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Background: Breast cancer (BC) is one of the most common malignancies worldwide, and its development is affected in various ways by the tumor microenvironment (TME). Tumor-derived mesenchymal progenitor cells (MPCs), as the most important components of the TME, participate in the proliferation and metastasis of BC in several ways. In this study, we aimed to characterize the genes associated with tumor-derived MPCs and determine their effects on BC cells. Methods: Tumor-derived MPCs and normal breast tissue-derived mesenchymal stem cells (MSCs) were isolated from tissues specimens of patients with BC. We conducted culture and passage, phenotype identification, proliferation and migration detection, inflammatory factor release detection, and other experiments on isolated MPCs from tumors and MSCs from normal breast tissues. Three paired tumor-derived MPCs and normal breast tissue-derived MSCs were then subjected to transcriptome analysis to determine the expression profiles of the relevant genes, and quantitative real-time polymerase chain reaction (qRT-PCR) was used to further confirm gene expression. Subsequently, the overexpression plasmids were transfected into tumor-derived MPCs, and the expression of various inflammatory factors of tumor-derived MPCs and their proliferation were characterized with a cell viability test reagent (Cell Counting Kit 8). Subsequently, the transfected tumor-derived MPCs were cocultured with BC cells using a conditioned medium coculture method to clarify the role of tumor-derived MSCs in BC. Results: Tumor-derived MPCs expressed stem cell characteristics including CD105, CD90, and CD73 and exhibited adipogenic and osteogenic differentiation in vitro. The proliferation of tumor-derived MPCs was significantly lower than that of normal breast tissue-derived MSCs, and the invasive metastatic ability was comparable; however, MPCs were found to release inflammatory factors such as interleukin 6 (IL-6) and transforming growth factor ß (TGF-ß). Transcriptome analysis showed that stomatin (STOM), collagen and calcium binding EGF domains 1 (CCBE1), and laminin subunit alpha 5 (LAMA5) were significantly upregulated in tumor-derived MPCs. Among them, STOM was highly expressed in tumor-derived MPCs, which mediated the slow proliferation of MPCs and promoted the proliferation of BC cells. Conclusions: STOM, CCBE1, and LAMA5 were highly expressed in tumor-derived MPCs, with STOM being found to retard the proliferation of MPCs but promote the proliferation of BC cells. There findings present new possibilities in targeted microenvironmental therapy for BC.
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The relationship between non-alcoholic fatty liver disease (NAFLD) and triple-negative breast cancer (TNBC) has been widely recognized, but the underlying mechanisms are still unknown. The objective of this study was to identify the hub genes associated with NAFLD and TNBC, and to explore the potential co-pathogenesis and prognostic linkage of these two diseases. We used GEO, TCGA, STRING, ssGSEA, and Rstudio to investigate the common differentially expressed genes (DEGs), conduct functional and signaling pathway enrichment analyses, and determine prognostic value between TNBC and NAFLD. GO and KEGG enrichment analyses of the common DEGs showed that they were enriched in leukocyte aggregation, migration and adhesion, apoptosis regulation, and the PPAR signaling pathway. Fourteen candidate hub genes most likely to mediate NAFLD and TNBC occurrence were identified and validation results in a new cohort showed that ITGB2, RAC2, ITGAM, and CYBA were upregulated in both diseases. A univariate Cox analysis suggested that high expression levels of ITGB2, RAC2, ITGAM, and CXCL10 were associated with a good prognosis in TNBC. Immune infiltration analysis of TNBC samples showed that NCF2, ICAM1, and CXCL10 were significantly associated with activated CD8 T cells and activated CD4 T cells. NCF2, CXCL10, and CYBB were correlated with regulatory T cells and myeloid-derived suppressor cells. This study demonstrated that the redox reactions regulated by the NADPH oxidase (NOX) subunit genes and the transport and activation of immune cells regulated by integrins may play a central role in the co-occurrence trend of NAFLD and TNBC. Additionally, ITGB2, RAC2, and ITGAM were upregulated in both diseases and were prognostic protective factors of TNBC; they may be potential therapeutic targets for treatment of TNBC patients with NAFLD, but further experimental studies are still needed.
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Background: Cone-beam breast computed tomography (CBBCT) is a new breast imaging technique, however, CBBCT is not yet widely used, and its future application will depend on its diagnostic potential and application value. Therefore, it is of great clinical significance to systematically review and analyze the diagnostic accuracy of CBBCT for breast cancer detection in existing studies and compare it with other traditional imaging methods for the diagnosis of breast lesions. Methods: We searched PubMed, Embase, Web of Science, and Chinese databases until August 2022 for relevant papers. Studies evaluating the diagnostic accuracy of CBBCT in women with suspected breast cancer were included. Each study's quality was evaluated using the Quality Assessment of Diagnostic Performance Studies-2 (QUADAS-2) instrument. Results: Eighteen studies with a total of 1,792 patients were included in the analysis. The overall pooled sensitivity and specificity of CBBCT in diagnosing breast cancer were 0.95 [95% confidence interval (CI): 0.91-0.97] and 0.72 (95% CI: 0.62-0.80), respectively. The area under the curve (AUC) for CBBCT was 0.92 (95% CI: 0.90-0.94). In a head-to-head comparison of CBBCT and digital mammography (DM), eight trials with 992 patients were included in the study, and the AUCs for CBBCT and DM were 0.94 (95% CI: 0.92-0.96) and 0.83 (95% CI: 0.80-0.83), respectively. In a head-to-head comparison of CBBCT and magnetic resonance imaging (MRI), four trials with 203 patients were included in the analysis; the AUC for CBBCT and MRI were 0.88 (95% CI: 0.85-0.91) and 0.96 (95% CI: 0.94-0.97), respectively. Conclusions: This meta-analysis of CBBCT test accuracy indicated encouraging diagnostic performance. In the summary of head-to-head comparative studies, there is a tendency for CBBCT to have greater diagnostic accuracy than DM, although its diagnostic performance is marginally inferior to that of MRI. However, the meta-analysis results were derived from studies with limited sample sizes. There is a need for more extensive research in this setting.