UTRN as a potential biomarker in breast cancer: a comprehensive bioinformatics and in vitro study.

Utrophin (UTRN), known as a tumor suppressor, potentially regulates tumor development and the immune microenvironment. However, its impact on breast cancer's development and treatment remains unstudied. We conducted a thorough examination of UTRN using both bioinformatic and in vitro experiments in this study. We discovered UTRN expression decreased in breast cancer compared to standard samples. High UTRN expression correlated with better prognosis. Drug sensitivity tests and RT-qPCR assays revealed UTRN's pivotal role in tamoxifen resistance. Furthermore, the Kruskal-Wallis rank test indicated UTRN's potential as a valuable diagnostic biomarker for breast cancer and its utility in detecting T stage of breast cancer. Additionally, our results demonstrated UTRN's close association with immune cells, inhibitors, stimulators, receptors, and chemokines in breast cancer (BRCA). This research provides a novel perspective on UTRN's role in breast cancer's prognostic and therapeutic value. Low UTRN expression may contribute to tamoxifen resistance and a poor prognosis. Specifically, UTRN can improve clinical decision-making and raise the diagnosis accuracy of breast cancer.

MED16 Promotes Tumour Progression and Tamoxifen Sensitivity by Modulating Autophagy through the mTOR Signalling Pathway in ER-Positive Breast Cancer.

Recent studies have shown that the mediator complex (MED) plays a vital role in tumorigenesis and development, but the role of MED16 (mediator complex subunit 16) in breast cancer (BC) is not clear. Increasing evidence has shown that the mTOR pathway is important for tumour progression and therapy. In this study, we demonstrated that the mTOR signalling pathway is regulated by the expression level of MED16 in ER+ breast cancer. With the analysis of bioinformatics data and clinical specimens, we revealed an elevated expression of MED16 in luminal subtype tumours. We found that MED16 knockdown significantly inhibited cell proliferation and promoted G1 phase cell cycle arrest in ER+ BC cell lines. Downregulation of MED16 markedly reduced the sensitivity of ER+ BC cells to tamoxifen and increased the stemness and autophagy of ER+ BC cells. Bioinformatic analysis of similar genes to MED16 were mainly enriched in autophagy, endocrine therapy and mTOR signalling pathways, and the inhibition of mTOR-mediated autophagy restored sensitivity to tamoxifen by MED16 downregulation in ER+ BC cells. These results suggest an important role of MED16 in the regulation of tamoxifen sensitivity in ER+ BC cells, crosstalk between the mTOR signalling pathway-induced autophagy, and together, with the exploration of tamoxifen resistance, may indicate a new therapy option for endocrine therapy-resistant patients.

Cell Division Cycle-Associated Protein 3 (CDCA3) Is a Potential Biomarker for Clinical Prognosis and Immunotherapy in Pan-Cancer.

CDCA3 is an essential regulator in cell mitosis and can regulate many physiological and pathological processes in the human body by stimulating certain proteins such as cell cycle regulatory proteins, transcription factors, and signal transduction molecules. Although several studies have shown that dysregulation of CDCA3 is a common phenomenon in human cancers, no systematic pan-cancer analysis has been performed. In this study, we comprehensively investigated the role of CDCA3 in 33 human cancer types by utilizing multiple cancer-related databases and bioinformatics analysis tools, including TCGA, GTEx, GEPIA, TIMER, STRING, Metascape, and Cytoscape. Evidence from bioinformatics databases shows that CDCA3 is overexpressed in almost all human cancer types, and its overexpression is significantly associated with survival in patients with more than ten cancer types. CDCA3 expression positively correlates with immune cell infiltration levels in multiple human cancer types. Furthermore, the results of the GSEA analysis revealed that overexpression of CDCA3 may promote the malignant progression of cancer by activating various oncogenic signaling pathways in human cancers. In conclusion, our pan-cancer analysis provides a comprehensive overview of the oncogenic role of CDCA3 in multiple human cancer types, suggesting that CDCA3 may serve as a potential therapeutic target and prognostic biomarker in multiple human cancer types.

Comprehensive Analysis of Necroptosis-Related Genes as Prognostic Factors and Immunological Biomarkers in Breast Cancer.

Breast cancer (BC) is a lethal malignancy with a poor prognosis. Necroptosis is critical in the progression of cancer. However, the expression of genes involved in necroptosis in BC and their association with prognosis remain unclear. We investigated the predictive potential of necroptosis-related genes in BC samples from the TCGA dataset. We used LASSO regression to build a risk model consisting of twelve necroptosis-related genes in BC. Using the necroptosis-related risk model, we were able to successfully classify BC patients into high- and low-risk groups with significant prognostic differences (p = 4.872 × 10 -7). Additionally, we developed a matched nomogram predicting 5, 7, and 10-year overall survival in BC patients based on this necroptosis-related risk model. Our next step was to perform multiple GSEA analyses to explore the biological pathways through which these necroptosis-related risk genes influence cancer progression. For these twelve risk model genes, we analyzed CNV, SNV, OS, methylation, immune cell infiltration, and drug sensitivity in pan-cancer. In addition, immunohistochemical data from the THPA database were used to validate the protein expression of these risk model genes in BC. Taken together, we believe that necroptosis-related genes are considered potential therapeutic targets in BC and should be further investigated.