Proteomics: from protein profiles to clinical solutions

Proteomics is the science that studies the proteome, that is, the set of all proteins synthesized by a cell, organ, or organism at a particular point in time. It is a dynamic information system that changes under the influence of environmental conditions, diseases, medications, or stress. It is these changes that provide the key to understanding the mechanisms of diseases, their early diagnosis, and the choice of therapy.

From genes to proteins: why the proteome is more important in the clinic

While the genome is a permanent structure that reflects hereditary information, the proteome reflects real cell activity. It determines which proteins are produced, in what quantities, what their activity is, and how they interact.

Professor Lyudmila Andrusenko, a molecular biologist, notes:
«"The genome says what could be. The proteome shows what actually is"».

Proteomics in medicine: four key directions

1. Biomarkers for early diagnosis
Proteins that change their concentration in the early stages of the disease are used as markers. For example, an increase in troponin levels is one of the main diagnostic criteria for myocardial infarction.

2. Assessment of treatment dynamics
Proteomics allows us to identify how the protein profile changes under the influence of drugs. This is important when monitoring chemotherapy, antibiotic therapy, and hormonal treatment.

3. Personalization of therapy
The individual characteristics of the patient's protein profile are taken into account when choosing drugs, dosage, and duration of the course. This is the basis of precision pharmacology.

4. Development of new drugs
Proteomics makes it possible to identify target proteins — key links in pathogenesis that can be inhibited or activated using pharmacological agents.

How proteomic analysis works

The process consists of the following stages:

• sample preparation (plasma, serum, tissues, cell lines);

• protein extraction;

• separation of protein fractions;

• identification using mass spectrometry or protein chips;

• quantitative analysis;

• bioinformatic comparison with databases of normal and pathological proteomes.

Depending on the study, the following technologies are used:

• LC-MS/MS (liquid chromatography with mass spectrometry);

• MALDI-TOF;

• iTRAQ (isobaric labeling);

• SWATH-MS (wideband scanning);

• SILAC (labeled cell cultivation);

• Western blot for validation of individual proteins.

Example: proteomics in oncology

Mass spectrometry was used in a patient with suspected ovarian cancer. The protein profile revealed increased expression of the HE4 protein. This allowed us to clarify the diagnosis and prescribe targeted therapy taking into account the sensitivity of the tumor tissue.

Result: chemotherapy was more effective, with fewer side effects than with standard treatment.

Proteomics and chronic diseases

Studies of type 2 diabetes have shown that even before clinical signs appear, patients' blood levels of certain proteins, including apolipoproteins and iron transport proteins, change. This opens up the possibility preclinical screening, when the glucose level does not yet exceed the norm.

Clinical implementation: benefits and barriers

Advantages:

• accuracy and sensitivity of methods;

• objectivity of results;

• high informativeness in complex cases;

• the possibility of studying individual reactions.

Barriers:

• high cost of equipment and tests;

• the difficulty of interpreting results without a multidisciplinary approach;

• the need for standardization of protocols;

• lack of widespread awareness among practicing physicians.

Proteomics beyond medicine

Proteomics is actively used in veterinary medicine, pharmaceuticals, the food industry (protein quality control), agrobiotechnologies (determination of stress resistance in plants), forensics, and ecology (monitoring of pollution biomarkers).