EXPRESSION OF SPP1 AND SPARC GENES IN TUMOR TISSUE OF PATIENTS WITH BREAST CANCER.

BACKGROUND: Breast cancer (BCa) is one of the most common oncological diseases in women in Ukraine and worldwide, which determines the need to search for new diagnostic and prognostic markers. In this aspect, the study of multicellular proteins, in particular osteopontin (OPN) and osteonectin (ON), in BCа tissue is relevant. The aim of the work was to investigate the expression of SPP1 and SPARC at the mRNA and protein levels in BCa tissue and to assess their relationship with the main clinicopathological BCa characteristics and the survival rates of patients. MATERIALS AND METHODS: The work was based on the analysis of the results of the examination and treatment of 60 patients with stage II-III BCa and 15 patients with breast fibroadenomas. SPP1 and SPARC mRNA levels were determined by real-time PCR. The study of the expression of protein products of the SPP1 and SPARC genes was carried out by the immunohistochemical method. RESULTS: We have established that the BCa tissue was characterized by 3.5 (p < 0.05) and 7.4 (p < 0.05) lower levels of SPP1 and SPARC mRNA, respectively, compared to the tissue of benign neoplasms, while OPN and ON expression levels were 1.6 (p < 0.05) and 5.6 (p < 0.05) times higher, respectively, compared to fibroadenoma tissue. The analysis of the relationship between the expression of SPP1 and SPARC at the protein and mRNA levels in BCa tissue and the main clinicopathological BCa characteristics revealed its dependence on the presence of metastases in regional lymph nodes, differentiation grade, and the molecular BCa subtype. Also, high expression levels of SPP1 and OPN were associated with worse patient survival rates. CONCLUSION: The obtained results indicate the perspective of using SPP1 and SPARC expression indices in BCa tissue to assess the aggressiveness of the cancer course and optimize the tactics of treating patients.

TUMOR MICROENVIRONMENT-ASSOCIATED miR-7-5p, miR-19a-3p, AND miR-23b-3p EXPRESSION IN PROSTATE CANCER WITH DIFFERENT PROGRESSION RISK.

BACKGROUND: The tumor microenvironment (TME) plays an important role in the occurrence and progression of prostate cancer (PCa). At the same time, the mechanisms and features of the interaction between tumor cells and individual components of the TME in PCa remain not fully elucidated. The aim was to study the expression levels of tumor-associated miR-7-5p, miR-19a-3p, and miR-23b-3p in the PCa tissue and to analyze their relationship with the features of TME. MATERIALS AND METHODS: The work is based on the analysis of the results of the examination and treatment of 50 patients with PCa of stages II-IV. The expression of miRNA in the PCa tissue was analyzed by the real-time polymerase chain reaction. The expression of alpha-smooth muscle actin (α-SMA), vimentin (VIM), and CD68 in PCa tissue was determined by the immunohistochemical method. The identification of mast cells in the PCa tissue was assessed by the histochemical method. RESULTS: The analysis of the expression levels of tumor-associated miRNAs demonstrated that the tumor tissue of patients with a high risk of PCa progression was characterized by 4.93 (p < 0.01) and 8.97 (p < 0.05) times higher levels of miR-19a-3p and miR-23b-3p, respectively, compared to similar indicators in the group of patients with a low risk of PCa progression. The levels of miR-7-5p and miR-19a-3p expression in the PCa tissue correlated with the expression level of α-SMA (r = 0.49 and r = 0.45, respectively; p < 0.05) and VIM (r = 0.45 and r = 0.46; respectively, p < 0.05). A direct relationship (r = 0.44; p < 0.05) was established between the level of miR-7-5p expression and the degree of infiltration of the prostate gland tissue by tumor-associated macrophages. CONCLUSIONS: The features of the expression of tumor-associated miR-7-5p, miR-19a-3p, and miR-23b-3p indicated the prospect of their use as markers of the aggressiveness of the PCa course.

EXPRESSION PROFILE OF miR-145, -182, -21, -27a, -29b, and -34a IN BREAST CANCER PATIENTS OF YOUNG AGE.

BACKGROUND: Breast cancer (BC) in young women remains a significant public health concern. While progress has been made in understanding the etiology, diagnosis, and treatment of BC in this population, challenges persist. The identification and utilization of prognostic biomarkers offer valuable tools for tailoring treatment strategies and improving outcomes for BC patients. AIM: To evaluate the relationship between the expression of tumor-associated microRNAs and the clinical and pathological features of BC in young patients. MATERIALS AND METHODS: The work is based on the results of the examination and treatment of 50 women younger than 45 years with stage I-II BC. miR-145, -182, -21, -27a, -29b, and -34a expression in tumor samples was analyzed by the real-time reverse transcription polymerase chain reaction. RESULTS: Higher expression of miR-182, -21, and -29b and lower levels of miR-27a were associated with tumor stage in young BC patients. Patients without lymph node metastases (N0) had significantly higher levels of miR-182, -27a, and -34a and lower levels of miR-29b compared to N1 cases (p < 0.05). Expression of miR-145, -182, -21, -27a, and -29b was associated with molecular BC subtypes. CONCLUSION: Obtained results show that a high malignancy degree of BC in young women is associated with an increase in the miR-182, -21, -29b, and -34a expressions and a decrease in the miR-27a level in the tumor tissue, which indicates the prospects of the use of them for predicting the aggressiveness of the disease.

FEATURES OF BREAST CANCER IN PATIENTS OF YOUNG AGE: SEARCH FOR DIAGNOSIS OPTIMIZATION AND PERSONALIZED TREATMENT.

The statistical data of the recent decades demonstrate a rapid growth of breast cancer (BCa) incidence and a tendency toward its increase especially in young women. In the structure of morbidity of women in the age group of 18-29 years, BCa ranks first and in the age range of 15-39 years, BCa is one of the leading causes of mortality. According to the data of the epidemiological and clinical studies, the young age is an independent unfavorable prognostic factor of BCa that is associated with an unfavorable prognosis and low survival rates and is considered an important predictor of the disease aggressiveness, a high risk of metastasis and recurrence. The variability of clinicopathological and molecular-biological features of BCa in patients of different age groups as well as the varying course of the disease and different responses to the therapy are mediated by many factors. The analysis of the literature data on the factors and mechanisms of BCa initiation in patients of different age groups demonstrates that the pathogen- esis of BCa depends not only on the molecular-genetic alterations but also on the metabolic disorders caused by the current social and household rhythm of life and nutrition peculiarities. All these factors affect both the general con- dition of the body and the formation of an aggressive microenvironment of the tumor lesion. The identified features of transcriptome and the differential gene expression give evidence of different regulations of the immune response and the metabolic processes in BCa patients of different age groups. Association between the high expression of the components of the stromal microenvironment and the inflammatory immune infiltrate as well as the increased vascu- larization of the tumor lesion has been found in BCa tissue of young patients. Proving the nature of the formation of the landscape comprising molecular-genetic, cytokine, and immune factors of the tumor microenvironment will undoubtedly contribute to our understanding of the mechanisms of tumor growth allowing for the development of algorithms for delineating the groups at high risk of tumor progression, which requires more careful monitoring and personalized treatment approach. Th s will be helpful in the development of innovative technologies for complex BCa treatment.

PATTERN OF MMP2 AND MMP9 EXPRESSION DEPENDS ON BREAST CANCER PATIENTS' AGE.

BACKGROUND: Despite the large number of studies devoted to the study of the features of tumor microenvironment in breast cancer (BCa), presently there is no consensus on the features of MMP-2 and MMP-9 expression in the tumor tissue of BCa patients depending on the age. The aim of the study was to investigate the relationship between MMP-2 and -9 expression at the protein and mRNA levels in BCa tissues and the clinical and pathological features of BCapatientsin different age groups. MATERIALS AND METHODS: The expression level of MMP-2 and -9in the BCa tissue of patients of two age groups (< 45 years and > 45 years) was studied using the bioinformatics method (UALCAN database), immunohistochemical method, and real-time PCR. RESULTS: It was established that a characteristic feature of BCa in young patients is the low level of MMP2 mRNA against the background of increased expression of this gelatinase at the protein level, as well as decreased expression of MMP9 at both the mRNA and protein levels. When analyzing the correlation of the gelatinase expression indices in BCa tissue of young patients, depending on the clinical and pathological features, a significantly lower level of MMP-2 expression was recorded in BCa cases of stage II compared to the indices of stage I cases. High expression of MMP-2 and -9 was recorded in BCa tissue in node-positive cases and the basal molecular BCa subtype. CONCLUSIONS: The identified relationship between the expression of the studied gelatinases and such indices of BCa malignancy as its stage, positive regional lymph node status, and the molecular BCa subtype in young patients indicates the need for further research of the features of the tumor microenvironment to predict the cancer aggressiveness.

FEATURES OF COL1A1 EXPRESSION IN BREAST CANCER TISSUE OF YOUNG PATIENTS.

BACKGROUND: In the last decades, the incidence of breast cancer (BCa) in young women has been increasing steadily. The quantitative indicators of expression of collagen, which play important role in stromal microenvironment, and their association with the age and survival rates of BCa patients have not been yet definitively clarified. AIM: To investigate the relationship between the COL1A1 gene expression at the mRNA and protein levels in BCa tissue and the clinicopatological features and survival rates of BCa patients of different age groups. MATERIALS AND METHODS: The study was conducted on the clinical material of 50 patients with stage I-III BCa. COL1A1 gene expression at the mRNA and protein levels in BCa tissue were studied using the real-time PCR and immunohistochemical methods, as well as the bioinformatic analysis (UALCAN and Kaplan - Meier Plotter databases). RESULTS: The bioinformatic analysis showed that BCa tissue is characterized by 6.0 times (p < 0.05) higher level of COL1A1 mRNA compared to normal breast tissue. The correlation of COL1A1 expression at the mRNA and protein levels with the molecular subtype of neoplasms was demonstrated. According to Kaplan - Meier Plotter database, a low level of expression of COL1A1 protein level in BCa tissue is associated with lower rates of relapse-free survival of patients. The ex vivo study of the clinical material revealed a decrease in COL1A1 protein expression in tumor tissue of young patients with BCa of T3 category (p < 0.0374), low differentiation grade (p < 0.0163) and basal molecular subtype (p < 0.0001). A correlation between the expression of COL1A1 at the mRNA and protein levels and the expression status of estrogen receptors (p < 0.0001) and progesterone receptors (p < 0.0040) was established. The relapse-free 3-year survival rate of young BCa patients is significantly lower in the presence of a low COL1A1 optical density index in the tumor tissue. CONCLUSIONS: The identified relationship between COL1A1 expression and such indicators of BCa malignancy as tumor size, differentiation grade, molecular subtype, receptor status, and the recurrencefree survival of patients indicates the prospects of its use to predict the aggressiveness of the BCa course in young patients.