Effects of combined ultrasound and calcium ion pretreatments on polyphenols during mung bean germination: Exploring underlying mechanisms.

Mung beans were pretreated with a combination of ultrasonic and calcium ion to enhance the polyphenol content and antioxidant capacity during germination. Changes in polyphenol content and antioxidant capacity during germination, along with underlying mechanisms, were investigated. Both single ultrasound and combined ultrasound-Ca2+ pretreatments significantly increased the polyphenol content and enhanced the antioxidant capacity (p < 0.05) of mung beans depending on germination period. Among 74 polyphenolic metabolites identified in germinated mung beans, 50 were differential. Notably, 23 of these metabolites showed a significant positive correlation with antioxidant activity. Ultrasound pretreatment promoted flavonoid biosynthesis, whereas ultrasound-Ca2+ pretreatment favored the tyrosine synthesis pathway. Polyphenol composition and accumulation changes were mainly influenced by metabolic pathways like flavonoid, isoflavonoid, anthocyanin, and flavone/flavonol biosynthesis. The results suggest that ultrasound alone or combined with calcium ion pretreatments effectively enhance mung bean polyphenol content and antioxidant capacity during germination.

Advancing Ki67 hotspot detection in breast cancer: a comparative analysis of automated digital image analysis algorithms.

AIM: Manual detection and scoring of Ki67 hotspots is difficult and prone to variability, limiting its clinical utility. Automated hotspot detection and scoring by digital image analysis (DIA) could improve the assessment of the Ki67 hotspot proliferation index (PI). This study compared the clinical performance of Ki67 hotspot detection and scoring DIA algorithms based on virtual dual staining (VDS) and deep learning (DL) with manual Ki67 hotspot PI assessment. METHODS: Tissue sections of 135 consecutive invasive breast carcinomas were immunohistochemically stained for Ki67. Two DIA algorithms, based on VDS and DL, automatically determined the Ki67 hotspot PI. For manual assessment; two independent observers detected hotspots and calculated scores using a validated scoring protocol. RESULTS: Automated hotspot detection and assessment by VDS and DL could be performed in 73% and 100% of the cases, respectively. Automated hotspot detection by VDS and DL led to higher Ki67 hotspot PIs (mean 39.6% and 38.3%, respectively) compared to manual consensus Ki67 PIs (mean 28.8%). Comparing manual consensus Ki67 PIs with VDS Ki67 PIs revealed substantial correlation (r = 0.90), while manual consensus versus DL Ki67 PIs demonstrated high correlation (r = 0.95). CONCLUSION: Automated Ki67 hotspot detection and analysis correlated strongly with manual Ki67 assessment and provided higher PIs compared to manual assessment. The DL-based algorithm outperformed the VDS-based algorithm in clinical applicability, because it did not depend on virtual alignment of slides and correlated stronger with manual scores. Use of a DL-based algorithm may allow clearer Ki67 PI cutoff values, thereby improving the clinical usability of Ki67.

Functional ex vivo DNA fibre assay to measure replication dynamics in breast cancer tissue.

Replication stress (RS) is a key trait of cancer cells, and a potential actionable target in cancer treatment. Accurate methods to measure RS in tumour samples are currently lacking. DNA fibre analysis has been used as a common technique to measure RS in cell lines. Here, we investigated DNA fibre analysis on fresh breast cancer specimens and correlated DNA replication kinetics to known RS markers and genomic alterations. Fresh, treatment-naïve primary breast cancer samples (n = 74) were subjected to ex vivo DNA fibre analysis to measure DNA replication kinetics. Tumour cell proliferation was confirmed by EdU incorporation and cytokeratin AE1/AE3 (CK) staining. The RS markers phospho-S33-RPA and γH2AX and the RS-inducing proto-oncogenes Cyclin E1 and c-Myc were analysed by immunohistochemistry. Copy number variations (CNVs) were assessed from genome-wide single nucleotide polymorphism (SNP) arrays. We found that the majority of proliferating (EdU-positive) cells in each sample were CK-positive and therefore considered to be tumour cells. DNA fibre lengths varied largely in most tumour samples. The median DNA fibre length showed a significant inverse correlation with pRPA expression (r = -0.29, p = 0.033) but was not correlated with Cyclin E1 or c-Myc expression and global CNVs in this study. Nuclear Cyclin E1 expression showed a positive correlation with pRPA levels (r = 0.481, p < 0.0001), while cytoplasmic Cyclin E1 expression exhibited an inverse association with pRPA expression (r = -0.353, p = 0.002) and a positive association with global CNVs (r = 0.318, p = 0.016). In conclusion, DNA fibre analysis performed with fresh primary breast cancer samples is feasible. Fibre lengths were associated with pRPA expression. Cyclin E1 expression was associated with pRPA and the percentage of CNVs. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

RAD52-dependent mitotic DNA synthesis is required for genome stability in Cyclin E1-overexpressing cells.

Overexpression of Cyclin E1 perturbs DNA replication, resulting in DNA lesions and genomic instability. Consequently, Cyclin E1-overexpressing cancer cells increasingly rely on DNA repair, including RAD52-mediated break-induced replication during interphase. We show that not all DNA lesions induced by Cyclin E1 overexpression are resolved during interphase. While DNA lesions upon Cyclin E1 overexpression are induced in S phase, a significant fraction of these lesions is transmitted into mitosis. Cyclin E1 overexpression triggers mitotic DNA synthesis (MiDAS) in a RAD52-dependent fashion. Chemical or genetic inactivation of MiDAS enhances mitotic aberrations and persistent DNA damage. Mitosis-specific degradation of RAD52 prevents Cyclin E1-induced MiDAS and reduces the viability of Cyclin E1-overexpressing cells, underscoring the relevance of RAD52 during mitosis to maintain genomic integrity. Finally, analysis of breast cancer samples reveals a positive correlation between Cyclin E1 amplification and RAD52 expression. These findings demonstrate the importance of suppressing mitotic defects in Cyclin E1-overexpressing cells through RAD52.

cGAS-STING pathway expression correlates with genomic instability and immune cell infiltration in breast cancer.

Genomic instability, as caused by oncogene-induced replication stress, can lead to the activation of inflammatory signaling, involving the cGAS-STING and JAK-STAT pathways. Inflammatory signaling has been associated with pro-tumorigenic features, but also with favorable response to treatment, including to immune checkpoint inhibition. In this study, we aim to explore relations between inflammatory signaling, markers of replication stress, and immune cell infiltration in breast cancer. Expression levels of cGAS-STING signaling components (STING, phospho-TBK1, and phospho-STAT1), replication stress markers (γH2AX and pRPA), replication stress-related proto-oncogenes (Cyclin E1 and c-Myc) and immune cell markers (CD20, CD4, and CD57) are determined immunohistochemically on primary breast cancer samples (n = 380). RNA-sequencing data from TCGA (n = 1082) and METABRIC (n = 1904) are used to calculate cGAS-STING scores. pTBK1, pSTAT1 expression and cGAS-STING pathway scores are all increased in triple-negative breast cancers compared to other subtypes. Expression of γH2AX, pRPA, Cyclin E1, c-Myc, and immune cell infiltration positively correlate with p-STAT1 expression (P < 0.001). Additionally, we observe significant positive associations between expression of pTBK1 and γH2AX, pRPA, c-Myc, and number of CD4+ cells and CD20+ cells. Also, cGAS-STING scores are correlated with genomic instability metrics, such as homologous recombination deficiency (P < 0.001) and tumor mutational burden (P < 0.01). Moreover, data from the I-SPY2 clinical trial (n = 71) confirms that higher cGAS-STING scores are observed in breast cancer patients who responded to immunotherapy combined with chemotherapy. In conclusion, the cGAS-STING pathway is highly expressed in TNBCs and is correlated with genomic instability and immune cell infiltration.

PPM1D activity promotes the replication stress caused by cyclin E1 overexpression.

Oncogene-induced replication stress has been recognized as a major cause of genome instability in cancer cells. Increased expression of cyclin E1 caused by amplification of the CCNE1 gene is a common cause of replication stress in various cancers. Protein phosphatase magnesium-dependent 1 delta (PPM1D) is a negative regulator of p53 and has been implicated in termination of the cell cycle checkpoint. Amplification of the PPM1D gene or frameshift mutations in its final exon promote tumorigenesis. Here, we show that PPM1D activity further increases the replication stress caused by overexpression of cyclin E1. In particular, we demonstrate that cells expressing a truncated mutant of PPM1D progress faster from G1 to S phase and fail to complete licensing of the replication origins. In addition, we show that transcription-replication collisions and replication fork slowing caused by CCNE1 overexpression are exaggerated in cells expressing the truncated PPM1D. Finally, replication speed and accumulation of focal DNA copy number alterations caused by induction of CCNE1 expression was rescued by pharmacological inhibition of PPM1D. We propose that increased activity of PPM1D suppresses the checkpoint function of p53 and thus promotes genome instability in cells expressing the CCNE1 oncogene.

Deciphering the role of QPCTL in glioma progression and cancer immunotherapy.

Background: Glioma is the most lethal and most aggressive brain cancer, and currently there is no effective treatment. Cancer immunotherapy is an advanced therapy by manipulating immune cells to attack cancer cells and it has been studied a lot in glioma treatment. Targeting the immune checkpoint CD47 or blocking the CD47-SIRPα axis can effectively eliminate glioma cancer cells but also brings side effects such as anemia. Glutaminyl-peptide cyclotransferase-like protein (QPCTL) catalyzes the pyroglutamylation of CD47 and is crucial for the binding between CD47 and SIRPα. Further study found that loss of intracellular QPCTL limits chemokine function and reshapes myeloid infiltration to augment tumor immunity. However, the role of QPCTL in glioma and the relationship between its expression and clinical outcomes remains unclear. Deciphering the role of QPCTL in glioma will provide a promising therapy for glioma cancer immunotherapy. Methods: QPCTL expression in glioma tissues and normal adjacent tissues was primarily analyzed in The Cancer Genome Atlas (TCGA) database, and further validated in another independent cohort from the Gene Expression Omnibus (GEO) database, Chinese Glioma Genome Atlas (CGGA), and Human Protein Atlas (HPA). The relationships between QPCTL expression and clinicopathologic parameters and overall survival (OS) were assessed using multivariate methods and Kaplan-Meier survival curves. And the proteins network with which QPCTL interacted was built using the online STRING website. Meanwhile, we use Tumor Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA) databases to investigate the relationships between QPCTL expression and infiltrated immune cells and their corresponding gene marker sets. We analyzed the Differentially Expressed Genes (DEGs) including GO/KEGG and Gene Set Enrichment Analysis (GSEA) based on QPCTL-high and -low expression tumors. Results: In contrast to normal tissue, QPCTL expression was higher in glioma tumor tissue (p < 0.05). Higher QPCTL expression was closely associated with high-grade malignancy and advanced tumor stage. Univariate and multivariate analysis indicated the overall survival of glioma patients with higher QPCTL expression is shorter than those with lower QPCTL expression (p < 0.05). Glioma with QPCTL deficiency presented the paucity of infiltrated immune cells and their matching marker sets. Moreover, QPCTL is essential for glioma cell proliferation and tumor growth and is a positive correlation with glioma cell stemness. Conclusion: High QPCTL expression predicts high grades of gliomas and poor prognosis with impaired infiltration of adaptive immune cells in the tumor microenvironment as well as higher cancer stemness. Moreover, targeting QPCTL will be a promising immunotherapy in glioma cancer treatment.

An Overview: The Diversified Role of Mitochondria in Cancer Metabolism.

Mitochondria are intracellular organelles involved in energy production, cell metabolism and cell signaling. They are essential not only in the process of ATP synthesis, lipid metabolism and nucleic acid metabolism, but also in tumor development and metastasis. Mutations in mtDNA are commonly found in cancer cells to promote the rewiring of bioenergetics and biosynthesis, various metabolites especially oncometabolites in mitochondria regulate tumor metabolism and progression. And mutation of enzymes in the TCA cycle leads to the unusual accumulation of certain metabolites and oncometabolites. Mitochondria have been demonstrated as the target for cancer treatment. Cancer cells rely on two main energy resources: oxidative phosphorylation (OXPHOS) and glycolysis. By manipulating OXPHOS genes or adjusting the metabolites production in mitochondria, tumor growth can be restrained. For example, enhanced complex I activity increases NAD+/NADH to prevent metastasis and progression of cancers. In this review, we discussed mitochondrial function in cancer cell metabolism and specially explored the unique role of mitochondria in cancer stem cells and the tumor microenvironment. Targeting the OXPHOS pathway and mitochondria-related metabolism emerging as a potential therapeutic strategy for various cancers.

Unstable platform training in tennis players / Treinamento em plataforma instável em tenistas / Entrenamiento en plataforma inestable en tenistas

ABSTRACT Introduction: The constant maintenance of muscular strength is a highly relevant care in training for tennis practice. The unstable platform is developed with the improvement of modern and technological resources, and the need to verify its effects on the athletes' physical fitness is requested. Objective: Study the effect of unstable platform training on tennis players' balance ability and assertiveness. Methods: 12 male tennis-practicing students of the Beijing Sports University School of Education 2020 class were randomly selected as research volunteers. Through a literature search, data statistics, and other methods, they were randomly divided into an experimental group and a control group. After 6 weeks of traditional training in the control group and the addition of unstable platform balance training in the experimental group, the results were compared. Results: The ability to stand with eyes open on the dominant leg was significantly improved in the experimental group. After routine training and balance training, the athletes in the experimental group had a great improvement in the assertiveness of passes (P<0.05), and the stability of the service was also improved (P<0.05). Conclusion: After training, all physical abilities were improved. The unstable platform training is a valid resource to improve athletes' balance and assertiveness ability. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: A constante manutenção da força muscular é um cuidado altamente relevante no treinamento para a prática do tênis. A plataforma instável é desenvolvida com o aperfeiçoamento de recursos modernos e tecnológicos e a necessidade de verificar os seus efeitos sobre a aptidão física dos atletas é requisitada. Objetivo: Estudar o efeito do treinamento em plataforma instável sobre a capacidade de equilíbrio e assertividade dos tenistas. Métodos: Um total de 12 estudantes masculinos praticantes de tênis da classe 2020 da Escola de Educação da Universidade Esportiva de Beijing foram selecionados aleatoriamente como voluntários de pesquisa. Através de pesquisas bibliográficas, estatísticas de dados e outros métodos, eles foram divididos aleatoriamente em grupo experimental e grupo controle. Após 6 semanas de treinamento tradicional ao grupo controle e a adição de um treinamento de equilíbrio em plataforma instável no grupo experimental, comparou-se os resultados. Resultados: A capacidade de ficar em pé com os olhos abertos sobre a perna dominante foram significativamente aprimorados no grupo experimental. Após o treinamento de rotina e o treinamento de equilíbrio, os atletas do grupo experimental tiveram uma grande melhora na assertividade dos passes (P<0,05), e a estabilidade do saque também foi aprimorada(P<0,05). Conclusão: Após o treinamento, todas as habilidades físicas foram melhoradas. O treinamento em plataforma instável é um recurso válido para aprimorar a capacidade de equilíbrio e assertividade dos atletas. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: El mantenimiento constante de la fuerza muscular es un cuidado muy relevante en el entrenamiento para la práctica del tenis. La plataforma inestable se desarrolla con la mejora de los recursos modernos y tecnológicos y se solicita la comprobación de sus efectos sobre la aptitud física de los deportistas. Objetivo: Estudiar el efecto del entrenamiento en plataforma inestable sobre la capacidad de equilibrio y asertividad de los tenistas. Métodos: Un total de 12 estudiantes varones practicantes de tenis de la clase 2020 de la Escuela de Educación de la Universidad de Deportes de Pekín fueron seleccionados al azar como voluntarios para la investigación. Mediante la búsqueda de literatura, la estadística de datos y otros métodos, se dividieron aleatoriamente en grupo experimental y grupo de control. Tras 6 semanas de entrenamiento tradicional en el grupo de control y la adición del entrenamiento de equilibrio en plataforma inestable en el grupo experimental, se compararon los resultados. Resultados: La capacidad de mantenerse en pie con los ojos abiertos sobre la pierna dominante mejoró significativamente en el grupo experimental. Después del entrenamiento de rutina y del entrenamiento de equilibrio, los atletas del grupo experimental tuvieron una gran mejora en el asertividad de los pases (P<0,05), y también mejoró la estabilidad del saque (P<0,05). Conclusión: Tras el entrenamiento, todas las capacidades físicas mejoraron. El entrenamiento en plataforma inestable es un recurso válido para mejorar la capacidad de equilibrio y asertividad de los deportistas. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Mining the prognostic significance and immune infiltration of STAT family members in human breast cancer by bioinformatics analysis.

Background: Growing evidence proved that signal transducer and activators of transcription (STAT) proteins are cytoplasmic transcription factors known to play key roles in many cellular biological processes and may be prognostic predictors of some cancers. However, the role of each STAT family members in breast cancer (BRCA) is diverse and controversial. This study aimed to systematic mine the prognostic significance and immune infiltration of STAT family member in human BRCA. Methods: Based on The Cancer Genome Atlas (TCGA) database, we used the Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA) and The Human Protein Atlas to analyze the expression of STAT family members in normal human breast and tumor tissues. The Kaplan-Meier Plotter, GEPIA and PrognoScan were utilized to assess the prognostic value of different STATs in BRCA. Then we used the cBioPortal, STRING, GeneMANIA and Metascape to make further mutation analysis, protein-protein interaction (PPI) analysis and subsequent functional enrichment analysis. Finally, the "ESTIMATE" and "ggcorrplot" package of R 17 software were used for immune infiltration analysis. Results: STAT2 [P<0.01, hazard ratio (HR) =1.23, 95% confidence interval (CI): 1.07-1.42] and STAT3 (P=0.018, HR =0.69, 95% CI: 0.51-0.94) could be an independent risk factor for predicting overall survival (OS). STAT4 could be used as an independent predictor of distant metastasis-free survival in BRCA based on both GSE19615 (P=0.021, HR =0.21, 95% CI: 0.06-0.79) and GSE2034 (P=0.015, HR =0.57, 95% CI: 0.37-0.90) datasets. Meanwhile, STAT5A, STAT5B and STAT6 also have been shown to independently predict the prognosis of BRCA. Additionally, the functional mechanisms of STAT4 co-expressed genes were mainly focused on immune-related pathways and its expression was associated with immune checkpoint-associated genes and immunomodulators in BRCA. Conclusions: Our study mined the prognostic significance of STAT family members in BRCA and their correlation with immune infiltration. The results suggest that individual STATs, except STAT1, may act as a prognostic biomarker for BRCA and provide a reference for further potential immunotherapies.

A novel immune subtype classification of ER-positive, PR-negative and HER2-negative breast cancer based on the genomic and transcriptomic landscape.

BACKGROUND: The diversity and plasticity behind ER+/PR-/HER2- breast cancer have not been widely explored. It is essential to identify heterogeneous microenvironment phenotypes and investigate specific genomic events driving the formation of these phenotypes. METHODS: Based on the immune-related gene expression profiles of 411 ER+/PR-/HER2- breast cancers in the METABRIC cohort, we used consensus clustering to identify heterogeneous immune subtypes and assessed their reproducibility in an independent meta-cohort including 135 patients collected from GEO database. We further analyzed the differences of cellular and molecular characteristics, and potential immune escape mechanism among immune subtypes. In addition, we constructed a transcriptional trajectory to visualize the distribution of individual patient. RESULTS: Our analysis identified and validated five reproducible immune subtypes with distinct cellular and molecular characteristics, potential immune escape mechanisms, genomic drivers, as well as clinical outcomes. An immune-cold subtype, with the least amount of lymphocyte infiltration, had a poorer prognosis. By contrast, an immune-hot subtype, which demonstrated the highest infiltration of CD8+ T cells, DCs and NK cells, and elevated IFN-γ response, had a comparatively favorable prognosis. Other subtypes showed more diverse gene expression and immune infiltration patterns with distinct clinical outcomes. Finally, our analysis revealed a complex immune landscape consisting of both discrete cluster and continuous spectrum. CONCLUSION: Overall, this study revealed five heterogeneous immune subtypes among ER+/PR-/HER2- breast cancer, also provided important implications for clinical translations.

Studying the pathological and biochemical features in breast cancer progression by confocal Raman microspectral imaging of excised tissue samples.

Confocal Raman microspectral imaging (CRMI) has been used to detect the spectra-pathological features of ductal carcinoma in situ (DCIS) and lobular hyperplasia (LH) compared with the heathy (H) breast tissue. A total of 15-20 spectra were measured from healthy tissue, LH tissue, and DCIS tissue. One-way ANOVA and Tukey's honest significant difference (HSD) post hoc multiple tests were used to evaluate the peak intensity variations in all three tissue types. Besides that, linear discrimination analysis (LDA) algorithm was adopted in combination with principal component analysis (PCA) to classify the spectral features from tissues at different stages along the continuum to breast cancer. Moreover, by using the point-by-point scanning methodology, spectral datasets were obtained and reconstructed for further pathologic visualization by multivariate imaging methods, including K-mean clustering analysis (KCA) and PCA. Univariate imaging of individual Raman bands was also used to describe the differences in the distribution of specific molecular components in the scanning area. After a detailed spectral feature analysis from 800 to 1800 cm-1 and 2800 to 3000 cm-1 for all the three tissue types, the histopathological features were visualized based on the content and structural variations of lipids, proteins, phenylalanine, carotenoids and collagen, as well as the calcification phenomena. The results obtained not only allowed a detailed Raman spectroscopy-based understanding of the malignant transformation process of breast cancer, but also provided a solid spectral data support for developing Raman based breast cancer clinical diagnostic techniques.

A nomogram based on CENPP expression for survival prediction in breast cancer.

BACKGROUND: In recent years, it has been found that the expression of 17 centromere proteins (CENPs) was closely related to malignant tumors, however, the role of CENPs in breast cancer (BC) has not been fully investigated. This study intends to investigate the prognostic value of CENPs in BC and establish nomogram based on expression of CENPs to predict BC patients' prognosis. METHODS: A total of 800 BC patients with complete relevant data were included from the TCGA database and were further randomly divided into training set (N=480) and validation set (N=320). Univariate and multivariate Cox regression analysis were used to screen independent factors for overall survival (OS) prediction of BC patients in the training set. Then, the nomogram was established based on these independent predictors and further validated by receiver-operating characteristic (ROC) curves and calibration plots. The GEPIA and bcGenExMiner v4.4 databases were utilized to analyze mRNA expression of candidate gene in BC patients with different clinicopathological features, respectively. RESULTS: Multivariate Cox regression analysis showed that age, Her2 status, pathologic_T stage, pathologic_M stage and CENPP expression were of independent prognostic value for BC. CENPP was overexpressed in BC tissues (P<0.01) and lower expression of CENPP was associated with worse OS (P=0.005, HR =2.35; 95% CI: 1.30-4.23). We then established a nomogram based on those independent predictors, and the calibration curve demonstrated good fitness of the nomogram for OS prediction. In the training set, the AUCs of 3- and 5-year survival were 0.757 and 0.797, respectively. In the validation set, the AUCs of 3- and 5-year survival were 0.727 and 0.71, respectively. CONCLUSIONS: Our study showed that CENPP was a novel prognostic factor for patients with BC, and the established nomogram could provide valuable information on prognostic prediction for patients with BC.

A Novel Ferroptosis-Related Gene Signature for Overall Survival Prediction in Patients With Breast Cancer.

INTRODUCTION: Breast cancer is the most common malignant tumor in women worldwide. However, advanced multidisciplinary therapy cannot rescue the mortality of high-risk breast cancer metastasis. Ferroptosis is a newly discovered form of regulating cell death that related to cancer treatment, especially in eradicating aggressive malignancies that are resistant to traditional therapies. However, the prognostic value of ferroptosis-related gene in breast cancer remains unknown. MATERIALS AND METHODS: In this study, a total of 1,057 breast cancer RNA expression data with clinical and follow-up information were downloaded from the TCGA cohort, multivariate Cox regression was used to construct the 11-gene prognostic ferroptosis-related gene signature. The breast cancer patients from the GEO cohort were used for validation. The expression levels of core prognostic genes were also verified in erastin-treated breast cancer cell lines by real-time polymerase chain action (PCR). RESULTS AND DISCUSSION: Our results showed that 78% ferroptosis-related genes were differentially expressed between breast cancer tumor tissue and adjacent non-tumorous tissues, including 29 of them which were significantly correlated with OS in the univariate Cox regression analysis. Patients were divided into high-risk group and low-risk group by the 11-gene signature. Patients with high-risk scores had a higher probability of death earlier than the low-risk group both in the TCGA construction cohort and in the GEO validation cohort (all P < 0.001). Meanwhile, the risk score was proved to be an independent predictor for OS in both univariate and multivariate Cox regression analyses (HR > 1, P < 0.01). The predictive efficacy of the prognostic signature for OS was further verified by the time-dependent ROC curves. Moreover, we also enriched many immune-related biological processes in later functional analysis; the immune status showed a statistical difference between the two risk groups. In addition, the differences in expression levels of 11 core prognostic genes were examined in ferroptosis inducer-treated breast cancer cell lines. CONCLUSION: In conclusion, a novel ferroptosis-related gene model can be used for prognostic prediction in breast cancer. New ferroptosis-related genes may be used for breast cancer targeting therapy in the future.

A systematic analysis of a potential metabolism-related prognostic signature for breast cancer patients.

BACKGROUND: Metabolic pathways play an essential role in breast cancer. However, the role of metabolism-related genes in the early diagnosis of breast cancer remains unknown. METHODS: In our study, RNA sequencing (RNA-seq) expression data and clinicopathological information from The Cancer Genome Atlas (TCGA) and GSE20685 were obtained. Univariate cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses were performed on the differentially expressed metabolism-related genes. Then, the formula of the metabolism-related risk model was composed, and the risk score of each patient was calculated. The breast cancer patients were divided into high-risk and low-risk groups with a cutoff of the median expression value of the risk score, and the prognostic analysis was also used to analyze the survival time between these two groups. In the end, we also analyzed the expression, interaction, and correlation among genes in the metabolism-related gene risk model. RESULTS: The results from the prognostic analysis indicated that the survival was significantly poorer in the high-risk group than in the low-risk group in both TCGA and GSE20685 datasets. In addition, after adjusting for different clinicopathological features in multivariate analysis, the metabolism-related risk model remained an independent prognostic indicator in TCGA dataset. CONCLUSIONS: In summary, we systematically developed a potential metabolism-related gene risk model for predicting prognosis in breast cancer patients.

Major Postoperative Complications in Esophageal Cancer After Minimally Invasive Esophagectomy Compared With Open Esophagectomy: An Updated Meta-analysis.

BACKGROUND: To evaluate the existing literature comparing cardiopulmonary complications after minimally invasive esophagectomy (MIE) with open esophagectomy (OE) and conduct a meta-analysis based on the relevant studies. METHODS: A systematic search for articles was performed in Medline, Embase, Wiley Online Library, and the Cochrane Library. The relative risks or odds ratios (ORs) were calculated by using fixed or random-effects models. The I2 and X2 tests were used to test for statistical heterogeneity. We performed a metaregression for the pulmonary complications with the adenocarcinoma proportion and tumor stage. Publication bias and small-study effects were assessed using Egger's test and Begg's funnel plot. RESULTS: A total of 30,850 participants were enrolled in the 63 studies evaluated in the meta-analysis. Arrhythmia, pulmonary embolism, pulmonary complications, gastric tip necrosis, anastomotic leakage, and vocal cord palsy were chosen as outcomes. The occurrence rate of arrhythmia was significantly lower in patients receiving MIE than in patients receiving OE (OR = 0.69; 95% CI = 0.53-0.89), with heterogeneity (I2 = 30.7%, P = 0.067). The incidence of pulmonary complications was significantly lower in patients receiving MIE (OR = 0.54, 95% CI = 0.45-0.63) but heterogeneity remained (I2 = 72.1%, P = 0.000). The risk of gastric tip necrosis (OR = 1.48, 95% CI = 1.07-2.05) after OE was lower than that after MIE. Anastomotic leakage, pulmonary embolism, and vocal cord palsy showed no significant differences between the two groups. CONCLUSIONS: MIE has advantages over OE, especially in reducing the incidence of arrhythmia and pulmonary complications. Thus, MIE can be recommended as the preferred alternative surgery method for resectable esophageal cancer.

Loss of HOXB3 correlates with the development of hormone receptor negative breast cancer.

BACKGROUND: The homeobox gene family, encoding a specific nuclear protein, is essential for embryonic development, differentiation, and homeostasis. The role of the HOXB3 protein varies in different tumors. This study aims to explore the role of the HOXB3 gene in breast cancer. METHOD: Differentially expressed genes were screened by analyzing metastatic breast cancer gene chip data from TCGA and GEO databases. The function of the selected HOXB3 gene was also analyzed in different databases and through molecular biology methods, such as qRT-PCR, western blot and IF to verify bioinformatics findings. RESULTS: Both bioinformatics analyses and western blot showed that HOXB3 was lost in breast cancer compared to normal breast tissue. Survival analysis also showed that lower expression of HOXB3 was associated with poor prognosis. Bioinformatics analyses further showed that HOXB3 was positively correlated with hormone receptors. Metascape for GO analysis of GEO data provided possible mechanisms that HOXB3 could positively regulate cell adhesion, inhibit cell proliferation and activate immune response in breast cancer; moreover, GSEA included several cancer-associated pathways. CONCLUSION: In summary, HOXB3 expression was decreased in breast cancer, and it was associated with poor prognosis. It might become a new biomarker to predict prognosis of breast cancer.

Pan-Cancer Analysis of the Mitophagy-Related Protein PINK1 as a Biomarker for the Immunological and Prognostic Role.

INTRODUCTION: The PINK1 gene encodes a serine/threonine protein kinase that localizes to mitochondria and has usually been considered to protect cells from stress-induced mitochondrial dysfunction. PINK1 mutations have been observed to lead to autosomal recessive Parkinson's disease. However, the immunological and prognostic roles of PINK1 across cancers remain unclear. MATERIAL AND METHOD: In the current study, we used multiple databases, including Oncomine, PrognoScan, Kaplan-Meier Plotter, GEPIA, TIMER, and cBioportal, to investigate the PINK1 expression distribution and its immunological and prognostic role across cancers. RESULTS AND DISCUSSION: Bioinformatics data revealed that the mRNA expression of PINK1 was downregulated in most tumors. Although there was a significant prognostic value of PINK1 expression across cancers, PINK1 played a protective or detrimental role in different kinds of cancers. Liver hepatocellular carcinoma and lung squamous cell carcinoma were selected as representative cancer types for further exploration. We found that PINK1 always played a protective role in liver hepatocellular carcinoma patients in the stratified prognostic analyses of clinicopathological characteristics. There were contradictory results between liver hepatocellular carcinoma and lung squamous cell carcinoma in the correlations of PINK1 expression with immune infiltration, including infiltration of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells. Furthermore, specific markers of B cells and CD8+ T cells also exhibited different PINK1-related immune infiltration patterns. In addition, there was a significant association between PINK1 copy number variations and immune infiltrates across cancers. CONCLUSION: The mitophagy-related protein PINK1 can work as a biomarker for prognosis and the immune response across cancers.

Mining the prognostic significance of the GINS2 gene in human breast cancer using bioinformatics analysis.

A number of studies have demonstrated the crucial functions of GINS2 within the GINS complex in various types of cancer. However, the molecular mechanisms and prognostic value of GINS2 in breast cancer remain unknown. The present study used; BC-GenExMiner, COSMIC, UCSC Xena, The Human Protein Atlas, GEPIA, cBioPortal, GeneMANIA, TIMER and Oncomine, in order to investigate gene expression, co-expression, clinical parameters and mutations in GINS2 in patients with breast cancer. Furthermore, the present study assessed the prognostic value of GINS2 in patients with breast cancer via the Kaplan-Meier plotter database. The results of the present study demonstrated that the mRNA levels of GINS2 were significantly higher in breast cancer tissue compared with normal tissue. In addition, high mRNA expression levels of GINS2 were associated with high Scarff-Bloom-Richardson status grades, a basal-like status and age (≤51 years); however, it was not associated with lymph node metastasis. The survival analysis revealed that increased GINS2 mRNA levels were associated with a worse prognosis for relapse-free survival in all patients with breast cancer, particularly in those with estrogen receptor-positive and progesterone receptor-positive subtypes. In addition, a positive association between the GINS2, CENPM and MCM4 genes was confirmed. The results of the present study suggest that GINS2 could be used as a potential prognostic biomarker for breast cancer. Nevertheless, further studies are necessary to confirm the effects of GINS2 on the pathogenesis and development of patients with breast cancer.

Increased SIX-1 expression promotes breast cancer metastasis by regulating lncATB-miR-200s-ZEB1 axis.

Patients with advanced breast cancer (BC) showed a higher incidence of regional and distant metastases. Sine oculis homeobox homolog 1 (SIX-1) has been confirmed to be a key tumorigenic and metastatic regulator in BC progression. Yet, molecular mechanisms behind SIX-1-induced BC metastases remain largely unknown. Here we found that SIX-1 was frequently up-regulated in BC and correlated with poor outcomes when tested in human BC tissue microarray. Then, we manipulated the expression of SIX-1 by via shRNA-mediated knockdown and lentivirus-mediated overexpression. Transwell assay in vitro and lung metastases model of nude mice in vivo showed that SIX-1 promoted BC cell invasion and migration in vitro, and facilitated metastases in vivo. Mechanistically, SIX-1 could promote the transcription of lncATB, which exerts critical pro-metastatic role in BC by directly binding to the miR-200 family, especially for miR-200c, to induce EMT and promote metastases. In conclusion, SIX-1 exerts its pro-metastatic role in BC through lncATB/miR-200s axis of EMT signalling pathway and could act as an important diagnostic marker as well as a significant therapeutic target for clinically advanced BC.