ABSTRACT
Breast cancer patients with lymphatic metastasis suffer from poor prognoses. There is an urgent need for controlling lymph node metastasis, but it has proven challenging so far. Here, we implemented LASSO analysis of The Cancer Genome Atlas database to identify genes related to lymph node metastasis and prognosis, and 15 genes were selected. We constructed a functional protein association network and univariate Cox regression to identify significant genes. The results showed that BAHD1 could be predictive of lymph node metastasis as well as prognosis. In vitro studies demonstrated that BAHD1 exerted appreciable effects on the proliferation, migration, and invasion capacity of breast cancer cells. Furthermore, downregulation of BAHD1 induced cell cycle arrest in G1 phase. Additionally, the mRNA levels of CCND1, CDK1 and YWHAZ were decreased upon BAHD1 silencing. These findings indicate that the expression of BAHD1 is essential in the progression of breast cancer, which may provide novel therapeutic and diagnostic clues and insights into the prevention of lymph node metastasis in breast cancer.
Subject(s)
Breast Neoplasms , Breast Neoplasms/pathology , Cell Proliferation/genetics , Chromosomal Proteins, Non-Histone , Female , Humans , Lymphatic Metastasis , Prognosis , RNA, Messenger/genetics , RNA, Messenger/metabolismABSTRACT
BACKGROUND: In the early stage of severe burn, patients often exhibit a high level of inflammatory mediators in blood and are likely to develop sepsis. High-volume haemofiltration (HVHF) can eliminate these inflammatory mediators. We hypothesised that early application of HVHF may be beneficial in reducing sepsis and improving the prognosis of patients with severe burns. METHODS: Adults patients with burns ≥ 50% total burn surface area (TBSA) and in whom the sum of deep partial and full-thickness burn areas was ≥ 30% were enrolled in this randomised prospective study, and they were divided into control (41 cases) and HVHF (41 cases) groups. Patients in the control group received standard management for major burns, whereas the HVHF group additionally received HVHF treatment (65 ml/kg/h for 3 consecutive days) within 3 days after burn. The incidence of sepsis and mortality, some laboratory data, levels of inflammatory cytokines in the blood, HLA-DR expression on CD14+ peripheral blood monocytes, the proportion of CD25+Foxp3+ in CD4+ T lymphocytes, and the counts of CD3+, CD4+ and CD8+ T lymphocytes were recorded within 28 days post-burn. RESULTS: The incidence of sepsis, septic shock and duration of vasopressor treatment were decreased significantly in the HVHF group. In addition, in the subgroup of patients with burns ≥ 80% TBSA, the 90-day mortality showed significant decreases in the HVHF group. The ratio of arterial oxygen partial pressure to the fraction of inspiration oxygen was improved after HVHF treatment. In the patients who received HVHF treatment, the blood levels of inflammatory cytokines, including tumour necrosis factor-α, interleukin (IL)-1ß, IL-6 and IL-8, as well as the blood level of procalcitonin were found to be lower than in the control group. Moreover, higher HLA-DR expression on CD14+ monocytes and a lower proportion of CD25+Foxp3+ in CD4+ T lymphocytes were observed in the patients in the HVHF group. CONCLUSIONS: Early application of HVHF benefits patients with severe burns, especially for those with a greater burn area (≥ 80% TBSA), decreasing the incidence of sepsis and mortality. This effect may be attributed to its early clearance of inflammatory mediators and the recovery of the patient's immune status. TRIAL REGISTRATION: Chinese Clinical Trial Register, ChiCTR-TRC-12002616 . Registered on 24 October 2012.