The ratio of lymphocyte/red blood cells and platelets/lymphocytes are predictive biomarkers for lymph node metastasis in patients with breast cancer.

BACKGROUND: Axillary lymph node metastasis (LNM) affects the progression of breast cancer. However, it is difficult to preoperatively diagnose axillary lymph node status with high sensitivity. Therefore, we hypothesized that platelets/lymphocytes ratio (PLR) and lymphocytes/ red blood cells ratio (LRR) might help in the prognosis of lymph node metastasis in T1-T2 breast cancer. METHODS: 166 patients (Chang Ning Maternity & Infant Health Institute) were included in our study, and the associations of PLR and LPR with lymph node metastasis were investigated. Peripheral blood was collected one week before the surgery, and the patients were divided into different categories based on their PLR and LRR. RESULTS: The incidence of LNM was significantly increased in the high PLR group (p= 0.002) compared with the low PLR group; LNM was also significantly increased in the low LRR group (p= 0.036) compared with the high LPR group. Further, our study revealed that high PLR (p< 0.001, OR = 4.397, 95% CI = 2.005-9.645), low LRR (p= 0.017, OR = 0.336, 95%CI = 0.136-0.825) and high clinical T stage (p< 0.001, OR = 3.929, 95%CI = 1.913-8.071) are independent predictors of LNM. CONCLUSIONS: PLR and LRR could be identified as predictors of LNM in patients with T1/T2 breast cancer.

Hsa_circ_0007823 Overexpression Suppresses the Progression of Triple-Negative Breast Cancer via Regulating miR-182-5p-FOXO1 Axis.

Background: This study aimed to analyze the specific expression of hsa_circ_0007823 in triple-negative breast cancer (TNBC) and explore the roles and related molecular mechanisms of hsa_circ_0007823 in TNBC. Materials and Methods: Relative hsa_circ_0007823 levels in TNBC tissues and cell lines were examined by reverse transcription-quantitative polymerase chain reaction. The value of hsa_circ_0007823 levels was evaluated in patients' clinicopathological characteristics and prognostic prediction. A dual-luciferase reporter assay was used to determine the relationship between hsa_circ_0007823, miR-182-5p, and FOXO1. The effect of circ_0007823 overexpression on the growth of TNBC cells was investigated in vitro and in vivo. Results: Lower levels of hsa_circ_0007823 were found in TNBC tissues and cell lines and were closely associated with lymph node metastasis, poorer overall and disease-free survival rates. MiR-182-5p was significantly up-regulated, whereas FOXO1 was down-regulated in TNBC cell lines. The miR-182-5p inhibition up-regulated FOXO1 in TNBC cells. Dual-luciferase reporter assays showed that hsa_circ_0007823, miR-182-5p, and FOXO1 interacted with each other. Overexpression of circ_0007823 significantly inhibited the viability, migration, and invasion of TNBC cell lines, but promoted apoptosis. In vivo experiments showed that circ_0007823 overexpression inhibited tumor growth and down-regulated miR-182-5p and up-regulated FOXO1. Conclusion: Hsa_circ_0007823 overexpression could suppress the growth, invasion, and migration of TNBC cells, and inhibit tumor growth by regulating miR-182-5p/FOXO1.

circUSP42 Is Downregulated in Triple-Negative Breast Cancer and Associated With Poor Prognosis.

We previously showed that microRNA-182 (miR-182) might promote cell proliferation and migration in triple-negative breast cancer (TNBC). This study aimed to investigate circular RNAs (circRNAs) that interact with miR-182 and play important roles in TNBC. Thirty patients with TNBC were enrolled. One pair of tumor and adjacent tissue samples (control) were submitted for circRNA sequencing to establish the expression profile of circRNAs. Concomitantly, circRNAs aberrantly expressed between TNBC and control groups were identified, and these differentially expressed circRNAs (DEcircRNAs) were subjected to Gene Ontology and KEGG pathway enrichment analyses, as well as prediction of interactions with miRNAs. The expression levels of 5 circRNAs interacting with miR-182 were validated using qRT-PCR. Associations between the expression of circUSP42 and clinicopathological features and prognosis were evaluated. A total of 825 upregulated and 1127 downregulated DEcircRNAs were identified between tumor and control groups. Upregulated DEcircRNAs were significantly involved in proteoglycans in cancer, and endocytosis. Downregulated DEcircRNAs were involved in the pathway of resistance to EGFR tyrosine kinase inhibitors. Prediction of circRNA-miRNA interactions showed that hsa_circ_0002032, chr6:131973682-132047340+, hsa_circ_0005982, hsa_circ_0007823 (circUSP42), and hsa_circ_0001777 might act as miRNA sponges for miR-182. qRT-PCR showed consistent results with circRNA sequencing data (P < 0.05). Downregulation of circUSP42 was significantly associated with lymph node metastasis (P = 0.005) and advanced clinical stage (P = 0.032). Furthermore, Kaplan-Meier plots showed that low expression of circUSP42 was closely associated with poor outcome (log-rank test, P < 0.001). Our data suggested that dysregulation of circUSP42 might contribute to the development and progression of TNBC.

Metastasis suppressor 1 acts as a tumor suppressor by inhibiting epithelial-to-mesenchymal transition in triple-negative breast cancer.

OBJECTIVE: This study aimed to analyze the function of metastasis suppressor 1 (MTSS1) in triple negative breast cancer (TNBC). METHODS: MTSS1 expression in 30 TNBC and paracancerous tissues was measured by quantitative reverse transcriptase polymerase chain reaction. The prognostic value of MTSS1 was assessed by Kaplan-Meier analysis followed by the log-rank test. MCF7 cells were transfected with si-MTSS1, while MDA-MB-231 cells were transfected with pcDNA3.1-MTSS1. Cell proliferation assay and transwell assay were performed to investigate the effects of MTSS1 on the biological behavior of breast cancer cells. Immunofluorescence and western blot were used to detect the influence of MTSS1 on epithelial-mesenchymal transition (EMT) markers. RESULTS: MTSS1 expression was significantly lower in TNBC tissues compared with that in paracancerous tissues (0.012 vs. 0.370; P = 0.006). A lower MTSS1 expression level was also found in tumor tissues of patients with lymph node metastasis (P = 0.002) or tumor node metastasis stage (P = 0.010). Patients with low expression of MTSS1 (⩽ 0.009) had shorter disease-free survival (47.4 vs. 56.0 months; P = 0.012). The knockdown of MTSS1 in MCF7 cells inhibited cell proliferation, enhanced cell migration and invasion capacities, decreased the E-cadherin level, and increased the vimentin level, whereas overexpression of MTSS1 in MDA-MB-231 cells had the opposite effects (P < 0.05). CONCLUSIONS: Our findings demonstrated that MTSS1 regulates proliferation, invasion, migration, and EMT in TNBC, and that decreased MTSS1 is associated with shorter disease-free survival.