Distant metastasis remains the primary cause of morbidity in patients with breast cancer. Hence, the development of more efficacious strategies and the exploration of potential targets for patients with metastatic breast cancer are urgently needed. The data of six patients with breast cancer brain metastases (BCBrM) from two centres were collected, and a comprehensive landscape of the entire tumour ecosystem was generated through the utilisation of single‐cell RNA sequencing. We utilised the Monocle2 and CellChat algorithms to investigate the interrelationships among each subcluster. In addition, multiple signatures were collected to evaluate key components of the subclusters through multi‐omics methodologies. Finally, we elucidated common expression programs of malignant cells, and experiments were conducted in vitro and in vivo to determine the functions of interleukin enhancer‐binding factor 2 (ILF2), which is a key gene in the metastasis module, in BCBrM progression. We found that subclusters in each major cell type exhibited diverse characteristics. Besides, our study indicated that ILF2 was specifically associated with BCBrM, and experimental validations further demonstrated that ILF2 deficiency hindered BCBrM progression. Our study offers novel perspectives on the heterogeneity of BCBrM and suggests that ILF2 could serve as a promising biomarker or therapeutic target for BCBrM.

The chemokine (C-X-C motif) ligand (CXCL) family in tumor tissue is closely related to tumor growth, metastasis, and survival. However, the differential expression profile and prognostic value of the CXCLs in ovarian cancer (OC) have not been elucidated. Therefore, we studied the expression levels and mutations of CXCLs in OC patient in TCGA and various public databases. The expression differences of CXCLs in OC cancer tissues and normal tissues were compared through the Gene Expression Profiling Interactive Analysis (GEPIA) database. The effect of CXCLs on OC prognosis was analyzed using the Kaplan-Meier curves in GEPIA database. The impact of CXCLs on immune infiltration and clinicopathological outcomes in OC was assessed using the TIMER algorithm. Compared with normal tissues, we found that eight CXCLs were significantly differentially expressed in OC. The expression levels of CXCL9 ( ), CXCL11 ( ), and CXCL13 ( ) were significantly associated with tumor stage. CXCL13 was the only gene that significantly affected both disease-free survival (DFS) and overall survival (OS) in OC, and higher CXCL13 transcript levels implied longer DFS and OS. Although there was no significant impact on DFS, CXCL10 ( ) and CXCL11 ( ) expression levels had a significant effect on OS in OC. At the same time, CXCLs were significantly associated with several immune-infiltrating cells in OC tissues. The CXCLs were significantly associated with one or more immune-infiltrating cells in OC tissue. CXCL13 was differentially expressed in OC and significantly affected the prognosis of patients and was a potential marker of OC prognosis.

Phosphoglycerate mutase 1 (PGAM1) has been identified as a key player in the progression and metastasis of various human cancer types, including breast cancer (BC); however, its precise oncogenic mechanism remains unclear. The present study aimed to investigate the oncogenic mechanisms of PGAM1 and establish its potential as a therapeutic target. Comprehensive analyses from the Tumor Immune Estimation Resource 2.0 and The Cancer Genome Atlas databases revealed a significant upregulation of PGAM1 in BC, correlating with poor clinical outcomes. Additionally, elevated expression of PGAM1 was confirmed in clinical BC samples. Silencing PGAM1 with specific small hairpin RNA in BC cells resulted in a marked reduction in cell proliferation, invasiveness and migration, alongside increased apoptosis and cell cycle arrest. In vivo experiments using tumor-bearing nude mice demonstrated that PGAM1 knockdown significantly reduced tumor volume and weight, effectively inhibiting tumor growth. Mechanistic investigations suggested that PGAM1 promoted BC tumorigenesis through the activation of the Wnt/β-catenin signaling pathway, both in vitro and in vivo. Therefore, the upregulation of PGAM1 in BC enhances malignancy via the Wnt/β-catenin signaling pathway, highlighting PGAM1 as a promising therapeutic target for BC treatment.

The metabolic enzyme phosphoglycerate mutase enzyme 1 (PGAM1) is a key enzyme in the glycolysis pathway, and glycolysis is closely related to cancer progression, suggesting that PGAM1 may have important functions in breast cancer. We used sequencing data from the Oncomine database and UALCAN database to analyze the expression of PGAM1 and its influence on the clinicopathological characteristics of breast cancer. LinkedOmics was used to identify genes related to PGAM1 expression, kinases, miRNAs, and transcription factors that were significantly related to PGAM1 through GSEA. cBioPortal was used to identify the alternation frequency and form of PGAM1 in breast cancer. The expression level of PGAM1 in breast cancer was significantly higher than that in normal tissues. Moreover, the expression level of PGAM1 is closely related to the molecular subtype and TP53 mutation status. The expression level of PGAM1 in HER2‐positive and triple‐negative tumors was significantly higher than that of luminal type. The expression level of PGAM1 in TP53‐mutant tumors was higher than that in non‐TP53‐mutant tumors. In addition, the overall survival of patients with high PGAM1 expression was significantly worse than that of patients with low expression (P = 0.0077). Through GSEA analysis, we found multiple kinases, miRNAs, and transcription factors significantly related to PFKFB4. cBioPortal analysis showed that the mutation rate of PGAM1 in breast cancer was relatively low (4%), and the main form of mutation was high mRNA expression. This study suggests that PGAM1 is a potential diagnostic and prognostic marker in breast cancer. Through data mining, we revealed the potential regulatory network information of PGAM1, laying a foundation for further research on the role of PGAM1 in breast cancer.

Background: Male breast cancer (MBC) is rare, which has restricted prospective research among MBC patients. With effective treatments, the prognosis of MBC patients has improved and developing a second primary malignancy (SPM) has become a life-threatening event for MBC survivors. However, few studies have focused on the prognosis of MBC patients and looked into the SPM issue in MBC survivors.Method: We reviewed MBC patients diagnosed between 1990 and 2016 from the latest Surveillance, Epidemiology, and End Results (SEER) Plus database. Competing risk models and nomograms were conducted for predicting the risk of cancer-specific death and SPM occurrence. C-indexes, calibration curves, ROC curves, and decision curve analysis (DCA) curves were applied for validation.Result: A total of 1,843 MBC patients with complete information were finally enrolled and 60 (3.26%) had developed an SPM. Prostate cancer (40%) was the most common SPM. The median OS of all the enrolled patients was 102.41 months, while the median latency from the initial MBC diagnosis to the subsequent diagnosis of SPM was 67.2 months. The patients who suffered from an SPM shared a longer OS than those patients with only one MBC (p = 0.027). The patients were randomly divided into the development cohort and the validation cohort (at a ratio of 7:3). The Fine and Gray competing risk model was used to identify the risk factors. Two nomograms were constructed and validated to predict the 5-year, 8-year, and 10-year survival probability of MBC patients, both of which had good performance in the C-index, ROC curves, calibration plots, and DCA curves, showing the ideal discrimination capability and predictive value clinically. Furthermore, we, for the first time, constructed a nomogram based on the competing risk model to predict the 5-year, 8-year, and 10-year probability of developing an SPM in MBC survivors, which also showed good discrimination, calibration, and clinical effectiveness.Conclusion: We, for the first time, included treatment information and clinical parameters to construct a nomogram to predict not only the survival probability of MBC patients but also the probability of developing an SPM in MBC survivors, which were helpful in individual risk estimation, patient follow-up, and counseling in MBC patients.

Rationale: Breast low-grade adenosquamous carcinoma is an uncommon cancer that has been neglected in genetic and pathophysiological research. Consequently, medical practitioners face challenges in the effective diagnosis and treatment of this condition. Patient concerns: We present the case of a 57-year-old Asian female patient who presented with bilateral breast masses on physical examination. Ultrasound and an MRI revealed a highly suspicious malignant mass in her right breast that was completely removed surgically. Diagnoses: After pathological analysis, the diagnosis was low-grade adenosquamous carcinoma with local high-grade transformation, and some of the tumor components were estrogen receptor positive. Interventions: The patient underwent appropriate postoperative chemotherapy and achieved a favorable outcome. Outcomes: During the follow-up period after surgical resection, the patient did not experience any local recurrence or distant metastasis. Lessons: Owing to the rare combination of estrogen receptor positivity and high-grade progression, this patient also required adjuvant chemotherapy. This enhances the essential foundation for diagnosing and treating this rare disease, and facilitates the implementation of treatment plans.