Features of the expression of the transcription factor NF-kB in patients with secondary edematous breast cancer with various pro-inflammatory cytokines

Abstract

Background. One of the most prominent features of secondary edematous breast cancer (SEBC), which is the most malignant form of this type of cancer, is severity of chronic inflammation that is important for pathogenesis and progression of the disease. As of now, there is evidence of association of carcinogenesis and inflammation. The transcription factor (NF-kB) and pro-inflammatory cytokines play a pivotal role in both inflammation and carcinogenesis. The regulation of NF-kB signal pathways is impaired in a lot of malignant diseases, including breast cancer (BC). Thus, the study of the content of pro-inflammatory cytokines and NF-kB is of high priority, as it can provide valuable information about the course of the tumor process. However, there are few research papers that deal with association of cytokine profile and NF-kB in breast tumors. Purpose – is to study the content of NF-kB-р105 and pro-inflammatory cytokines (IL-6, IL-8, TNFα) in the blood serum of patients with secondary edematous breast cancer. Materials and Methods. 87 patients (42 with SEBC, 45 with BC) were examined prior to treatment. The age of 42 patients with T4bN0-3M0 SEBC ranged from 34 to 71 years (median 53.1). The ductal cancer was found in 30 patients (71.43%), the lobular cancer – in 12 patients (28.57%). The tumor of more than 5 cm was detected in 20 individuals (47.6%), the tumor of less than 5 cm – in 22 individuals (52.4%). The comparison group consisted of 45 patients with BC, with their age ranging from 30 to 67 years (median 52.3). They had T3-4N1-3M0 non-edematous locally advanced BC. The tumor of more than 5 cm was detected in 12 patients (26.7%), the tumor of less than 5 cm – in 33 patients (73.3%). The ductal cancer was diagnosed in 33 patients (73.3%), the lobular cancer – in 12 patients (26.7%). The control group consisted of 10 patients with fibroadenomas. The content of cytokines (IL-1B, IL-2, IL-6, IL-8, TNFα) in the blood serum of patients was measured using the ELISA assay and CJSC «Vektor-Best» standard assay kits. The content of NF-kB1 subunit (р105 → р50) was measured using the ELISA assay and the Human NFkB – p105 (Nuclear factor NF-kappa-B p 105 subunit) ELISA Kit. The measurement was performed using the Immunochem-2100 American semi-automatic immunoassay analyzer. Results. It was found that in SEBC, the levels of pro-inflammatory cytokines IL-6, IL-8, TNFα were increased by 1.4 times, compared to the parameters in BC, and the level of IL-8 was the highest. The total level of NF-kB increased by 14,7 times in patients with SEBC and by 2,4 times in patients with BC, compared to individuals with fibroadenomas. The level of NF-kB in SEBC in groups with IL-6, TNFα was higher than in groups with BC by 3.1 and 1,7 times, respectively. It was found that the highest level of NF-kB was in the group with cytokine IL-8. In SEBC, it was higher by 5.7 times than in BC. In patients with SEBC, correlations between NF-kB and cytokines were established: NF-kB and IL-8 (r = 0.80; p < 0.05); NF-kB and IL-6 (r = 0.60; p < 0.05); NF-kB and TNFα (r = 0.60; p < 0.05). Thus, one feature of SEBC is the increase in the content of NF-kB, IL-6, and TNFα, and also a significant increase in the level of NF-kB and IL-8, compared to the parameters in patients with BC as well as in patients with fibroadenomas. Conclusions. It was found that there was activation of the transcription factor NF-kB-p105 and a significant increase in the levels of pro-inflammatory cytokines (IL-6, IL-8, TNFα) in the blood serum of patients with SEBC, compared to patients with fibroadenomas, which indicates high carcinogenic potential of the tumor and the presence of the inflammatory component. It was demonstrated that the highest level of NF-kB-p105 was detected in the group of patients with SEBC with the highest level of cytokines IL-8. It was also found that in patients with SEBC, the level of the transcription factor and pro-inflammatory cytokines IL-6, IL-8, TNFα in the blood serum was significantly higher than in patients with BC, thereby confirming severe aggressiveness of this form of the disease.