than a dozen centers in Poland. We are also open to talks with further investors to implement such panels into clinical practice in the near future," Prof. Laudanski adds.

- Our laboratory has the longest experience in the country in this type of research, the appropriate methodology and the most modern equipment. We are able to create diagnostic panels tailored to different needs. Panels can include dozens, and sometimes hundreds, of molecules. Unfortunately, without the involvement of doctors and the business community, the potential for their practical application remains untapped," explains Prof. Dr. Michal Dadlez, a biophysicist at the Institute of Biochemistry and Biophysics of the Polish Academy of Sciences, who manages the Mass Spectrometry Laboratory.

Mass spectrometry is a sensitive, accurate and relatively fast method

Mass spectrometry is an analytical technique that is used to qualitatively and quantitatively characterize the molecular composition of a test sample. It makes it possible to look for so-called markers, i.e. compounds or groups of compounds that indicate the existence of a particular disease or the possibility of its occurrence. Markers can also be useful in monitoring susceptibility to treatment.

Mass spectrometry can be extremely sensitive - depending on the characteristics of the sample being tested, it can detect even trace amounts of a given substance in the sample being tested. And its specificity - the ability to accurately identify specific chemical compounds, even in the presence of many other similar substances - is superior to other diagnostic methods.

Moreover, the spectrometer can determine up to dozens of markers in a single sample at a time. Therefore, this method works well for screening, where we want to quickly test the patient for a number of conditions.

Already today, thanks to mass spectrometry, dozens of inborn metabolic disorders, including phenylketonuria, can be studied from a dry drop of blood. Such research has been carried out at the Mother and Child Institute, among others, for many years. - Mass spectrometry, although it has been in use for a long time, is currently undergoing intensive development, and we see a wider field for its application. This approach has the potential to change diagnostics, offering patients faster and more precise diagnosis of many more diseases, explains Prof. Dadlez of the Institute of Biochemistry and Biophysics of the Polish Academy of Sciences, which is celebrating its 70th anniversary this year.

Mass spectrometry can also be used to create diagnostic panels that include multiple markers, which is particularly important for diseases for which a single characteristic parameter has so far not been identified. This potential of spectrometry is still untapped, and could improve the monitoring of many diseases.

Mass spectrometry can be used to study a wide variety of samples

- Currently, the best biological material for searching for markers and creating panels are blood plasma samples," says Emilia Samborowska, who works in Prof. Dadlez's team on metabolomics, i.e. analysis of low-molecular compounds of high biological significance in the body. - They provide the best reproducibility of results, mainly due to standardization of collection procedures and optimization of sample preparation for analysis. Moreover, the material is relatively easy to obtain, and the collection itself is minimally invasive, compared to at least a biopsy. Other samples can be much more affected by the collection conditions themselves, which disturbs the subsequent analysis result and its interpretation, he adds.

- However, should it turn out that other tissues are better suited for the diagnosis of a given disease, any biological material can be examined using mass spectrometry: urine, saliva, biopsy specimens, pleural or peritoneal effusions," adds Bianka Swiderska, who specializes in proteomics, or protein research.

Mass spectrometry speeds up diagnostics - in medicine and beyond

Endometriosis is just one of many examples of diseases in which the use of a diagnostic panel based on mass spectrometry can significantly accelerate the diagnosis. Therefore, there is talk of a new opening for this technique. Similar panels would be desirable for other diseases that cannot be diagnosed by traditional methods, where single markers are determined and the timing of treatment implementation is critical to the outcome. These include cancers such as lung cancer or pancreatic cancer, multiple sclerosis, Alzheimer's disease and many others.

- Mass spectrometry is also used in biopharmaceutical, environmental, toxicological and anti-doping tests, and even to check the conformity of goods with the manufacturer's declaration, explains Prof. Dadlez.

- This method stands out from others, such as those based on antibodies, because of its versatility and flexibility. We can study not only proteins, but also metabolites or lipids. In addition, for proteins we don't have to create antibodies, which is very complicated and expensive, and sometimes even impossible," Bianka Swiderska adds.

- When we are looking for new markers and don't know what to look for, mass spectrometry is practically irreplaceable. Mainly due to its ability to analyze many different compounds at the same time," adds Emilia Samborowska.

Diagnosis at hand, investors lacking

Even if a diagnostic panel is developed by scientists for a given disease, the dissemination of this method faces problems. Why?

- We have promising diagnostic solutions that can save lives, but in order to get them "into patients' beds" we now need centers interested in collaborating and creating modern diagnostic tools based on proteomic and metabolomic technologies and validating panels that have already been initially developed. These include panels for the diagnosis of endometriosis, analysis of pleural fluid in the diagnosis of lung cancer, or assessment of susceptibility to immunotherapy in breast cancer," explains Prof. Dadlez.

The development of a final diagnostic panel and its subsequent implementation in routine diagnostics requires the involvement of large financial resources and the work of many specialists from various fields, including biotechnology, biology, medicine, diagnostics or statistics. Professor Dadlez's team has specialized in research using mass spectrometry techniques for 23 years and has participated in thousands of studies. The latest project is precisely a diagnostic panel for endometriosis. The team is ready, in cooperation with business, to continue work in this area. However, this does not mean that IBB PAN will directly perform diagnostic tests on patients. Their role is to look for biomarkers, develop and optimize a diagnostic panel that can be implemented by medical centers in the future and ultimately go to patients.

Source: IBIN PAN