They are looking for cancer markers in saliva

OmSPU conducts research on biochemical markers of oncological diseases in saliva

Lyudmila Belskaya, OmSPU

Currently, Omsk State Pedagogical University is conducting research on the topic: "A comprehensive study of biochemical markers of cancer in saliva to develop a personalized approach to the management of cancer patients."

The most promising biological fluid for the development of methods for the diagnosis of oncological diseases is human saliva. The advantages of saliva in comparison with venous or capillary blood are due to the non-invasiveness of collection and the absence of the risk of infection when receiving biomaterial. At the same time, saliva adequately reflects the biochemical status and physiological state of a person. This biomaterial is widely used not only in clinical practice, but also in hygienic and toxicological studies, as well as for studying the pharmacodynamics of medicines and for special scientific purposes.

Currently, considerable attention is paid to the characterization of the composition of saliva for a wide range of diagnostic tasks. However, in relation to oncological diseases, there is no universal indicator or a combination of complementary indicators that can be used for diagnosis, due to the significant heterogeneity of the disease. As part of the research, possible criteria for distinguishing samples from healthy and sick subjects were described in detail, correlations with oncogenesis parameters were revealed. At the same time, potential biomarkers are investigated both individually, including previously undescribed in relation to the diagnosis of cancer, and previously unexplored combinations of known biochemical markers. The proposed approach is fundamentally new, since, despite numerous studies devoted to the study of individual components of saliva, their comprehensive assessment using multidimensional statistical methods has not been carried out, nor have correlations with the molecular characteristics of tumors been investigated.

To date, saliva has been studied in 6,200 patients in parallel with a standard clinical and laboratory diagnostic procedure and the potential applicability of saliva for non-invasive diagnosis of oncological diseases has been evaluated, taking into account the heterogeneity of this group of diseases. The study group includes patients with the following groups of diseases:

• lung (lung cancer – 606, non–malignant pathologies - 176)
  breast cancer (breast cancer – 916, non–malignant pathologies - 755)
  uterine body (cancer – 262, non–malignant pathologies – 98), cervix (cancer – 74, non–malignant pathologies – 11), ovaries (cancer - 236, non-malignant pathologies - 131)
  prostate gland (cancer – 265, non–malignant pathologies - 190)
  stomach (cancer – 262, non–malignant pathologies – 16), esophagus (cancer – 26, non–malignant pathologies – 4), intestines (cancer – 511, non–malignant pathologies - 48), liver and pancreas (cancer - 121, non-malignant pathologies - 23)
  kidney (cancer – 228, non–malignant pathologies – 11), bladder (cancer – 126, non-malignant pathologies - 11)
  thyroid gland (cancer – 271, non–malignant pathologies - 96)
  tumors of the head and neck (cancer – 73, non–malignant pathologies - 53)
  skin and soft tissues (cancer – 390, non–malignant pathologies - 153)
  lymphomas (179)

The control group includes 1000 conditionally healthy patients.

For each patient included in the study, the following studies were carried out: determination of tumor size, lesions of peripheral lymph nodes, TNM staging, histological type, growth form, degree of malignancy, determination of biological markers of the tumor. Before the start of treatment, saliva samples were obtained, in which the biochemical composition (mineral composition, activity of metabolic enzymes, protein composition, activity of antioxidant enzymes, the level of lipid peroxidation products, medium-molecular peptides, etc.), pro-inflammatory and anti-inflammatory cytokines were determined. Additionally, the biochemiluminescent properties of saliva were determined, and saliva was studied by IR-Fourier spectroscopy. For each patient, statistical data on the treatment was collected, the effectiveness of therapy was evaluated, and the indicators of overall and relapse-free survival will be evaluated at the next stage. The biochemical markers of saliva were evaluated during treatment and during the control of relapse.

To date, the bulk of biochemical studies in 7,200 patients included in the study have been completed. The methods of chemical analysis were selected and adapted, diagnostic parameters were identified, and an algorithm for conducting a study of human saliva was compiled. The choice of the analysis conditions providing the greatest sensitivity and reproducibility of the results is justified. Factors (age, daily fluctuations) that potentially affect the result of determining the biochemical parameters of saliva have been studied. Methodological recommendations on the conditions of saliva collection have been prepared, as well as the necessary information for questioning patients has been clarified. For all samples, the biochemical composition of saliva was determined by 35 indicators, 10 potentially informative indicators were identified, the values of which are embedded in the diagnostic algorithm. An algorithm for data processing using various methods has been developed (linear discriminant analysis, naive Bayesian classifier, SVM support vector machine, GBM gradient boosting, Random Forest Random Forest, kNN k-nearest neighbor method). The diagnostic characteristics of the developed test were determined by the method of cross-validation, as well as by the method of double-blind testing. The values of sensitivity (70-75%) and specificity (85-90%) were preliminarily estimated by cross-validation.

According to the results of the work, more than 50 papers have been published, including RSCI – 20, WoS – 8, Scopus – 21 articles, 20 abstracts of conferences of various levels. Within two years, 1 doctoral and 1 candidate dissertation are planned to be defended.

About the author:
Lyudmila Vladimirovna Belskaya – Candidate of Chemical Sciences, Head of the Laboratory of the Department of Biology and Biological Education.

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