RARRES2 regulates lipid metabolic reprogramming to mediate the development of brain metastasis in triple negative breast cancer

Background Triple negative breast cancer(TNBC),the most aggressive subtype of breast cancer,is characterized by a high incidence of brain metastasis(BrM)and a poor prognosis.As the most lethal form of breast cancer,BrM remains a major clinical challenge due to its rising incidence and lack of effective treatment strategies.Recent evidence suggested a potential role of lipid metabolic reprogramming in breast cancer brain metastasis(BCBrM),but the underlying mechanisms are far from being fully elucidated.Methods Through analysis of BCBrM transcriptome data from mice and patients,and immunohistochemical validation on patient tissues,we identified and verified the specific down-regulation of retinoic acid receptor responder 2(RARRES2),a multifunctional adipokine and chemokine,in BrM of TNBC.We investigated the effect of aberrant RARRES2 expression of BrM in both in vitro and in vivo studies.Key signaling pathway components were evaluated using multi-omics approaches.Lipidomics were performed to elucidate the regulation of lipid metabolic reprogramming of RARRES2.Results We found that downregulation of RARRES2 is specifically associated with BCBrM,and that RARRES2 deficiency promoted BCBrM through lipid metabolic reprogramming.Mechanistically,reduced expression of RARRES2 in brain metastatic potential TNBC cells resulted in increased levels of glycerophospholipid and decreased levels of triacylglycerols by regulating phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway to facilitate the survival of breast cancer cells in the unique brain microenvironment.Conclusions Our work uncovers an essential role of RARRES2 in linking lipid metabolic reprogramming and the development of BrM.RARRES2-dependent metabolic functions may serve as potential biomarkers or therapeutic targets for BCBrM.

Local dose-dense chemotherapy for triple-negative breast cancer via minimally invasive implantation of 3D printed devices

Dose-dense chemotherapy is the preferred first-line therapy for triple-negative breast cancer(TNBC),a highly aggressive disease with a poor prognosis.This treatment uses the same drug doses as conventional chemotherapy but with shorter dosing intervals,allowing for promising clinical outcomes with intensive treatment.However,the frequent systemic administration used for this treatment results in systemic toxicity and low patient compliance,limiting therapeutic efficacy and clinical benefit.Here,we report local dose-dense chemotherapy to treat TNBC by implanting 3D printed devices with timeprogrammed pulsatile release profiles.The implantable device can control the time between drug releases based on its internal microstructure design,which can be used to control dose density.The device is made of biodegradable materials for clinical convenience and designed for minimally invasive implantation via a trocar.Dose density variation of local chemotherapy using programmable release enhances anti-cancer effects in vitro and in vivo.Under the same dose density conditions,device-based chemotherapy shows a higher anticancer effect and less toxic response than intratumoral injection.We demonstrate local chemotherapy utilizing the implantable device that simulates the drug dose,number of releases,and treatment duration of the dose-dense AC(doxorubicin and cyclophosphamide)regimen preferred for TNBC treatment.Dose density modulation inhibits tumor growth,metastasis,and the expression of drug resistance-related proteins,including p-glycoprotein and breast cancer resistance protein.To the best of our knowledge,local dose-dense chemotherapy has not been reported,and our strategy can be expected to be utilized as a novel alternative to conventional therapies and improve anti-cancer efficiency.

Weight gain after 35 years of age is associated with increased breast cancer risk: findings from a large prospective cohort study

Adiposity affects lifetime estrogen exposure,which is a key factor in breast carcinogenesis.However,adiposity effects,often assessed as the body mass index(BMI),on pre-and post-menopausal breast cancer risk are paradoxical.Body weight gain may reflect body fat mass accumulation during adulthood better than the BMI,potentially representing age-related metabolic changes.

UBE2T mediates the stemness properties of breast cancer cells through the mTOR signaling pathway

Objectives:This study aimed to reveal the role and possible mechanism of the ubiquitin-conjugating enzyme 2T(UBE2T)in the biological activities of breast cancer stem cells(BCSCs).Methods:The specific protein and gene expression were quantified by Western blotting and quantitative real-time polymerase chain reaction,the proportion of BCSCs was examined by flow cytometry,and the self-renewal and proliferation of BCSCs were verified by serial sphere formation and soft agar.Results:Increasing expression of UBE2T was drastically found in breast cancer than that in adjacent tissues.Furthermore,UBE2T overexpression significantly increased the proportion of BCSCs in breast cancer cells and promoted their self-renewal and proliferation.Silent UBE2T exhibited the opposite functions.UBE2T increased the levels of the mammalian target of rapamycin and the phosphorylated mammalian target of rapamycin.Mammalian target of rapamycin(mTOR)inhibitor rapamycin inhibited the function of UBE2T in BCSCs.Conclusion:UBE2T plays a role in BCSCs through mTOR pathway and may suggest a novel therapeutic strategy for breast cancer.

Predicting the Prognosis and Immunotherapeutic Response of Triple-Negative Breast Cancer by Constructing a Prognostic Model Based on CD8+T Cell-Related Immune Genes

Objective Triple-negative breast cancer(TNBC)poses a significant challenge for treatment efficacy.CD8+T cells,which are pivotal immune cells,can be effectively analyzed for differential gene expression across diverse cell populations owing to rapid advancements in sequencing technology.By leveraging these genes,our objective was to develop a prognostic model that accurately predicts the prognosis of patients with TNBC and their responsiveness to immunotherapy.Methods Sample information and clinical data of TNBC were sourced from The Cancer Genome Atlas and METABRIC databases.In the initial stage,we identified 67 differentially expressed genes associated with immune response in CD8+T cells.Subsequently,we narrowed our focus to three key genes,namely CXCL13,GBP2,and GZMB,which were used to construct a prognostic model.The accuracy of the model was assessed using the validation set data and receiver operating characteristic(ROC)curves.Furthermore,we employed various methods,including Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway,immune infiltration,and correlation analyses with CD274(PD-L1)to explore the model's predictive efficacy in immunotherapeutic responses.Additionally,we investigated the potential underlying biological pathways that contribute to divergent treatment responses.Results We successfully developed a model capable of predicting the prognosis of patients with TNBC.The areas under the curve(AUC)values for the 1-,3-,and 5-year survival predictions were 0.618,0.652,and 0.826,respectively.Employing this risk model,we stratified the samples into high-and low-risk groups.Through KEGG enrichment analysis,we observed that the high-risk group predominantly exhibited enrichment in metabolism-related pathways such as drug and chlorophyll metabolism,whereas the low-risk group demonstrated significant enrichment in cytokine pathways.Furthermore,immune landscape analysis revealed noteworthy variations between(PD-L1)expression and risk scores,indicating that our model effectively predicted the response of patients to immune-based treatments.Conclusion Our study demonstrates the potential of CXCL13,GBP2,and GZMB as prognostic indicators of clinical outcomes and immunotherapy responses in patients with TNBC.These findings provide valuable insights and novel avenues for developing immunotherapeutic approaches targeting TNBC.

Chinese herbal medicine for the treatment of endocrine therapyrelated osteoporosis among patients with breast cancer:A systematic review and meta-analysis

Objective:To assess the efficacy and safety of combining traditional Chinese medicine(TCM),specifically Chinese herbal medicine(CHM),with Western medicine(WM),compared to WM alone to treat breast cancer endocrine therapy-related osteoporosis(BCET-OP)by meta-analysis.Methods:Thirty-eight randomized controlled trials involving 2170 participants were analyzed.Eight databases were searched for articles published between inception and December 2023.Quality assessment was performed using the Risk of Bias 2 tool.Results:Significant increases were observed in the TCM-WM group in lumbar vertebrae bone mineral density(BMD)(P<.001,mean difference(MD)=0.07,95%confidence interval(CI):0.06 to 0.08),lumbar vertebrae T-score(P=.0005,MD=0.21,95%CI:0.09 to 0.33)and collum femoris BMD(P=.01,MD=0.10,95%CI:0.02 to 0.19).No significant difference was observed between the groups in the collum femoris T-score and estradiol levels.Bone gla-protein levels were significantly increased in the TCM-WM group(P=.0002,MD=0.52,95%CI:0.25 to 0.79).Beta-CrossLaps decreased significantly in the TCM-WM group(P=.0008,MD=−0.10,95%CI:−0.16 to−0.04).No significant difference was observed between the TCM-WM and WM groups in alkaline phosphatase,in procollagen type I N-terminal propeptide,and in the Kupperman index.The visual analog score(VAS)was decreased in the TCM-WM group compared to the WM group(P<.001,MD=−1.40,95%CI:−1.94 to−0.87).No significant difference in adverse events was observed between the two groups.Conclusion:Combining CHM with WM in patients with BCET-OP significantly improved BMD,T-score,and certain bone turnover markers and reduced the VAS score,indicating potential benefits for bone health and related pain.Adverse event analysis revealed no differences between the groups,supporting the feasibility of the combination therapy.However,further research,particularly in diverse populations,is required.

Personalized Perioperative Care for a Patient with a 10-Year-Old Postpartum Old Thrombus after Neoadjuvant Therapy for Breast Cancer

Breast cancer is one of the most common malignant tumors in women, and has become the main cause threatening women’s health. A case of breast cancer with neoadjuvant chemotherapy was discharged after active treatment and nursing.

Anti-PD1 antibody and not anti-LAG-3 antibody improves the antitumor effect of photodynamic therapy for treating metastatic breast cancer

Photodynamic therapy(PDT)has limited effects in treating metastatic breast cancer.Immune checkpoints can deplete the function of immune cells;however,the expression of immune checkpoints after PDT is unclear.This study investigates whether the limited e±cacy of PDT is due to upregulated immune checkpoints and tries to combine the PDT and immune checkpoint inhibitor to observe the e±cacy.A metastatic breast cancer model was treated by PDT mediated by hematoporphyrin derivatives(HpD-PDT).The anti-tumor effect of HpD-PDT was observed,as well as CD4þT,CD8þT and calreticulin(CRT)by immunohistochemistry and immunofluorescence.Immune checkpoints on T cells were analyzed byflow cytometry after HpD-PDT.When combining PDT with immune checkpoint inhibitors,the antitumor effect and immune effect were assessed.For HpD-PDT at 100 mW/cm2 and 40,60 and 80 J/cm2,primary tumors were suppressed and CD4þT,CD8þT and CRT were elevated;however,distant tumors couldn't be inhibited and survival could not be prolonged.Immune checkpoints on T cells,especially PD1 and LAG-3 after HpD-PDT,were upregulated,which may explain the reason for the limited HpD-PDT effect.After PDT combined with anti-PD1 antibody,but not with anti-LAG-3 antibody,both the primary and distant tumors were signi-cantly inhibited and the survival time was prolonged,additionally,CD4þT,CD8þT,IFN-þCD4þT and TNF-þCD4þT cells were signi-cantly increased compared with HpD-PDT.HpD-PDT could not combat metastatic breast cancer.PD1 and LAG-3 were upregulated after HpD-PDT.Anti-PD1 antibody,but not anti-LAG-3 antibody,could augment the antitumor effect of HpD-PDT for treating metastatic breast cancer.

Network pharmacology and experimental validation to reveal the pharmacological mechanisms of Qizhu prescription for treating breast cancer

Objective:To investigate the mechanism underlying the effects exerted by the Qizhu prescription(QZP)in breast cancer(BC),and the respective targets.Methods: Expression data from the ArrayExpress and The Cancer Genome Atlas(TCGA)were used to identify differentially expressed genes(DEGs)in BC.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed on the DEGs to identify genes involved in protein–protein interactions.Molecular docking was used to explore the dynamic relationship between active molecules and targets.Cell function experiments and animal studies were conducted to evaluate the effects of hub genes and active QZP compounds on BC cell behavior.Results: Among the 25 evaluated BC-related targets of QZP,matrix metalloproteinase-1(MMP1)and epidermal growth factor receptor(EGFR)exhibited the highest degrees of dysregulation.GO and KEGG enrichment analyses revealed that the anti-BC targets of QZP primarily affected drug responses and pathways in cancer cells.Molecular docking analysis suggested potential interactions between EGFR and quercetin/luteolin,as well as between MMP1 and luteolin/kaempferol/quercetin.Quercetin significantly reduced BC cell proliferation,migration,invasion,and tumor development in vivo.Treatment of BC cells with quercetin decreased the expression or activation of several associated proteins.Conclusion: The findings of our study provide new insights into the therapeutic potential of traditional Chinese medicine against BC,with particular reference to QZP.

Dual ligand-targeted Pluronic P123 polymeric micelles enhance the therapeutic effect of breast cancer with bone metastases

Bone metastasis secondary to breast cancer negatively impacts patient quality of life and survival.The treatment of bone metastases is challenging since many anticancer drugs are not effectively delivered to the bone to exert a therapeutic effect.To improve the treatment efficacy,we developed Pluronic P123(P123)-based polymeric micelles dually decorated with alendronate(ALN)and cancer-specific phage protein DMPGTVLP(DP-8)for targeted drug delivery to breast cancer bone metastases.Doxorubicin(DOX)was selected as the anticancer drug and was encapsulated into the hydrophobic core of the micelles with a high drug loading capacity(3.44%).The DOX-loaded polymeric micelles were spherical,123 nm in diameter on average,and exhibited a narrow size distribution.The in vitro experiments demonstrated that a pH decrease from 7.4 to 5.0 markedly accelerated DOX release.The micelles were well internalized by cultured breast cancer cells and the cell death rate of micelle-treated breast cancer cells was increased compared to that of free DOX-treated cells.Rapid binding of the micelles to hydroxyapatite(HA)microparticles indicated their high affinity for bone.P123-ALN/DP-8@DOX inhibited tumor growth and reduced bone resorption in a 3D cancer bone metastasis model.In vivo experiments using a breast cancer bone metastasis nude model demonstrated increased accumulation of the micelles in the tumor region and considerable antitumor activity with no organ-specific histological damage and minimal systemic toxicity.In conclusion,our study provided strong evidence that these pH-sensitive dual ligand-targeted polymeric micelles may be a successful treatment strategy for breast cancer bone metastasis.

Exploring the molecular mechanism of Epimedium brevicornu Maxim.in treating breast cancer via network pharmacology and in vitro experiments

Objective:To evaluate the therapeutic effects of Epimedium brevicornu Maxim.(EBM,Yin Yang Huo)on breast cancer using network pharmacology and in vitro validation.It also aimed to explore the novel targets and mechanisms of EBM in the treatment of breast cancer to facilitate the discovery of new drugs and their clinical application.Methods: Network pharmacology was used to identify and screen the components and targets of EBM for breast cancer treatment.Molecular docking was further screened the effective components and targets of EBM.Wound-healing assays and flow cytometry analysis were used to detect the ability of two compounds to intervene in the migration and apoptosis of MDA-MB-231 cells,and their mechanism of action was further explored using western blotting experiments.Results: EBM contained 19 active components.Among them wereβ-anhydroicaritin(Anhy)and isoliquiritigenin(Iso),which were selected for in vitro experiments.Treatment resulted in a dose-dependent suppression of MDA-MB-231 cell viability,with an IC_(50) of 23.73μmol/L for Iso and 21.28μmol/L for Anhy.In the wound healing assay,cells in Anhy and Iso groups exhibited considerable inhibition of migration at 48 h.In flow cytometry analysis,treatment with Iso(20μmol/L)for 96 h resulted in significantly higher levels of both early and late apoptosis in the Iso group than that in the control group(P=.004 and P=.014,respectively).Additionally,both Iso(20μmol/L)and Anhy(10 and 20μmol/L)induced cell necrosis at 96 h.Western blotting revealed that Anhy and Iso increased the expression of Bax and TBK1/NAK.Conclusion: These findings suggested that Anhy and Iso,the two components of EBM,inhibit MDA-MB-231 cell proliferation and migration of and induce their apoptosis,providing substantial support for future studies on breast cancer.

Knowledge Practical Attitude of Health Professionals on Breast Cancer at the Hospital of the District of the Commune IV of Bamako

Introduction: The level of knowledge and attitude of health professionals about breast cancer are important determinants. General objective: To study the knowledge, attitude and practice of health professionals of the hospital of the district of the commune IV on breast cancer. Methodology: This was a cross-sectional, prospective, descriptive, qualitative and quantitative study. The study period was from 01 October 2022 to December 2022. Results: In one week of survey, 110 health workers (intern, obstetrician nurse, general practitioners and specialists) received the survey sheet, 80 health workers informed it, a participation rate of 73%. The male sex was most represented at 63.75% with a sex ratio of 1.76. The average age was 39.59 years with extremes of 22 and 61 years. The clinical signs evoked by the participants were: breast nodule (81.25%), followed by breast discharge (48.75%). In relation to risk factors: interns and obstetrician nurses had no good knowledge, 51.72% of general practitioners had good knowledge, 43.48% of specialist doctors had good knowledge, and 5.88% of the wise had good knowledge. Conclusion: Breast cancer is a common pathology around the world, health professionals are at the forefront of the fight against breast cancer, and this fight cannot be effective without trained personnel.

Clinical benefit and safety profile of cross-line therapy with CDK4/6 inhibitors:a retrospective study of HR+/HER2–advanced breast cancer

Objective:CDK4/6 inhibitors(CDK4/6is)in combination with endocrine therapy have secured a central role in the treatment of hormone receptor(HR)-positive advanced breast cancer(ABC)and have transformed the therapeutic landscape.Cross-line CDK4/6i therapy in which another CDK4/6i is continued after progression on a prior CDK4/6i may still offer advantageous therapeutic effects.Cross-line CDK4/6i therapy is an area of active investigation in the ongoing pursuit to improve outcomes for patients with HR+/human epidermal growth factor receptor 2(HER2)–ABC.Methods:This retrospective study enrolled 82 patients with HR+/HER2–ABC who were treated with cross-line CDK4/6is(abemaciclib,palbociclib,ribociclib,and dalpiciclib)after progression with another CDK4/6i.The primary endpoint was progression-free survival(PFS)according to version 1.1 of the Response Evaluation Criteria in Solid Tumors.Secondary endpoints included toxicity,objective response rate,disease control rate,and overall survival.Adverse events(AEs)were graded according to version 5.0 of the Common Terminology Criteria for Adverse Events,as promulgated by the U.S.Department of Health and Human Services.Results:Eighty-two HR+/HER2–ABC patients who received cross-line CDK4/6i therapy from January 2022 to February 2024 were enrolled.The median age of the patients was 60 years.The median PFS of all patients was 7.6 months(95%CI,5.9-9.2).Cox regression analysis identified lung metastasis and a switch to endocrine therapy following prior CDK4/6i therapy as independent predictive factors for PFS.Notably,patients who previously received abemaciclib and switched to palbociclib upon disease progression had a median PFS of 10.7 months.The strategy of transitioning to chemotherapy after progression on a prior CDK4/6i,then to a subsequent CDK4/6i merits further investigation.Hematologic toxicity was the most common grade≥3 AEs.No instances of fatal safety events were observed.Conclusions:Cross-line CDK4/6i therapy is associated with significant clinical benefits and manageable safety profiles in patients with HR+/HER2–ABC,which underscores cross-line CDK4/6i therapy potential as an effective treatment strategy.

Women Breast Cancer: Knowledge, Attitudes, Practices and Factors Associated with Early Screening in the Municipality of Abomey-Calavi in Benin in 2018

Background: Breast cancer is the dominant cancer in women in both developed and developing countries. The objective of this study was to assess the knowledge, attitudes, practices and factors associated with early breast cancer screening among women in the Municipality of Abomey-Calavi in Benin. Methods: This was a cross-sectional, descriptive, analytical study with prospective data collection from October 1 to 8, 2018, involving 1740 women in the Municipality of Abomey-Calavi, aged 18 years or older and selected by WHO four-stage random cluster sampling. Consenting women who were mentally competent, 18 years of age or older at the time of the survey, and residing continuously in the Municipality of Abomey-Calavi for the last six months prior to the survey were included. On the other hand, women who belonged to a breast cancer prevention service, women in whom secondary screening was noted, or non-consenting women were not included. The initial minimum size was estimated by the Schwartz formula with a cluster effect of k = 2. Information was collected by questionnaire survey, entered with Epidata 3.1. Fr and analyzed with R Studio 3.5.1. software. Results: The mean age of the women surveyed was 32.0 ± 11.5 years with a range of 18 and 71 years. Regarding knowledge, the clinical manifestation known by the majority of women was the presence of a nodule (68.50%). In the series, 1308 (75.17%) declared having heard about breast cancer once before, either on the radio, television or from friends and 726 (55.50%) had heard about breast cancer screening. Five hundred and twelve (70.52%) of the 726 who had heard of breast cancer said they knew that breast cancer could be screened earlier. Breast self-examination was the most cited screening method (67.58%). The disease is of natural origin according to 37.84% of them. Regarding attitudes and practices, the prevalence of early breast cancer screening was 12.93%, of which 11.67% declared that they had checked themselves to know whether they were carriers of the disease or not. The main means of the early screening used was breast self-examination (85.78%). Factors associated with early breast cancer screening found in multivariate analysis were age (≤50 years), education level (increasingly higher), marital status (married/coupled), place of residence (downtown), and socioeconomic level (average/high). Conclusion: The frequency of early breast cancer screening among women is still low in the municipality of Abomey-Calavi, although they have a good knowledge of the disease. This raises the need to strengthen awareness of early breast cancer screening.

Molecular mechanisms of ferroptosis and its role in the treatment of breast cancer

Breast cancer is a critical threat to women around the globe. Current radio- and chemotherapy regimens can induce multiple drug-resistant effects, e.g., anti-apoptosis, anti-pyroptosis, and anti-necroptosis, causing a poor clinical response to therapy. Ferroptosis is a newly programmed cell death characterized by iron overload, the massive production of reactive oxygen species (ROS), and membrane lipid peroxidation. The occurrence of ferroptosis results from an imbalance between peroxidation mechanisms (execution systems) and anti- oxidation mechanisms (defense systems), including the iron metabolism pathway, amino acid metabolism pathway, and lipid metabolism pathway. Recently, the vital role of ferroptosis in various diseases, including cancer, hypertension, diabetes, and Alzheimer's, has been identified. Specifically, triggering ferroptosis in breast cancer cells can inhibit their proliferation and invasion, and improve the chemoradiotherapy sensitivity, which makes it a potential strategy for breast cancer therapy. This review summarizes the definition and features of ferroptosis, as well as its role in the treatment of breast cancer, aimed at providing a theoretical basis for future drug development.

Effects of psychological intervention on negative emotions and psychological resilience in breast cancer patients after radical mastectomy

Breast cancer(BC)is the most common malignant tumor in women,and the treatment process not only results in physical pain but also significant psychological distress in patients.Psychological intervention(PI)has been recognized as an important approach in treating postoperative psychological disorders in BC patients.It has been proven that PI has a significant therapeutic effect on postoperative psychological disorders,improving patients'negative emotions,enhancing their psychological resilience,and effectively enhancing their quality of life and treatment compliance.

Immunohistochemical Profile of Breast Cancer: A Retrospective Study in the Democratic Republic of Congo

Background: The management of breast cancer increasingly requires molecular classification based on immunohistochemistry. As breast cancer is a heterogeneous disease characterized by the accumulation of multiple molecular alterations that give each tumour its own phenotype and evolutionary potential, immunohistochemistry, as a complementary technique to morphological examination, determines the status of hormone receptors and on protein in tumour cells, which are predictive and prognostic markers of breast cancer. This technique is often little used in the Democratic Republic of Congo (DRC), as this study shows. The under-use of this technique due to a lack of equipment and/or human skills explains the paucity of epidemiological data available to date. Objective: Determine the immunohistochemical profile of breast cancer. Methodology: This is a retrospective study carried out in the Anapath Department of the NGANDA Hospital from January 1, 2020 to December 31, 2022, i.e. a 3-year period. Result: A total of 736 patients were registered in the hospitalization register of the Oncology Department of CH NGANDA for the period corresponding to the present study. Breast cancer was diagnosed in 110 patients, representing 14.9% of all cases. The mean age of the patients was 58.4 ± 8.2 years, with extremes ranging from 30 to 76 years. Breast nodules were the most common reason for diagnosis in 56.3% of cases, with Luminal A dominating in 17.3%. Conclusion: Breast cancer is a major public health problem. Worldwide, it is the most frequently diagnosed cancer in women and the leading cause of cancer-related death in women. In the Democratic Republic of Congo, because of the delay in consulting our patients and the weakness of systematic screening, patients are seen at an advanced stage of the disease. Treatment is multidisciplinary, involving surgery, radiotherapy, chemotherapy (including targeted therapies) and hormone therapy. Patient awareness and screening campaigns will contribute to a considerable reduction in the delay in diagnosis and the morbidity and mortality associated with breast cancer.

Downregulation of the circadian clock gene period 2 aggravates prognosis in breast cancer patients with obesity

Background:Obese individuals diagnosed with breast cancer often experience a less favorable prognosis;however,the underlying mechanisms linking obesity to breast cancer outcomes remain elusive.This study aimed to identify and validate novel prognostic markers associated with breast cancer in patients with obesity.Methods:We conducted a reanalysis of gene expression profiles from normal-weight,overweight,and obese breast cancer patients to identify candidate genes.Subsequently,we validated the protein levels of these candidates using immunohistochemistry.Finally,we investigated the association between candidate genes and breast cancer prognosis at Tongji Hospital,utilizing data from an 8-year follow-up through the Kaplan-Meier method and univariate and multivariate Cox regression models.Results:The fold change of the circadian clock gene period 2(PER2),which exhibited a declining trend with increasing body mass index,was 0.76 in obese patients compared with normal-weight patients.The expression rates of PER2 protein were 44.7%,51.5%,and 61.3%in normal-weight,overweight,and obese patients,respectively.The 8-year recurrence-free survival rates were 75.9%,69.6%,and 64.1%,whereas the 8-year overall survival rates were 86.8%,83.0%,and 76.1%in normal-weight,overweight,and obese patients,respectively(P<0.05).Furthermore,the 8-year recurrence-free survival rates were 66.2%and 76.4%,and the 8-year overall survival rates were 79.9%and 86.3%in the low and high PER2 expression groups,respectively(P<0.05).The unadjusted hazard ratio for PER2 was 1.550(95%confidence interval,1.029–2.335),and the adjusted hazard ratio was 3.003(95%confidence interval,1.838–4.907).Conclusions:Our findings indicate that low PER2 expression serves as an independent risk factor for breast cancer prognosis and may contribute to the unfavorable outcomes observed in obese patients.

DDHD2 is involved in the malignant progression of early luminal A breast cancer by changing cell membrane proteins and immune responses functionality

Background:Luminal A breast cancer has the best prognosis of all malignant breast cancer types.In clinical practice,some patients with luminal A breast cancer present with small tumors(usually<20 mm)but with lymph node metastases or even distant organ metastasis.Owing to their insensitivity to chemotherapy and the lack of conclusive clinical evidence,there is a significant gap in research on luminal A breast cancer with high invasiveness.This study aimed to identify genes that drive the invasiveness of luminal A breast cancer and explore the underlying mechanisms.Methods:In this study,we first utilized bioinformatics techniques to analyze differentially expressed mRNAs and enrich common functional pathways to identify the target gene DDHD domain containing 2(DDHD2).We then evaluated the association between DDHD2 expression and patient prognosis,genetic material changes,and transcriptional,translational,and immune responses in luminal A breast cancer.We also conducted experiments at the molecular and cellular levels to validate these biochemical mechanisms.Results:The expression of DDHD2 varied between patients with low-grade luminal A breast cancer with and without lymph node metastases.Our findings demonstrated that DDHD2 exerted carcinogenic effects through various pathways by altering cell adhesion and migration,regulating cell proliferation and apoptosis cycles,and suppressing immune responses.Moreover,a pathway through which DDHD2 inhibited immunity was preliminarily verified.Conclusions:The results revealed a novel role for DDHD2 in promoting the malignant transformation and invasiveness of luminal A breast cancer.Considering its effects on the tumor microenvironment and tumor-infiltrating immune cells in the epithelial-mesenchymal transition,DDHD2 is proposed as a reliable direction for future immunotherapy and a potential target in luminal A breast cancer immune resistance.

Elucidating the molecular basis of ATP-induced cell death in breast cancer: Construction of a robust prognostic model

BACKGROUND Breast cancer is a multifaceted and formidable disease with profound public health implications.Cell demise mechanisms play a pivotal role in breast cancer pathogenesis,with ATP-triggered cell death attracting mounting interest for its unique specificity and potential therapeutic pertinence.AIM To investigate the impact of ATP-induced cell death(AICD)on breast cancer,enhancing our understanding of its mechanism.METHODS The foundational genes orchestrating AICD mechanisms were extracted from the literature,underpinning the establishment of a prognostic model.Simultaneously,a microRNA(miRNA)prognostic model was constructed that mirrored the gene-based prognostic model.Distinctions between high-and low-risk cohorts within mRNA and miRNA characteristic models were scrutinized,with the aim of delineating common influence mechanisms,substantiated through enrichment analysis and immune infiltration assessment.RESULTS The mRNA prognostic model in this study encompassed four specific mRNAs:P2X purinoceptor 4,pannexin 1,caspase 7,and cyclin 2.The miRNA prognostic model integrated four pivotal miRNAs:hsa-miR-615-3p,hsa-miR-519b-3p,hsa-miR-342-3p,and hsa-miR-324-3p.B cells,CD4+T cells,CD8+T cells,endothelial cells,and macrophages exhibited inverse correlations with risk scores across all breast cancer subtypes.Furthermore,Kyoto Encyclopedia of Genes and Genomes analysis revealed that genes differentially expressed in response to mRNA risk scores significantly enriched 25 signaling pathways,while miRNA risk scores significantly enriched 29 signaling pathways,with 16 pathways being jointly enriched.CONCLUSION Of paramount significance,distinct mRNA and miRNA signature models were devised tailored to AICD,both potentially autonomous prognostic factors.This study's elucidation of the molecular underpinnings of AICD in breast cancer enhances the arsenal of potential therapeutic tools,offering an unparalleled window for innovative interventions.Essentially,this paper reveals the hitherto enigmatic link between AICD and breast cancer,potentially leading to revolutionary progress in personalized oncology.