Breast cancer is the most common malignant tumor and the main cause of cancer-associated mortality in females worldwide. Long non-coding RNAs (lncRNAs) have been reported to play vital roles in breast cancer development and progression; however, our understanding of most lncRNAs in breast cancer is still limited. In this study, we demonstrated that small nucleolar RNA host gene 5 (SNHG5) promotes breast cancer cell proliferation both in vitro and in vivo , and depletion of SNHG5 significantly led to cell-cycle arrest at G1 phase. Accumulating evidence has shown that many lncRNA transcripts could function as competing endogenous RNAs (ceRNAs) by competitively binding common microRNAs (miRNAs). We found that SNHG5 acts as a sponge for miR-154-5p, reducing its ability to repress proliferating cell nuclear antigen (PCNA). SNHG5 promoted breast cancer proliferation and cell-cycle progression by upregulation of PCNA expression. Clinically, we observed an increased SNHG5 expression in breast cancer, whereas miR-154-5p was decreased in breast cancer tissues compared with the adjacent normal breast tissues. Furthermore, the SNHG5 expression was significantly negatively correlated with miR-154-5p expression. Taken together, our data uncover the SNHG5-miR-154-5p-PCNA axis and provide a novel mechanism to explain breast cancer proliferation.

Background: Triple-negative breast cancer (TNBC) is a special subtype of breast cancer with poor prognosis. DNA damage response (DDR) is one of the hallmarks of this cancer. However, the association of DDR genes with the prognosis of TNBC is still unclear.Methods: We identified differentially expressed genes (DEGs) between normal and TNBC samples from The Cancer Genome Atlas (TCGA). DDR genes were obtained from the Molecular Signatures Database through six DDR gene sets. After the expression of six differential genes were verified by quantitative real-time polymerase chain reaction (qRT-PCR), we then overlapped the DEGs with DDR genes. Based on univariate and LASSO Cox regression analyses, a prognostic model was constructed to predict overall survival (OS). Kaplan–Meier analysis and receiver operating characteristic curve were used to assess the performance of the prognostic model. Cox regression analysis was applied to identify independent prognostic factors in TNBC. The Human Protein Atlas was used to study the immunohistochemical data of six DEGs. The prognostic model was validated using an independent dataset. Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes analysis were performed by using gene set enrichment analysis (GSEA). Single-sample gene set enrichment analysis was employed to estimate immune cells related to this prognostic model. Finally, we constructed a transcriptional factor (TF) network and a competing endogenous RNA regulatory network.Results: Twenty-three differentially expressed DDR genes were detected between TNBC and normal samples. The six-gene prognostic model we developed was shown to be related to OS in TNBC using univariate and LASSO Cox regression analyses. All the six DEGs were identified as significantly up-regulated in the tumor samples compared to the normal samples in qRT-PCR. The GSEA analysis indicated that the genes in the high-risk group were mainly correlated with leukocyte migration, cytokine interaction, oxidative phosphorylation, autoimmune diseases, and coagulation cascade. The mutation data revealed the mutated genes were different. The gene-TF regulatory network showed that Replication Factor C subunit 4 occupied the dominant position.Conclusion: We identified six gene markers related to DDR, which can predict prognosis and serve as an independent biomarker for TNBC patients.

BackgroundTo investigate the occurrence of catheter malposition in breast cancer patients undergoing Totally Implantable Venous Access Port (TIVAP) implantation and analyze the effect of TIVAP implantation site on the incidence of catheter malposition.MethodsClinical data of Breast cancer patients underwent TIVAP implantation in our department from 2017 to 2021 was collected by reviewing the electronic medical records. The catheter malposition rate, location and management of malposed catheters in TIVAP implantation were analyzed. We divided the patients into the left internal jugular vein (IJV) group and the right IJV group according to the site of TIVAP implantation and compared the difference in the catheter malposition incidence between the two groups. In addition, we counted the catheter malposition rate of TIVAP implantion via the left and right IJV in right breast cancer patients to analyze the effect of tumor status on the side of TIVAP implantation on the catheter malposition rate.ResultsA total of 1,510 catheters were implanted in 1,504 patients, and 16 (1.06%) had catheter malposition. The catheter malposition rate was 4.96% (7/141) for TIVAP implanted via the left IJV and 0.66% (9/1,369) for right IJV, with a statistically significant difference (χ2 = 18.699, P < 0.05). 743 TIVAPs were implanted in patients with right-sided breast tumor, of which the incidence of catheter malposition was 5.15% (7/136) for TIVAP implanted via left IJV and 0.82% (5/607) for right IJV, with a statistically significant difference (χ2 = 10.290, P < 0.05). Malposed catheters were found in the subclavian vein, IJV, brachiocephalic vein, internal thoracic vein, undefined collateral veins, and outside the blood vessels. All malposed catheters were successfully adjusted to the proper position by simple manipulative repositioning or percutaneous positioning with the assistance of digital subtraction angiography (DSA), except for 1 case was removed the port because the catheter tip was located outside the vessel.ConclusionThe catheter malposition rate of ultrasound-guided TIVAP implantation via IJV is low, and the malposed catheter can be successfully adjusted to the proper position by simple manipulative repositioning or DSA-assisted percutaneous positioning, however, the catheter malposition incidence of TIVAP implanted via left IJV is higher than that via the right side.

Ferroptosis is a type of cell regulated necrosis triggered by intracellular phospholipid peroxidation, which is more immunogenic than apoptosis. Therefore, genes controlling ferroptosis may be promising candidate biomarkers for tumor therapy. In this study, we investigate the function of genes associated with ferroptosis in breast cancer (BC) and systematically evaluate the relationship between ferroptosis-related gene expression and prognosis of BC patients from the Cancer Genome Atlas database. By using the consensus clustering method, 1203 breast cancer samples were clustered into two clearly divided subgroups based on the expression of 237 ferroptosis-related genes. Then differentially expressed analysis and least absolute shrinkage and selection operator were used to identify the prognosis-related genes. Furthermore, the genetic risk signature was constructed using the expression of prognosis-related genes. Our results showed that the genetic risk signature can identify patient subgroups with distinct prognosis in either training cohort or validation, and the genetic risk signature was associated with the tumor immune microenvironment. Finally, the Cox regression analysis indicated that our risk signature was an independent prognostic factor for BC patients and this signature was verified by the polymerase chain reaction and western blot. Within this study, we identified a novel prognostic classifier based on five ferroptosis-related genes which may provide a new reference for the treatment of BRCA patients.

BackgroundBreast cancer (BC) is the most common tumor to develop cutaneous metastases. Most BCs with cutaneous metastasis are human epidermal growth factor receptor 2 (HER2)-positive subtypes. Although the molecular mechanisms of breast cancer metastasis to different sites and the corresponding treatment methods are areas of in-depth research, there are few studies on cutaneous metastasis.Case PresentationFive HER2-positive BC patients with extensive cutaneous metastases were treated with a regimen containing pyrotinib, a novel small-molecule tyrosine kinase inhibitor that irreversibly blocks epidermal growth factor receptor (EGFR), HER2, and human epidermal growth factor receptor 4 (HER4), then their cutaneous metastases quickly resolved at an astonishing speed and their condition was well controlled during the follow-up period.ConclusionsThis case series reports the significant therapeutic effect of pyrotinib on cutaneous metastases of HER2-positive BC for the first time. Based on this, we recommend that pyrotinib can be used as a supplement to trastuzumab for HER2-positive BC patients with cutaneous metastases. In addition, we should consider that the pan-inhibitory effect of pyrotinib on EGFR, HER2, and HER4 may provide a dual therapeutic effect against HER2 and mucin 1.

Background The changes of lipid metabolism have been implicated in the development of many tumors, but its role in breast invasive carcinoma (BRCA) remains to be fully established. Here, we attempted to ascertain the prognostic value of lipid metabolism-related genes in BRCA. Methods We obtained RNA expression data and clinical information for BRCA and normal samples from public databases and downloaded a lipid metabolism-related gene set. Ingenuity Pathway Analysis (IPA) was applied to identify the potential pathways and functions of Differentially Expressed Genes (DEGs) related to lipid metabolism. Subsequently, univariate and multivariate Cox regression analyses were utilized to construct the prognostic gene signature. Functional enrichment analysis of prognostic genes was achieved by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Kaplan-Meier analysis, Receiver Operating Characteristic (ROC) curves, clinical follow-up results were employed to assess the prognostic potency. Potential compounds targeting prognostic genes were screened by Connectivity Map (CMap) database and a prognostic gene-drug interaction network was constructed using Comparative Toxicogenomics Database (CTD). Furthermore, we separately validated the selected marker genes in BRCA samples and human breast cancer cell lines (MCF-7, MDA-MB-231). Results IPA and functional enrichment analysis demonstrated that the 162 lipid metabolism-related DEGs we obtained were involved in many lipid metabolism and BRCA pathological signatures. The prognostic classifier we constructed comprising SDC1 and SORBS1 can serve as an independent prognostic marker for BRCA. CMap filtered 37 potential compounds against prognostic genes, of which 16 compounds could target both two prognostic genes were identified by CTD. The functions of the two prognostic genes in breast cancer cells were verified by cell function experiments. Conclusion Within this study, we identified a novel prognostic classifier based on two lipid metabolism-related genes: SDC1 and SORBS1 . This result highlighted a new perspective on the metabolic exploration of BRCA.

Ferroptosis is a non-small molecule-induced form of tumor cell apoptosis, which has been shown to regulate the biological behavior of tumors. Therefore, genes controlling ferroptosis may be promising candidate biomarkers for tumor therapy. In this study, we investigate the function of genes associated with ferroptosis in breast cancer (BC) and systematically evaluate the relationship between ferroptosis-related gene expression profiles and prognosis in BC patients based on the Cancer Genome Atlas RNA-sequencing dataset (TCGA). By using the non-negative matrix factorization clustering method, 1,203 breast cancer samples were clustered into two clearly divided subgroups based on the expression of 237 ferroptosis-related genes. The least absolute shrinkage and selection operator (LASSO) was used to develop risk profiles for five genes, and then these five genes were verified by the polymerase chain reaction (PCR). The relationship between genetic risk characteristics and clinical characteristics of BC is described. The results show that the genetic risk signature associated with clinical characteristics can be used as independent prognostic indicators for BC patients.

No abstract