Background: Breast cancer (BC) is one of the most prevalent malignant tumours that threatens women health worldwide. It has been reported that circular RNAs (circRNAs) play an important role in regulating tumour progression and tumour microenvironment (TME) remodelling.Methods: Differentially expression characteristics and immune correlations of circRNAs in BC were verified using high‐throughput sequencing and bioinformatic analysis. Exosomes were characterised by nanoparticle transmission electron microscopy and tracking analysis. The biological function of circ‐0100519 in BC development was demonstrated both in vitro and in vivo. Western blotting, RNA pull‐down, RNA immunoprecipitation, flow cytometry, and luciferase reporter were conducted to investigate the underlying mechanism.Results: Circ‐0100519 was significant abundant in BC tumour tissues and related to poor prognosis. It can be encapsulated into secreted exosomes, thereby promoting BC cell invasion and metastasis via inducing M2‐like macrophages polarisation.Mechanistically, circ‐0100519 acted as a scaffold to enhance the interaction between the deubiquitinating enzyme ubiquitin‐specific protease 7 (USP7) and nuclear factor‐like 2 (NRF2) in macrophages, inducing the USP7‐mediated deubiquitination of NRF2. Additionally, HIF‐1α could function as an upstream effector to enhance circ‐0100519 transcription.Conclusions: Our study revealed that exosomal circ‐0100519 is a potential biomarker for BC diagnosis and prognosis, and the HIF‐1α inhibitor PX‐478 may provide a therapeutic target for BC.

Breast cancer (BRCA) has become the highest incidence of cancer due to its heterogeneity. To predict the prognosis of BRCA patients, sensitive biomarkers deserve intensive investigation. Herein, we explored the role of N⁶-methyladenosine-related long non-coding RNAs (m⁶A-related lncRNAs) as prognostic biomarkers in BRCA patients acquired from The Cancer Genome Atlas (TCGA; n = 1,089) dataset and RNA sequencing (RNA-seq) data (n = 196). Pearson’s correlation analysis, and univariate and multivariate Cox regression were performed to select m⁶A-related lncRNAs associated with prognosis. Twelve lncRNAs were identified to construct an m⁶A-related lncRNA prognostic signature (m⁶A-LPS) in TCGA training (n = 545) and validation (n = 544) cohorts. Based on the 12 lncRNAs, risk scores were calculated. Then, patients were classified into low- and high-risk groups according to the median value of risk scores. Distinct immune cell infiltration was observed between the two groups. Patients with low-risk score had higher immune score and upregulated expressions of four immune-oncology targets (CTLA4, PDCD1, CD274, and CD19) than patients with high-risk score. On the contrary, the high-risk group was more correlated with overall gene mutations, Wnt/β-catenin signaling, and JAK-STAT signaling pathways. In addition, the stratification analysis verified the ability of m⁶A-LPS to predict prognosis. Moreover, a nomogram (based on risk score, age, gender, stage, PAM50, T, M, and N stage) was established to evaluate the overall survival (OS) of BRCA patients. Thus, m⁶A-LPS could serve as a sensitive biomarker in predicting the prognosis of BRCA patients and could exert positive influence in personalized immunotherapy.

Background: Breast cancer is becoming a tumor with the highest morbidity rate, and inflammation-induced cell death namely pyroptosis reportedly plays dual roles in cancers. However, the specific mechanism between pyroptosis and the clinical prognosis of breast cancer patients is indistinct. Hence, novel pyroptosis-related biomarkers and their contributing factors deserve further exploration to predict the prognosis in breast cancer.Methods: Pearson’s correlation analysis, and univariate and multivariate Cox regression analysis were utilized to obtain six optimal pyroptosis-related gene prognostic signatures (Pyro-GPS). The risk score of each breast cancer patient was calculated. Next, a Pyro-GPS risk model was constructed and verified in TCGA cohort (n=1,089) and GSE20711 cohort (n=88). Then analyses of immune microenvironment, genomic variation, functional enrichment, drug response and clinicopathologic feature stratification associated with the risk score of Pyro-GPS were performed. Subsequently, a nomogram based on the risk score and several significant clinicopathologic features was established. Ultimately, we further investigated the role of CCL5 in the biological behavior of MDA-MB-231 cell line.Results: The low-risk breast cancer patients have better survival outcomes than the high-risk patients. The low-risk patients also show higher immune cell infiltration levels and immune-oncology target expression levels. There is no significant difference in genetic variation between the two risk groups, but the frequency of gene mutations varies. Functional enrichment analysis shows that the low-risk patients are prominently correlated with immune-related pathways, whereas the high-risk patients are enriched in cell cycle, ubiquitination, mismatch repair, homologous recombination and biosynthesis-related pathways. Pyro-GPS is positively correlated with the IC50 of anti-tumor drugs. Furthermore, comprehensive analyses based on risk score and clinicopathological features were performed to predict the prognosis of breast cancer patients. Additionally, in vitro experiments confirmed that breast cancer cells with high expression of CCL5 had weaker proliferation, invasion and metastasis abilities as well as stronger apoptosis and cell cycle arrest abilities.Conclusions: The risk score of Pyro-GPS can serve as a promising hallmark to predict the prognosis of BRCA patients. Risk score evaluation may assist to acquire relevant information of tumor immune microenvironment, genomic mutation status, functional pathways and drug sensitivity, and thus provide more effective personalized strategies.

Purpose The aim of this study was to compare the outcomes of laparoscopic appendectomy (LA) using purse string invaginating sutures (PS) with those using intracorporeal knotting (IK) or Hem-o-lock polymeric clips (HL). Methods A total of 882 patients who underwent laparoscopic appendectomy from January 2015 to December 2017 were studied retrospectively. Of these, 538 patients used PS, 229 patients used IK and 115 patients used HL to close the appendiceal stump. Their demographic characteristics, intraoperative findings and postoperative complications were analysed retrospectively. Results There were similar percentages of complicated cases in all the groups (21.7% in PS vs. 21.4% in IK vs. 24.3% in HL, p = 0.803). The mean length of hospital stay was shorter in PS group when compared to IK or HL group (3.72 + 2.35 in PS vs. 4.41 + 2.40 in IK, 4.43 + 2.66 in HL, p < 0.05) as well as lower ASA scores (1.7 + 0.6 in PS vs. 1.8 + 0.6 in IK vs. 1.7 + 0.6 in HL, p < 0.05). The overall complication rates for the PS, the HL and the IK groups were 12.1, 8.7 and 9.2%, respectively. The rate of wound infection was higher in PS group for uncomplicated appendicitis (5.0% in PS vs. 2.8% in IK and 1.1% in HL, p = 0.129). Furthermore, there were no differences in the rate of intra-abdominal infection among the groups in both uncomplicated and complicated cases. Conclusions Based on our results, purse string suture failed to demonstrate better postoperative outcome in laparoscopic appendectomy and is no longer recommended by our institution as initial approach.

Worldwide, breast cancer is the most common malignancy. LHX2, a member of the LIM homeobox gene family and a transcription factor, plays a crucial role in numerous tumors, but the function of LHX2 in breast cancer progression remains unknown. In this study, we show that LHX2 is upregulated in breast cancer tissues and positively correlated with breast cancer progression. Meanwhile, the clinical characteristics of breast cancer and LHX2 expression showed a strong correlation. GSEA showed that a high LHX2 expression may activate the T-cell activation pathway, PI3K/AKT/mTOR signaling pathway, and apoptosis pathway. Moreover, ssGSEA showed that Th1 cells and Th2 cells had a positive correlation with LHX2 expression in breast cancer. Experiments showed that LHX2 promotes the proliferation, colony formation, migration, and invasion of breast cancer cells. Immunohistochemistry and immunofluorescence assays helped to analyze LHX2-associated immune infiltration in breast cancer. A Western blot assay proved that LHX2 activated the PI3K/AKT/mTOR pathway and the apoptosis pathway. A TUNEL assay confirmed that LHX2 inhibited apoptosis. Taken together, LHX2 plays a vital role in breast cancer’s progression and prognosis and could be an immune infiltration biomarker for breast cancer, and LHX2 activates the PI3K/AKT/mTOR pathway and apoptosis pathway in breast cancer.

Breast cancer (BRCA) is the most fatal malignancy of women. Immunotherapy has greatly improved the prognosis of advanced BRCA. Cellular senescence contributes to tumorigenesis and suppresses anti-cancer immunity. Identification of senescence-relevant long noncoding RNAs (SRlncRNAs) signature may benefit the predictions of prognosis and response to immunotherapy of BRCA. RNA-seq, mutation, and clinical data of BRCA were acquired from public databases. SRlncRNAs were screened using univariate Cox regression analysis. Consensus clustering classified BRCA patients into 2 clusters, and the differences of overall survival (OS) and immune status between the 2 clusters were analyzed by survival analysis, CIBERSORT, and ESITIMATE. The SRlncRNAs signature was constructed by least absolute shrinkage and selection operator (LASSO) regression analysis, and BRCA patients were divided into 2 risk groups. Enrichment analyses were performed to explore the cancer- and immunotherapy-relevant pathways. Transcriptome analysis was performed to investigate the differences of OS, immune infiltration, and ESITIMATE score of the 2 groups. Genome analysis was applied to investigate the differences of somatic mutation, tumor mutation burden (TMB) and microsatellite instability (MSI) between the 2 risk groups. A nomogram combined with calibration curves and decision curve analysis (DCA) was established for better clinical decision. Tumor Immune Dysfunction and Exclusion (TIDE) score and IMvigor-210 were applied for the predicting of response to immunotherapy. Profiling Relative Inhibition Simultaneously in Mixtures (PRISM) and the Cancer Therapeutics Response Portal resource (CTRP) databases were used for drug susceptibility analysis. Ten prognostic SRlncRNAs were identified and BRCA patients were divided into 2 clusters. Cluster 1 had better OS with anti-tumor immune microenvironment. The high-risk BRCA had poorer OS in the Cancer Genome Atlas (TCGA) training cohort, which was also verified by TCGA validation cohort and GSE20685 validation cohort. Low-risk patients also had anti-tumor immune microenvironment. Genome analysis demonstrated that the high-risk group had significant higher TMB. High-risk BRCA were more susceptive to immunotherapy according to the TIDE score and IMvigor-210. Finally, drug susceptibility analysis showed that 6 compounds were sensitive to high-risk BRCA patients. We developed and verified an original SRlncRNAs signature by multi-omics analysis, which could serve as a prognosis and immunotherapy predictor for BRCA.