Fungal Plasma Membrane H+-ATPase: Structure, Mechanism, and Drug Discovery.

The fungal plasma membrane H+-ATPase (Pma1) pumps protons out of the cell to maintain the transmembrane electrochemical gradient and membrane potential. As an essential P-type ATPase uniquely found in fungi and plants, Pma1 is an attractive antifungal drug target. Two recent Cryo-EM studies on Pma1 have revealed its hexameric architecture, autoinhibitory and activation mechanisms, and proton transport mechanism. These structures provide new perspectives for the development of antifungal drugs targeting Pma1. In this article, we review the history of Pma1 structure determination, the latest structural insights into Pma1, and drug discoveries targeting Pma1.

Structure of a fungal 1,3-ß-glucan synthase.

1,3-ß-Glucan serves as the primary component of the fungal cell wall and is produced by 1,3-ß-glucan synthase located in the plasma membrane. This synthase is a molecular target for antifungal drugs such as echinocandins and the triterpenoid ibrexafungerp. In this study, we present the cryo-electron microscopy structure of Saccharomyces cerevisiae 1,3-ß-glucan synthase (Fks1) at 2.47-Å resolution. The structure reveals a central catalytic region adopting a cellulose synthase fold with a cytosolic conserved GT-A-type glycosyltransferase domain and a closed transmembrane channel responsible for glucan transportation. Two extracellular disulfide bonds are found to be crucial for Fks1 enzymatic activity. Through structural comparative analysis with cellulose synthases and structure-guided mutagenesis studies, we gain previously unknown insights into the molecular mechanisms of fungal 1,3-ß-glucan synthase.

Gut microbiota and transcriptome dynamics in every-other-day fasting are associated with neuroprotection in rats with spinal cord injury.

Introduction: Every-other-day fasting (EODF) is a classical intermittent fasting (IF) mode with neuroprotective effects that promotes motor function recovery after spinal cord injury (SCI) in rats. However, its dynamic effects on the gut microbiota and spinal cord transcriptome remain unknown. Methods: In this study, 16S rRNA sequencing and RNA-seq analysis were used to investigate the effects of ad libitum (AL) and EODF dietary modes on the structural characteristics of rat gut microbiota in rats and the spinal cord transcriptome at various time points after SCI induction. Results: Our results showed that both dietary modes affected the bacterial community composition in SCI rats, with EODF treatment inducing and suppressing dynamic changes in the abundances of potentially anti-inflammatory and pro-inflammatory bacteria. Furthermore, the differentially expressed genes (DEGs) enriched after EODF intervention in SCI rats were associated with various biological events, including immune inflammatory response, cell differentiation, protein modification, neural growth, and apoptosis. In particular, significant spatiotemporal differences were apparent in the DEGs associated with neuroprotection between the EODF and AL interventions. These DGEs were mainly focused on days 1, 3, and 7 after SCI. The relative abundance of certain genera was significantly correlated with DEGs associated with neuroprotective effects in the EODF-SCI group. Discussion: Our results showed that EODF treatment may exert neuroprotective effects by modulating the transcriptome expression profile following SCI in rats. Furthermore, gut microbiota may be partially involved in mediating these effects.

RNA atlas and competing endogenous RNA regulation in tissue-derived exosomes from luminal B and triple-negative breast cancer patients.

Background: Luminal B and triple-negative breast cancer (TNBC) are malignant subtypes of breast cancer (BC), which can be attributed to the multifaceted roles of tissue-derived exosomes (T-exos). Competing endogenous RNA (ceRNA) networks can regulate gene expression post-transcriptionally. Methods: RNAs in T-exos from luminal B BC (n=8) and TNBC (n=8) patients were compared with those from persons with benign breast disease (n=8). The differentially expressed (DE) mRNA, microRNA (miRNA), and long noncoding RNA (lncRNA) target genes were annotated using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) to reveal the relevant biological processes.The ceRNA networks were constructed to show distinct regulation, and the mRNAs involved were annotated. The miRNAs involved in the ceRNA networks were screened with the Kaplan-Meier Plotter database to identify dysregulated ceRNAs with prognostic power. Results: In total, 802 DE mRNAs, 441 DE lncRNAs, and 104 DE miRNAs were identified in luminal B BC T-exos, while 1699 DE mRNAs, 590 DE lncRNAs, and 277 DE miRNAs were identified in TNBC T-exos. Gene annotation revealed that the RAS-MAPK pathway was the primary biological process in luminal B BC T-exos, while endocrine system development and growth were the main processes in TNBC T-exos. Survival analysis established seven survival-related lncRNA/miRNA/mRNA regulations in luminal B BC T-exos, and nineteen survival-related lncRNA/miRNA/mRNA regulations in TNBC T-exos. Conclusion: In addition to survival-related ceRNA regulations, ceRNA regulation of RAS-MAPK in luminal B and endocrine system development and growth regulation in TNBC might contribute to the tumorigenesis of BC.

Circulating cell-free DNA-based methylation patterns for breast cancer diagnosis.

Mammography is used to detect breast cancer (BC), but its sensitivity is limited, especially for dense breasts. Circulating cell-free DNA (cfDNA) methylation tests is expected to compensate for the deficiency of mammography. We derived a specific panel of markers based on computational analysis of the DNA methylation profiles from The Cancer Genome Atlas (TCGA). Through training (n = 160) and validation set (n = 69), we developed a diagnostic prediction model with 26 markers, which yielded a sensitivity of 89.37% and a specificity of 100% for differentiating malignant disease from normal lesions [AUROC = 0.9816 (95% CI: 96.09-100%), and AUPRC = 0.9704 (95% CI: 94.54-99.46%)]. A simplified 4-marker model including cg23035715, cg16304215, cg20072171, and cg21501525 had a similar diagnostic power [AUROC = 0.9796 (95% CI: 95.56-100%), and AUPRC = 0.9220 (95% CI: 91.02-94.37%)]. We found that a single cfDNA methylation marker, cg23035715, has a high diagnostic power [AUROC = 0.9395 (95% CI: 89.72-99.27%), and AUPRC = 0.9111 (95% CI: 88.45-93.76%)], with a sensitivity of 84.90% and a specificity of 93.88%. In an independent testing dataset (n = 104), the obtained diagnostic prediction model discriminated BC patients from normal controls with high accuracy [AUROC = 0.9449 (95% CI: 90.07-98.91%), and AUPRC = 0.8640 (95% CI: 82.82-89.98%)]. We compared the diagnostic power of cfDNA methylation and mammography. Our model yielded a sensitivity of 94.79% (95% CI: 78.72-97.87%) and a specificity of 98.70% (95% CI: 86.36-100%) for differentiating malignant disease from normal lesions [AUROC = 0.9815 (95% CI: 96.75-99.55%), and AUPRC = 0.9800 (95% CI: 96.6-99.4%)], with better diagnostic power and had better diagnostic power than that of using mammography [AUROC = 0.9315 (95% CI: 89.95-96.34%), and AUPRC = 0.9490 (95% CI: 91.7-98.1%)]. In addition, hypermethylation profiling provided insights into lymph node metastasis stratifications (p < 0.05). In conclusion, we developed and tested a cfDNA methylation model for BC diagnosis with better performance than mammography.

Silencing of PGK1 Promotes Sensitivity to Paclitaxel Treatment by Upregulating XAF1-Mediated Apoptosis in Triple-Negative Breast Cancer.

Objective: Triple negative breast cancer (TNBC) is known to have aggressive clinical course and a high risk of recurrence. Given the lack of effective targeted therapy options, paclitaxel-based chemotherapy is still the primary option for TNBC patients. However, patients who fail to achieve a complete response during neoadjuvant chemotherapy may be mainly due to sensitivity and resistance to chemotherapy. Thus, we concentrated the present research on the role of PGK1 in the sensitivity to paclitaxel treatment and the possible underlying mechanisms in TNBC. Methods: After exposure to paclitaxel, a cell viability analysis was made to investigate the influence of PGK1 silencing on cell death. The effect of PGK1 on apoptosis induced by paclitaxel treatment was examined in vitro by flow cytometry cell apoptosis assays. Western blotting was performed to examine the impact of PGK1 on paclitaxel-induced apoptosis. The correlation of PGK1 with apoptosis-associated protein X-linked inhibitor of apoptosis (XIAP)-associated factor 1 (XAF1) was analyzed in 39 specimens by immunohistochemistry analysis. Results: We observed that silencing PGK1 sensitized triple-negative breast cancer (TNBC) cell lines to paclitaxel treatment as a result of increased drug-induced apoptosis. Furthermore, mechanistic investigations suggested that XAF1 was increased in PGK1-knockdown cells along with the expression of the apoptotic proteins including cleaved caspase-3 and Bax. Immunohistochemistry analysis showed that PGK1 was negatively related to XAF1. Moreover, we found that downregulation of XAF1 reduced paclitaxel-induced apoptosis in PGK1-silenced triple-negative cell lines. Conclusion: Our results identified PGK1 as a potential biomarker for the treatment of TNBC, and inhibition of PGK1 expression might represent a novel strategy to sensitize TNBC to paclitaxel treatment.

Expression and prognostic values of ARID family members in breast cancer.

The ARID family is a superfamily of 15 members containing a domain that interacts with AT-rich DNA elements. However, the expression and prognostic roles of each ARID in breast cancer are still elusive. We used the TCGA and Kaplan-Meier plotter databases to assess the expression and prognostic values of ARID mRNA levels in breast cancer respectively. In the present study, 6 members were significantly lower in tumor tissues than those in the normal tissues, while 6 members were significantly higher. Further assessment of ARID expression in breast cancer with different molecular subtypes, 3 members were significantly higher in no-luminal molecular subtype than those in the luminal molecular subtype, and 6 members were significantly higher. In regard to prognostic values, high expression of ARID1A, ARID2, ARID3B, ARID4A, ARID5A, ARID5B, JARID1A were associated with favorable outcome, while ARID4B and JARID1B were correlated to a worse outcome. We further analyzed the prognostic value of ARID in different intrinsic subtypes and clinicopathological features of breast cancer. We found many meaningful ARID family biomarkers in breast cancer. The relevant results will expound the role of ARID in breast cancer and may further provide new insight to explore the ARID-targeting reagents for treating breast cancer patients.

LncRNA TINCR favors tumorigenesis via STAT3-TINCR-EGFR-feedback loop by recruiting DNMT1 and acting as a competing endogenous RNA in human breast cancer.

The long noncoding RNA (lncRNA) TINCR has recently been found to be associated with the progression of human malignancies, but the molecular mechanism of TINCR action remains elusive, particularly in breast cancer. The oncogenic role of TINCR was examined in vitro and in vivo in breast cancer. Next, the interaction between TINCR, DNMT1, and miR-503-5p methylation was explored. Moreover, the mechanism by which TINCR enhances EGFR expression and downstream signaling via an RNA-RNA interaction was comprehensively investigated. Furthermore, upstream transcriptional regulation of TINCR expression by STAT3 was examined by performing chromatin immunoprecipitation. Finally, feedback signaling in the STAT3-TINCR-EGFR downstream cascade was also investigated. TINCR is upregulated in human breast cancer tissues, and TINCR knockdown suppresses tumorigenesis in vitro and in vivo. Mechanistically, TINCR recruits DNMT1 to the miR-503-5p locus promoter, which increases the methylation and suppresses the transcriptional expression of miR-503-5p. Furthermore, TINCR also functions as a competing endogenous RNA to upregulate EGFR expression by sponging miR-503-5p. In addition, TINCR stimulates JAK2-STAT3 signaling downstream from EGFR, and STAT3 reciprocally enhances the transcriptional expression of TINCR. Our findings broaden the current understanding of the diverse manners in which TINCR functions in cancer biology. The newly identified STAT3-TINCR-EGFR-feedback loop could serve as a potential therapeutic target for human cancer.

Preliminary Application of a Quantitative Collateral Assessment Method in Acute Ischemic Stroke Patients With Endovascular Treatments: A Single-Center Study.

Objectives: To develop an efficient and quantitative assessment of collateral circulation on time maximum intensity projection CT angiography (tMIP CTA) in patients with acute ischemic stroke (AIS). Methods: Eighty-one AIS patients who underwent one-stop CTA-CT perfusion (CTP) from February 2016 to October 2020 were retrospectively reviewed. Single-phase CTA (sCTA) and tMIP CTA were developed from CTP data. Ischemic core (IC) volume, ischemic penumbra volume, and mismatch ratio were calculated. The Tan scale was used for the qualitative evaluation of collateral based on sCTA and tMIP CTA. Quantitative collateral circulation (CCq) parameters were calculated semi-automatically with software by the ratio of the vascular volume (V) on both hemispheres, including tMIP CTA VCCq and sCTA VCCq. Spearman correlation analysis was used to analyze the correlation of collateral-related parameters with final infarct volume (FIV). ROC and multivariable regression analysis were calculated to compare the significance of the above parameters in clinical outcome evaluation. The analysis time of the observers was also compared. Results: tMIP CTA VCCq (r = 0.61, p < 0.01), IC volume (r = 0.66, p < 0.01), Tan score on tMIP CTA (r = 0.52, p < 0.01) and mismatch ratio (r = 0.60, p < 0.01) showed moderate negative correlations with FIV. tMIP CTA VCCq showed the best prognostic value for clinical outcome (AUC = 0.93, p < 0.001), and was an independent predictive factor of clinical outcome (OR = 0.14, p = 0.009). There was no difference in analysis time of tMIP CTA VCCq among observers (p = 0.079). Conclusion: The quantitative evaluation of collateral circulation on tMIP CTA is associated with clinical outcomes in AIS patients with endovascular treatments.

Long noncoding RNA PVT1 acts as an oncogenic driver in human pan-cancer.

Increasing evidence indicates that long noncoding RNAs (lncRNAs) play pivotal roles during tumorigenesis in multiple types of cancers. However, little is known about the exact role of plasmacytoma variant translocation 1 (PVT1) in human pan-cancer. Here, we report the oncogenic role and function of PVT1 in human pan-cancer, including breast cancer. The expression of PVT1 in human tumor tissues and nontumor tissues, the upstream regulation of PVT1 and the relationship between its expression and prognosis and chemoresistance were examined by using The Cancer Genome Atlas data. PVT1 expression is higher in human cancer tissues compared with adjacent noncancerous tissues, and patients with high levels of PVT1 expression usually have tumors with a higher TNM stage. High PVT1 expression is also associated with worse disease outcomes in patients with cancer. Hypomethylation and transcription factor binding in the PVT1 promoter locus activates its transcriptional expression. Guilt by association analysis revealed that PVT1 may be involved in processes associated with tumorigenesis. Moreover, PVT1 may trigger chemoresistance in human cancer. These results indicated that PVT1 may act as an oncogenic driver and maybe a potential therapeutic target in human cancer.

Long noncoding RNA FER1L4 acts as an oncogenic driver in human pan-cancer.

The function of Fer-1 like family member 4 (FER1L4) in human pan-cancer is unknown. Expression of FER1L4 in tumor tissues and nontumor tissues, upstream regulation of FER1L4, and the relationship between its expression with prognosis and chemoresistance were examined by The Cancer Genome Atlas and Gene Expression Omnibus databases. Next, these results were validated in breast tumor and paired nontumor tissues in our cohort. FER1L4 expression is higher in tumor tissues compared with the adjacent nontumor tissues. High FER1L4 expression is associated with worse disease outcomes. Hypomethylation and H3K4me3 accumulation in FER1L4 promoter locus activate its transcriptional expression. Moreover, FER1L4 may trigger chemoresistance in human cancer. Gene Ontology enrichment analysis revealed that FER1L4 may be involved in processes associated with tumorigenesis. These results indicated that FER1L4 may act as an oncogenic driver and it may be a potential therapy target in human cancer.

Parallel Analyses of Somatic Mutations in Plasma Circulating Tumor DNA (ctDNA) and Matched Tumor Tissues in Early-Stage Breast Cancer.

PURPOSE: Early detection and intervention can decrease the mortality of breast cancer significantly. Assessments of genetic/genomic variants in circulating tumor DNA (ctDNA) have generated great enthusiasm for their potential application as clinically actionable biomarkers in the management of early-stage breast cancer.Experimental Design: In this study, 861 serial plasma and matched tissue specimens from 102 patients with early-stage breast cancer who need chemotherapy and 50 individuals with benign breast tumors were deeply sequenced via next-generation sequencing (NGS) techniques using large gene panels. RESULTS: Cancer tissues in this cohort of patients showed profound intratumor heterogeneities (ITHGs) that were properly reflected by ctDNA testing. Integrating the ctDNA detection rate of 74.2% in this cohort with the corresponding predictive results based on Breast Imaging Reporting and Data System classification (BI-RADS) could increase the positive predictive value up to 92% and potentially dramatically reduce surgical overtreatment. Patients with positive ctDNA after surgery showed a higher percentage of lymph node metastasis, indicating potential recurrence and remote metastasis. The ctDNA-positive rates were significantly decreased after chemotherapy in basal-like and Her2+ tumor subtypes, but were persistent despite chemotherapy in luminal type. The tumor mutation burden in blood (bTMB) assessed on the basis of ctDNA testing was positively correlated with the TMB in tumor tissues (tTMB), providing a candidate biomarker warranting further study of its potentials used for precise immunotherapy in cancer. CONCLUSIONS: These data showed that ctDNA evaluation is a feasible, sensitive, and specific biomarker for diagnosis and differential diagnosis of patients with early-stage breast cancer who need chemotherapy.

Prognostic implications of fibroblast growth factor receptor 4 polymorphisms in primary breast cancer.

Fibroblast growth factor receptor 4 (FGFR4) belongs to the receptor tyrosine kinase (RTK) family, and FGFR4 polymorphisms have been implicated in both normal development and cancer, including breast cancer. In the present study, we investigated correlations between polymorphisms in FGFR4 and breast cancer prognosis. The FGFR4 SNPs rs1966265 and rs351855 were genotyped in 747 breast cancer patients using the SNaPshot method. FGFR4 protein expression was detected by immunohistochemistry in 339 samples. SNP rs351855 was correlated with FGFR4 protein expression under dominant and co-dominant models. Lymph node metastasis (LNM), ER (estrogen receptor) status, and molecular subtype were associated with high FGFR4 expression. Univariate analysis revealed rs351855 (CC/CT: P = 0.027, CC/TT: P < 0.001, CC/CT + TT: P = 0.005) to be a prognostic predictor, and multivariate analysis indicated rs351855 (CC/TT: P = 0.005) to be an independent prognostic factor. Kaplan-Meier survival analysis showed that high FGFR4 protein expression was associated with a poor prognosis. SNP rs351855 was correlated with worse outcomes, with a dose-dependent effect. The results of this study show that FGFR4 SNP rs351855 is associated with up-regulation of FGFR4 protein expression and a worse prognosis in breast cancer.

PSAT1 is regulated by ATF4 and enhances cell proliferation via the GSK3ß/ß-catenin/cyclin D1 signaling pathway in ER-negative breast cancer.

BACKGROUND: A growing amount of evidence has indicated that PSAT1 is an oncogene that plays an important role in cancer progression and metastasis. In this study, we explored the expression and function of PSAT1 in estrogen receptor (ER)-negative breast cancer. METHOD: The expression level of PSAT1 in breast cancer tissues and cells was analyzed using real-time-PCR (RT-PCR), TCGA datasets or immunohistochemistry (IHC). The overall survival of patients with ER-negative breast cancer stratified by the PSAT1 expression levels was evaluated using Kaplan-Meier analysis. The function of PSAT1 was analyzed using a series of in vitro assays. Moreover, a nude mouse model was used to evaluate the function of PSAT1 in vivo. qRT-PCR and western blot assays were used to evaluate gene and protein expression, respectively, in the indicated cells. In addition, we demonstrated that PSAT1 was activated by ATF4 by chromatin immunoprecipitation (ChIP) assays. RESULTS: mRNA expression of PSAT1 was up-regulated in ER-negative breast cancer. A tissue microarray that included 297 specimens of ER-negative breast cancer was subjected to an immunohistochemistry assay, which demonstrated that PSAT1 was overexpressed and predicted a poor clinical outcome of patients with this disease. Our data showed that PSAT1 promoted cell proliferation and tumorigenesis in vitro and in vivo. We further found that PSAT1 induced up-regulation of cyclin D1 via the GSK3ß/ß-catenin pathway, which eventually led to the acceleration of cell cycle progression. Furthermore, ATF4 was also overexpressed in ER-negative breast cancers, and a positive correlation between the ATF4 and PSAT1 mRNA levels was observed in ER-negative breast cancers. We further demonstrated that knockdown of ATF4 by siRNA reduced PSAT1 expression. Finally, chromatin immunoprecipitation (ChIP) assays showed that PSAT1 was a target of ATF4. CONCLUSIONS: PSAT1, which is overexpressed in ER-negative breast cancers, is activated by ATF4 and promotes cell cycle progression via regulation of the GSK3ß/ß-catenin/cyclin D1 pathway.

A High-Quality Biobank Supports Breast Cancer Research in Harbin, China.

We established a standard breast cancer biobank at Harbin Medical University Cancer Hospital (HMUCH) in 2009. More than 100,000 biospecimens, including high-quality human breast cancer samples, matched blood samples, and adjacent normal tissues, were collected from patients and healthy donors in HMUCH and were then deposited in the repository. We reported the establishment of a biobank in our hospital and its crucial role in translational medicine research. We stored, processed, and distributed qualified biological specimens in accordance with international standard operating procedures. We also summarized the utilization of this biobank and its influence on research projects over the years since its establishment. Therefore, we can verify specific biomarkers that may aid in the development of targeted breast cancer therapies by using high-quality, well-annotated tissue samples provided by the biobank.

The long non-coding RNA EPB41L4A-AS2 inhibits tumor proliferation and is associated with favorable prognoses in breast cancer and other solid tumors.

EPB41L4A-AS2 is a novel long non-coding RNA of unknown function. In this study, we investigated the expression of EPB41L4A-AS2 in breast cancer tissues and evaluated its relationship with the clinicopathological features and prognosis of patients with breast cancer. This entailed conducting a meta-analysis and prognosis validation study using two cohorts from the Gene Expression Omnibus (GEO). In addition, we assessed EPB41L4A-AS2 expression and its relationship with the clinicopathological features of renal and lung cancers using the Cancer Genome Atlas cohort and a GEO dataset. We also clarified the role of EPB41L4A-AS2 expression in mediating cancer cell proliferation in breast, renal, and lung cancer cell lines transfected with an EPB41L4A-AS2 expression vector. We found that high EPB41L4A-AS2 expression is associated with favorable disease outcomes. Gene ontology enrichment analysis revealed that EPB41L4A-AS2 may be involved in processes associated with tumor biology. Finally, overexpression of EPB41L4A-AS2 inhibited tumor cell proliferation in breast, renal, and lung cancer cell lines. Our clinical and in vitro results suggest that EPB41L4A-AS2 inhibits solid tumor formation and that evaluation of this long non-coding RNA may have prognostic value in the clinical management of such malignancies.

Downregulation of long noncoding RNA MALAT1 induces epithelial-to-mesenchymal transition via the PI3K-AKT pathway in breast cancer.

The metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) regulates cell motility via the transcriptional or post-transcriptional control of motility-related genes. Whether MALAT1 plays a critical role in cancer progression in breast cancer remains unclear. In this study, we found that MALAT1 was downregulated in breast tumor cell lines and cancer tissue, and showed that knockdown of MALAT1 in breast cancer cell lines induced an epithelial-to-mesenchymal transition (EMT) program via phosphatidylinositide-3 kinase-AKT pathways. Furthermore, lower expression of MALAT1 in breast cancer patients was associated with shorter relapse-free survival. Thus, our results indicate for the first time that MALAT1 is a novel regulator of EMT in breast cancer and may be a potential therapeutic target for breast cancer metastasis.

Downregulation of the long noncoding RNA EGOT correlates with malignant status and poor prognosis in breast cancer.

Eosinophil granule ontogeny transcript (EGOT) is a long noncoding RNA involved in the regulation of eosinophil granule protein transcript expression. However, little is known about the role of EGOT in malignant disease. This study aimed to assess the potential role of EGOT in the pathogenesis of breast cancer. Quantitative real-time polymerase chain reaction was performed to detect the expression levels of EGOT in 250 breast cancerous tissues and 50 adjacent noncancerous tissues. The correlation of EGOT expression with clinicopathological features and prognosis was also analyzed. EGOT expression was lower in breast cancer compared with the adjacent noncancerous tissues (P < 0.001), and low levels of EGOT expression were significantly correlated with larger tumor size (P = 0.022), more lymph node metastasis (P = 0.020), and higher Ki-67 expression (P = 0.017). Moreover, patients with low levels of EGOT expression showed significantly worse prognosis for overall survival (P = 0.040), and this result was further validated in a larger cohort from a public database. Multivariate analysis suggested that low levels of EGOT were a poor independent prognostic predictor for breast cancer patients (HR = 1.857, 95 % CI = 1.032-3.340, P = 0.039). In conclusion, EGOT may play an important role in breast cancer progression and prognosis and may serve as a new potential prognostic target in breast cancer patients.