ABSTRACT
CircRNAs (circular RNA) are reported to regulate onset and progress multiple cancers. Nonetheless, the function along with the underlying mechanisms of circRNAs in HER-2-positive breast cancer (BC) remains unclear. CircRNA microarrays were performed to elucidate expression profiles of HER-2-positive BC cells. circRNA levels were quantified using qRT-PCR assay. Various in vitro along with in vivo assays were employed to further explore the effects of circGFRA1 in the progress of HER-2-positive BC and interactions of circGFRA1, miR-1228 and AIFM2 in Her-2-positive BC. CircGFRA1 was remarkably upregulated in HER-2-positive BC. Knockdown of circGFRA1 could attenuate HER-2-positive BC progression by inhibiting the proliferation, infiltration and migratory ability of HER-2-positive BC cells. Through ceRNA mechanism, circGFRA1 could bind to miR-1228 and alleviate inhibitory activity of miR-1228 on targeted gene AIFM2. In summary, circGFRA1-miR-1228-AIFM2 axis regulates HER-2-positive BC. CircGFRA1 is a novel promising treatment option for HER-2-positive BC.
Subject(s)
Apoptosis Regulatory Proteins/genetics , Breast Neoplasms/genetics , Glial Cell Line-Derived Neurotrophic Factor Receptors/genetics , MicroRNAs/genetics , Mitochondrial Proteins/genetics , RNA, Circular/genetics , Receptor, ErbB-2/genetics , Animals , Apoptosis/genetics , Biomarkers, Tumor , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cell Line, Tumor , Disease Models, Animal , Female , Ferroptosis , Gene Expression Regulation, Neoplastic , Gene Silencing , Humans , Mice , RNA Interference , Receptor, ErbB-2/metabolismABSTRACT
Background: Systemic inflammatory response is related to the occurrence, progression, and prognosis of cancers. In this research, a novel systemic inflammation response score (SIRS) was calculated, and its prognostic value for postoperative stage I-III breast cancer (BC) patients was analyzed. Methods: 1583 BC patients were included in this research. Patients were randomly divided into a training cohort (n = 1187) and validation cohort (n = 396). SIRS was established in the training cohort based on independent prognostic hematological indicator, its relationship between prognosis and clinical features was analyzed. Then, a nomogram consisted of SIRS and clinical features was established, its performance was examined by calibration plots and receiver operating characteristic curve analysis. Results: The SIRS was an independent prognostic indicator for BC patients, and a high-SIRS was related to multifocality, advanced N stage, and worse prognosis. Incorporating SIRS into a nomogram could accurately predict the prognosis of BC patients, the results of receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) of nomogram was up to 0.806 in training cohort and 0.905 in the validation cohort. Conclusion: SIRS was associated with the prognosis of patients with breast cancer. Nomogram based on SIRS can accurately predict the prognosis of breast cancer patients.
ABSTRACT
AIMS: The purpose of this study was to investigate the potential correlation between metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and the transcription factor BTB and CNC homology 1 (BACH1) and their clinicopathological significance in triple-negative breast cancer (TNBC). SUBJECTS AND METHODS: MALAT1 and BACH1 were detected by immunohistochemistry using TNBC tissue microarrays of 240 patients. The association between MALAT1 and BACH1 expression levels was statistically analyzed. Moreover, the prognostic roles as well as clinical and pathological significance of MALAT1 and BACH1 expression in TNBC were determined. STATISTICAL ANALYSIS USED: Two-tailed Pearson correlation was used to examine the correlation of BACH1 and MALA1 expression. Comparisons of clinicopathological variables between different BACH1 and MALA1 expression groups were performed using χ2 tests. Overall survival (OS) and disease-free survival (DFS) curves were plotted with the Kaplan-Meier method and the differences in OS and DFS between three groups were compared by the log-rank test. Multiple comparisons were performed using χ2 tests for subsequent individual group comparisons. RESULTS: MALAT1 and BACH1 expression was significantly correlated with tumor-node-metastasis stage, distant metastasis, pathological stage, and survival outcomes of patients. Patients with high MALAT1 and BACH1 expression exhibited shorter overall survival and disease-free survival. CONCLUSIONS: These findings provide further insight into the expression pattern of MALAT1 and BACH1 in TNBC and suggest them as prognostic biomarkers for TNBC.
