Impact of NDUFAF6 on breast cancer prognosis: linking mitochondrial regulation to immune response and PD-L1 expression.

BACKGROUND: Breast cancer is a major global health concern, and there is a continuous search for novel biomarkers to predict its prognosis. The mitochondrial protein NDUFAF6, previously studied in liver cancer, is now being investigated for its role in breast cancer. This study aims to explore the expression and functional significance of NDUFAF6 in breast cancer using various databases and experimental models. METHODS: We analyzed breast cancer samples from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Human Protein Atlas (HPA) databases, supplemented with immunohistochemistry (IHC) staining to assess NDUFAF6 expression. A breast cancer cell xenograft mouse model was used to evaluate tumor growth, apoptosis, and NDUFAF6 expression. Survival probabilities were estimated through Kaplan-Meier plots and Cox regression analysis. A Protein-Protein Interaction (PPI) network was constructed, and differentially expressed genes related to NDUFAF6 were analyzed using GO, KEGG, and GSEA. The relationship between NDUFAF6 expression, immune checkpoints, and immune infiltration was also evaluated. RESULTS: NDUFAF6 was found to be overexpressed in breast cancer patients and in the xenograft mouse model. Its expression correlated with worse clinical features and prognosis. NDUFAF6 expression was an independent predictor of breast cancer outcomes in both univariate and multivariate analyses. Functionally, NDUFAF6 is implicated in several immune-related pathways. Crucially, NDUFAF6 expression correlated with various immune infiltrating cells and checkpoints, particularly promoting PD-L1 expression by inhibiting the NRF2 signaling pathway. CONCLUSION: The study establishes NDUFAF6 as a potential prognostic biomarker in breast cancer. Its mechanism of action, involving the inhibition of NRF2 to upregulate PD-L1, highlights its significance in the disease's progression and potential as a target for immunotherapy.

SPACA6P-AS: a trailblazer in breast cancer pathobiology and therapeutics.

OBJECTIVE: The primary objective of this investigation is to delve into the involvement of the long noncoding RNA (lncRNA) SPACA6P-AS in breast cancer (BC) development, focusing on its expression pattern, association with clinical-pathological features, impact on prognosis, as well as its molecular and immunological implications. METHODS: Bioinformatics analysis was conducted utilizing RNA sequencing data of 1083 BC patients from the TCGA database. Functional exploration of SPACA6P-AS was carried out through the construction of survival curves, GO and KEGG enrichment analysis, and single-sample gene set enrichment analysis (ssGSEA). Furthermore, its functionality was validated through in vitro cell experiments and in vivo nude mouse model experiments. RESULTS: SPACA6P-AS showed a remarkable increase in expression levels in BC tissues (p < 0.001) and demonstrated a close relationship to poor prognosis (overall survival HR = 1.616, progression-free interval HR = 1.40, disease-specific survival HR = 1.54). Enrichment analysis revealed that SPACA6P-AS could impact biological functions such as protease regulation, endopeptidase inhibitor activity, taste receptor activity, taste transduction, and maturity-onset diabetes of the young pathway. ssGSEA analysis indicated a negative correlation between SPACA6P-AS expression and immune cell infiltration like dendritic cells and neutrophils, while a positive correlation was observed with central memory T cells and T helper 2 cells. Results from in vitro and in vivo experiments illustrated that silencing SPACA6P-AS significantly inhibited the proliferation, migration, and invasion capabilities of BC cells. In vitro experiments also highlighted that dendritic cells with silenced SPACA6P-AS exhibited enhanced capabilities in promoting the proliferation of autologous CD3 + T cells and cytokine secretion. These discoveries elucidate the potential multifaceted roles of SPACA6P-AS in BC, including its potential involvement in modulating immune cell infiltration in the tumor microenvironment. CONCLUSION: The high expression of lncRNA SPACA6P-AS in BC is closely linked to poor prognosis and may facilitate tumor progression by influencing specific biological processes, signaling pathways, and the immune microenvironment. The regulatory role of SPACA6P-AS positions it as a prospective biomarker and target for therapeutic approaches for BC diagnosis and intervention.

Adipocyte-derived exosomes promote the progression of triple-negative breast cancer through circCRIM1-dependent OGA activation.

Triple-negative breast cancer (TNBC) has an escalating morbidity and a dismal prognosis. Obesity has been reported to be strongly linked to adverse TNBC outcomes. Exosomes (Exos) transport RNA and proteins between cells and serve as intermediaries for cell-to-cell communication. Accumulated evidence suggests that adipose-secreted circular RNAs (circRNAs) can modulate protein glycosylation in TNBC to facilitate tumor cell outgrowth. Herein, exo-circCRIM1 expression was found to be elevated in TNBC patients with a high body fat percentage. Functional experiments demonstrated that by inhibiting miR-503-5p, exo-circCRIM1 enhanced TNBC evolution and metastasis while activating glycosylation hydrolase OGA. Furthermore, OGA negatively regulates FBP1 by decreasing its protein stability. Moreover, the levels of OGA and FBP1 were positively related to the infiltration level of some immune cells in TNBC. These findings indicate that exo-cirCRIM1 secreted by adipocytes contributes to TNBC progression by inhibiting miR-503-5p and activating the OGA/FBP1 signaling pathway. The findings reveal a novel intercellular signaling pathway mediated by adipose-derived exosomes and suggest that treatment targeting the secreted exosome-circCRIM1 may reverse TNBC progression.

Survival Benefits of Ganoderma Lucidum in Early-stage Triple-negative Breast Cancer: A Real World Study.

BACKGROUND: Ganoderma lucidum extracts are widely used as adjuvants in the treatment of triple-negative breast cancers (TNBC) in China. However, its clinical value in TNBC remains unclear. Therefore, we investigated the clinical effect of Ganoderma lucidum spore powder (GLSP) on prognosis in patients with early-stage TNBC in this study. METHODS: A total of 388 patients who were diagnosed with TNBC at the Sun Yat-sen University Cancer Center from February 2012 to December 2017 were retrospectively reviewed. The propensity score matching (PSM) method was applied to balance baseline data. Kaplan-Meier method and Cox proportional hazards model were used to evaluate the relationship between GLSP and prognosis. RESULTS: Of the 388 patients, 72 (18.6%) patients took GLSP. After PSM, 208 patients were selected for analysis, including 71 (34.1%) patients who took the powder. The median followup period was 51 months. The patients who took GLSP (the treatment group) and those who did not take GLSP (the control group) were similar in most clinico-pathological features before being matched. However, the proportion of patients who received breast-conserving surgery in the treatment group was higher (27.8% vs. 16.1%; p =0.021) than in the control group. No significant difference was found in the baseline data between the two groups for the matched cohort (all p >0.05). Univariate analysis and multivariate analysis showed that patients taking GLSP benefited from improved overall survival (OS) (HR=0.159, p = 0.002) and disease-free survival (DFS) (HR=0.232, p = 0.005) before being matched. The main result of the survival analysis after matching was similar to that described above. Patients in the treatment group achieved both greater OS and DFS benefits than patients in the control group (all p < 0.05). In stratified analysis according to TNM stages, after adjusting for the significant prognostic factors, multivariate analysis revealed that the treatment group had better OS than the control group for patients in stages II and III (HR=0.172, p =0.004). CONCLUSIONS: The results of this real-world propensity-score-matched study suggest that GLSP can improve OS and DFS in early-stage TNBC patients. A higher OS was observed for patients taking GLSP, particularly in stage II and stage III.

An empirical study on learners' learning emotion and learning effect in offline learning environment.

The application of non-cognitive factors represented by facial emotion in educational evaluation has attracted much attention in recent years. There are many existing studies on facial emotion assisted education evaluation, but most of them are based on virtual learning environments, which means that the research on facial emotion and learning effect in offline learning environments is sparse. In order to solve this problem, this study designed an emotion observation experiment based on the offline learning environment, obtained the type of learner facial emotion and learning effect of 127 college students, and further explored the relationship between the two. The results show that: 1) We obtained eight types of learner emotion through the combined description method: joy, relaxation, surprise, meekness, contempt, disgust, sadness, anxiety and their respective PAD emotional mean. 2) We obtained the correlation results of the six emotions of joy, relaxation, surprise, meekness, contempt, and anxiety with the learning effect and the predicted value of the learning effect. 3) We then constructed an explanatory model of learner emotion and learning effect based on the offline learning environment.