■先前已经报道了在基底样乳腺癌(BLBC)中SRY-box转录因子10(SOX10)表达的诊断实用性。然而,SOX10对BLBC细胞恶性程度的影响及潜在的分子机制仍未阐明.这里,我们研究了SOX10在BLBC进展中的调控机制和作用。
■从癌症基因组图谱数据库中提取BLBC患者的测序数据,以确定乳腺癌亚型中SOX10的转录组水平。随后,研究了SOX10在BLBC中的生物信息学相关性。免疫组织化学检测用于证实SOX10在临床病理标本(人乳腺癌石蜡组织)中的蛋白表达。RNA干扰用于下调SOX10表达,并使用定量PCR评估干扰效率。通过蛋白质印迹法测定与上皮-间质转化(EMT)途径相关的分子的表达水平。各种化验,比如Transwell,菌落形成,和流式细胞凋亡测定,进行评估BLBC细胞(MDA-MB-231)的恶性程度。
■生物信息学分析揭示了SOX10在各种乳腺癌亚型中的差异表达。在BLBC中观察到SOX10和免疫检查点表达之间的关联。此外,免疫相关分析表明,SOX10表达与效应免疫细胞呈正相关。SOX10被鉴定为潜在的免疫治疗靶标。与非基底样乳腺癌(N-BLBC)和乳腺腺病并列,免疫组织化学分析显示SOX10在BLBC中的表达上调,表明其潜在的诊断意义。单基因功能富集分析表明SOX10与EMT和肿瘤炎症指数相关。细胞分析的实验结果表明,SOX10的下调抑制了MDA-MB-231细胞中多种恶性肿瘤相关行为,特别影响EMT流程,迁移,入侵,扩散,克隆形成,和抗凋亡活性。
■我们得出结论,SOX10通过调节EMT途径促进BLBC细胞的恶性化。此外,我们观察到SOX10表达与免疫反应之间存在显著的相关性,表明SOX10在免疫治疗中的潜在意义。
UNASSIGNED: The diagnostic utility of SRY-box transcription factor 10 (SOX10) expression in basal-like breast cancer (BLBC) has been reported previously. However, the effect of SOX10 on the malignancy of BLBC cells and the underlying molecular mechanisms remain unelucidated. Here, we investigate the regulatory mechanisms and roles of
SOX10 in BLBC progression.
UNASSIGNED: Sequencing data from patients with BLBC were extracted from the Cancer Genome Atlas database to determine the transcriptomic levels of SOX10 across breast cancer subtypes. Subsequently, the bioinformatics relevance of
SOX10 in BLBC was investigated. Immunohistochemical assays were used to corroborate the protein expression of SOX10 in clinicopathological specimens (human breast cancer paraffin tissues). RNA interference was used to downregulate SOX10 expression, and the efficiency of interference was evaluated using quantitative PCR. The expression levels of molecules related to the epithelial-mesenchymal transition (EMT) pathway were determined by western blotting. Various assays, such as transwell, colony formation, and flow apoptosis assays, were conducted to assess the malignancy of BLBC cells (MDA-MB-231).
UNASSIGNED: Bioinformatics analyses revealed the differential expression of SOX10 in various breast cancer subtypes. An association between
SOX10 and immune checkpoint expression was observed in BLBC. Additionally, immune correlation analysis indicated a positive relationship between SOX10 expression and effector immune cells.
SOX10 was identified as a potential immunotherapeutic target. Juxtaposed with non-basal-like breast cancer (N-BLBC) and breast adenosis, immunohistochemical analysis revealed the upregulated expression of SOX10 in BLBC, indicating its potential diagnostic significance. Single-gene functional enrichment analysis indicated that SOX10 is associated with EMT and the tumor inflammatory index. Experimental outcomes from cellular assays suggested that the downregulation of SOX10 inhibited multiple malignancy-associated behaviors in MDA-MB-231 cells, specifically affecting the EMT process, migration, invasion, proliferation, clone formation, and anti-apoptotic activities.
UNASSIGNED: We concluded that SOX10 contributes to the malignancy of BLBC cells by modulating the EMT pathway. Moreover, we observed a notable correlation between SOX10 expression and immune responses, indicating the potential significance of
SOX10 in immunotherapy.