The effects of oenothein B(OEB) on the proliferation, apoptosis, invasion, and migration of breast cancer MCF-7 and MDA-MB-231 cells were investigated by cell culture in vitro, network pharmacology, and molecular docking. In vitro cell experiments revealed that OEB inhibited the proliferation and colony formation ability, and promoted the apoptosis and formation of apoptotic bodies in breast cancer cells, as well as inhibited the invasion and migration of breast cancer cells. The targets of OEB were obtained using SwissTargetPrediction database and breast cancer targets were obtained from GeneCards. The targets of OEB and breast cancer were entered separately in Venny 2.1 software to obtain the Venn diagram of common targets of OEB and breast cancer. The common targets of OEB and breast cancer were input into STRING database to construct a protein-protein interaction(PPI) network, which was entered into Cytoscape 3.7.2 software for network topology analysis. Key targets were screened according to protein association strength, and analyzed for KEGG pathway enrichment. Molecular docking of OEB to key targets using AutoDock software revealed that OEB stably bound to the active pocket of P53, while OEB promoted the expression of P53 protein. MCF-7 and MDA-MB-231 cell viability and migration ability increased after silencing P53, and this change was reversed after treatment with OEB. Therefore, this study showed that OEB inhibited the proliferation, migration, and invasion of breast cancer MCF-7 and MDA-MB-231 cells, and promoted the apoptosis of breast cancer MCF-7 and MDA-MB-231 cells, which may be related to the targeted regulation of P53.
Humans ; Female ; Cell Proliferation ; Breast Neoplasms/drug therapy* ; Tumor Suppressor Protein p53/genetics* ; Molecular Docking Simulation

BACKGROUND: Breast cancer patients who are positive for hormone receptor typically exhibit a favorable prognosis. It is controversial whether chemotherapy is necessary for them after surgery. Our study aimed to establish a multigene model to predict the relapse of hormone receptor-positive early-stage Chinese breast cancer after surgery and direct individualized application of chemotherapy in breast cancer patients after surgery. METHODS: In this study, differentially expressed genes (DEGs) were identified between relapse and nonrelapse breast cancer groups based on RNA sequencing. Gene set enrichment analysis (GSEA) was performed to identify potential relapse-relevant pathways. CIBERSORT and Microenvironment Cell Populations-counter algorithms were used to analyze immune infiltration. The least absolute shrinkage and selection operator (LASSO) regression, log-rank tests, and multiple Cox regression were performed to identify prognostic signatures. A predictive model was developed and validated based on Kaplan-Meier analysis, receiver operating characteristic curve (ROC). RESULTS: A total of 234 out of 487 patients were enrolled in this study, and 1588 DEGs were identified between the relapse and nonrelapse groups. GSEA results showed that immune-related pathways were enriched in the nonrelapse group, whereas cell cycle- and metabolism-relevant pathways were enriched in the relapse group. A predictive model was developed using three genes ( CKMT1B , SMR3B , and OR11M1P ) generated from the LASSO regression. The model stratified breast cancer patients into high- and low-risk subgroups with significantly different prognostic statuses, and our model was independent of other clinical factors. Time-dependent ROC showed high predictive performance of the model. CONCLUSIONS A multigene model was established from RNA-sequencing data to direct risk classification and predict relapse of hormone receptor-positive breast cancer in Chinese patients. Utilization of the model could provide individualized evaluation of chemotherapy after surgery for breast cancer patients.
Humans ; Female ; Breast Neoplasms/genetics* ; East Asian People ; Neoplasm Recurrence, Local/genetics* ; Breast ; Algorithms ; Chronic Disease ; Prognosis ; Tumor Microenvironment

Objective: To investigate the pathological features and the clinicopathological significance of TERT detection in those tumors that were difficult to diagnosis. Methods: A total of 93 cases of fibroepithelial tumors without definite diagnosis were collected from the Affiliated Hospital of Qigndao University between 2013 and 2021. The clinical details such as patients' age and tumor size were collected. All slides were re-reviewed and the pathologic parameters, including stromal cellularity, stromal cell atypia, stromal cell mitoses, and stromal overgrowth were re-interpreted. Sanger sequencing was used to detect TERT promoter status, and immunohistochemistry was performed to detect TERT protein expression. The relationship between TERT promoter mutation as well as protein expression levels and the clinicopathological parameters were also analyzed. Results: The patients' ages ranged from 30 to 71 years (mean of 46 years); the tumor size ranged from 1.2 to 8.0 cm (mean 3.8 cm). These tumors showed the following morphologic features: leafy structures in the background of fibroadenoma, or moderately to severely abundant stromal cells. The interpretations of tumor border status were ambiguous in some cases. The incidence of TERT promoter mutation was high in patients of age≥50 years, tumor size≥4 cm, and stromal overgrowth at ×4 or ×10 objective, and these clinicopathologic features were in favor of diagnosis of phyllodes tumors. TERT protein expression levels was not associated with the above clinicopathologic parameters and its promoter mutation status. Conclusions: The diagnostic difficulty for the breast fibroepithelial tumors is due to the difficulty in recognition of the leafy structures or in those cases with abundant stromal cells. A comprehensive evaluation combined with morphologic characteristics and molecular parameters such as TERT promoter may be helpful for the correct diagnosis and better evaluating recurrence risk.
Humans ; Adult ; Middle Aged ; Aged ; Female ; Neoplasms, Fibroepithelial/pathology* ; Phyllodes Tumor/genetics* ; Stromal Cells ; Fibroadenoma/pathology* ; Breast Neoplasms/pathology* ; Mutation ; Telomerase/genetics*

Humans ; Female ; Breast Neoplasms/pathology* ; Multiomics ; Trastuzumab ; Receptor, ErbB-2/genetics* ; Machine Learning

Humans ; Female ; Breast Neoplasms/genetics* ; Prognosis ; Gene Expression Profiling ; Biomarkers, Tumor/genetics* ; Gene Expression Regulation, Neoplastic/genetics* ; Receptor, ErbB-2/metabolism* ; Gene Regulatory Networks/genetics*

Humans ; Female ; MicroRNAs/genetics* ; Breast Neoplasms/genetics* ; Point-of-Care Systems ; Early Detection of Cancer ; Gene Expression Regulation, Neoplastic

The estimated new cases of breast cancer (BC) patients were 2.26 million in 2020, which accounted for 11.7% of all cancer patients, making it the most prevalent cancer worldwide. Early detection, diagnosis and treatment are crucial to reduce the mortality, and improve the prognosis of BC patients. Despite the widespread use of mammography screening as a tool for BC screening, the false positive, radiation, and overdiagnosis are still pressing issues that need to be addressed. Therefore, it is urgent to develop accessible, stable, and reliable biomarkers for non-invasive screening and diagnosis of BC. Recent studies indicated that the circulating tumor cell DNA (ctDNA), carcinoembryonic antigen (CEA), carbohydrate antigen 15-3 (CA15-3), extracellular vesicles (EV), circulating miRNAs and BRCA gene from blood, and the phospholipid, miRNAs, hypnone and hexadecane from urine, nipple aspirate fluid (NAF) and volatile organic compounds (VOCs) in exhaled gas were closely related to the early screening and diagnosis of BC. This review summarizes the advances of the above biomarkers in the early screening and diagnosis of BC.
Humans ; Female ; Biomarkers, Tumor ; Early Detection of Cancer ; Breast Neoplasms/diagnosis* ; Prognosis ; MicroRNAs/genetics*

Breast cancer is a malignant tumor that seriously endangers women's lives. The prognosis of breast cancer patients differs among molecular types. Compared with other subtypes, triple-negative breast cancer (TNBC) has been a research hotspot in recent years because of its high degree of malignancy, strong invasiveness, rapid progression, easy of recurrence, distant metastasis, poor prognosis, and high mortality. Many studies have found that long non-coding RNA (lncRNA) plays an important role in the occurrence, proliferation, migration, recurrence, chemotherapy resistance, and other characteristics of TNBC. Some lncRNAs are expected to become biomarkers in the diagnosis and prognosis of TNBC, and even new targets for its treatment. Based on a PubMed literature search, this review summarizes the progress in research on lncRNAs in TNBC and discusses their roles in TNBC diagnosis, prognosis, and chemotherapy with the hope of providing help for future research.
Humans ; Female ; Triple Negative Breast Neoplasms/genetics* ; RNA, Long Noncoding/genetics* ; Biomarkers, Tumor/genetics* ; Gene Expression Regulation, Neoplastic

The characteristic genetic abnormality of neuroendocrine neoplasms (NENs), a heterogeneous group of tumors found in various organs, remains to be identified. Here, based on the analysis of the splicing variants of an oncogene Focal Adhesion Kinase (FAK) in The Cancer Genome Atlas datasets that contain 9193 patients of 33 cancer subtypes, we found that Box 6/Box 7-containing FAK variants (FAK^6/7) were observed in 7 (87.5%) of 8 pancreatic neuroendocrine carcinomas and 20 (11.76%) of 170 pancreatic ductal adenocarcinomas (PDACs). We tested FAK variants in 157 tumor samples collected from Chinese patients with pancreatic tumors, and found that FAK^6/7 was positive in 34 (75.6%) of 45 pancreatic NENs, 19 (47.5%) of 40 pancreatic solid pseudopapillary neoplasms, and 2 (2.9%) of 69 PDACs. We further tested FAK splicing variants in breast neuroendocrine carcinoma (BrNECs), and found that FAK^6/7 was positive in 14 (93.3%) of 15 BrNECs but 0 in 23 non-NEC breast cancers. We explored the underlying mechanisms and found that a splicing factor serine/arginine repetitive matrix protein 4 (SRRM4) was overexpressed in FAK^6/7-positive pancreatic tumors and breast tumors, which promoted the formation of FAK^6/7 in cells. These results suggested that FAK^6/7 could be a biomarker of NENs and represent a potential therapeutic target for these orphan diseases.
Female ; Humans ; Alternative Splicing ; Breast Neoplasms/metabolism* ; Carcinoma, Pancreatic Ductal/pathology* ; Focal Adhesion Protein-Tyrosine Kinases/therapeutic use* ; Nerve Tissue Proteins/genetics* ; Neuroendocrine Tumors/genetics* ; Oncogenes ; Pancreatic Neoplasms/metabolism*

BACKGROUND: Observational research has reported that systemic lupus erythematosus (SLE) is related to common female hormone-dependent cancers, but the underlying causal effect remains undefined. This study aimed to explore the causal association of these conditions by Mendelian randomization (MR) analysis. METHODS: We selected instrumental variables for SLE from genome-wide association studies (GWASs) conducted in European and East Asian populations. The genetic variants for female malignant neoplasms were obtained from corresponding ancestry GWASs. We utilized inverse variance weighted (IVW) as the primary analysis, followed by sensitivity analysis. Furthermore, we conducted multivariable MR (MVMR) to estimate direct effects by adjusting for the body mass index and estradiol. Finally, we implemented reverse direction MR analysis and gave a negative example to test the reliability of MR results. RESULTS: We found SLE was significantly negatively associated with overall endometrial cancer risk (odds ratio [OR] = 0.961, 95% confidence interval [CI] = 0.935-0.987, P  = 3.57E-03) and moderately inversely related to endometrioid endometrial cancer (ENEC) (OR = 0.965, 95% CI = 0.936-0.995, P  = 0.024) risk in the European population by IVW. We replicated these results using other MR models and detected a direct effect by MVMR (overall endometrial cancer, OR = 0.962, 95% CI = 0.941-0.983, P  = 5.11E-04; ENEC, OR = 0.964, 95% CI = 0.940-0.989, P  = 0.005). Moreover, we revealed that SLE was correlated with decreased breast cancer risk (OR = 0.951, 95% CI = 0.918-0.986, P  = 0.006) in the East Asian population by IVW, and the effect was still significant in MVMR (OR = 0.934, 95% CI = 0.859-0.976, P  = 0.002). The statistical powers of positive MR results were all >0.9. CONCLUSION This finding suggests a possible causal effect of SLE on the risk of overall endometrial cancer and breast cancer in European and East Asian populations, respectively, by MR analysis, which compensates for inherent limitations of observational research.
Female ; Humans ; Genome-Wide Association Study ; Mendelian Randomization Analysis ; Neoplasms, Hormone-Dependent ; Reproducibility of Results ; Endometrial Neoplasms ; Lupus Erythematosus, Systemic/genetics* ; Carcinoma, Endometrioid ; Breast Neoplasms ; Polymorphism, Single Nucleotide