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HECTD3在上皮性卵巢癌中的表达及对铂耐药的影响
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Abstract:
目的：探讨HECTD3基因在卵巢癌组织中的表达，对上皮性卵巢癌铂耐药现象的影响及预后价值。方法：采用免疫组化法检测我院上皮性卵巢癌组织中HECTD3蛋白的表达情况，比较HECTD3蛋白表达与患者临床病理特征之间的相关性，利用HPA、GEPIA2和Kaplan-Meier Plotter数据库分别分析HECTD3蛋白在卵巢癌组织中的表达和预后价值；GSEA和CIBERSORT算法分别分析HECTD3高低表达组主要富集通路和HECTD3表达卵巢癌中主要免疫细胞的免疫浸润关系。结果：HECTD3蛋白在上皮性卵巢癌组织中高表达，且其高表达与卵巢癌的复发，尤其是铂耐药复发相关。Kaplan-Meier Plotter预后分析提示HECTD3基因高表达的患者预后更差(P < 0.05)。富集分析结果显示，HECTD3高低组差异基因主要富集在雌激素信号转导途径、IL6/JAK/STAT3信号通路等。CIBERSORT算法分析发现HECTD3基因与肿瘤微环境中中性粒细胞、CD4+记忆静息T细胞的浸润程度呈正相关(P < 0.05)。结论：在卵巢癌组织中，HECTD3蛋白的表达显著上调，它或许通过调控IL-6/JAK/STAT3信号通路以及影响肿瘤微环境中免疫细胞的浸润，进而加剧卵巢癌患者的铂类药物耐药复发，最终对患者的预后产生不利影响。
Objective: To investigate the expression of HECTD3 gene in ovarian cancer, its impact on the development of platinum resistance, and its prognostic significance. Methods: Immunohistochemistry was employed to examine the expression of HECTD3 protein in epithelial ovarian cancer tissues obtained from our hospital. The association between HECTD3 protein expression and patients’ clinical pathological features was evaluated. Additionally, we utilized the HPA, GEPIA2, and Kaplan-Meier Plotter databases to analyze the expression levels and prognostic significance of HECTD3 protein in ovarian cancer tissues. Furthermore, GSEA analysis was conducted to identify the key pathways enriched in HECTD3 high and low expression groups, while the CIBERSORT algorithm was applied to investigate the relationship between HECTD3 expression and immune cell infiltration in ovarian cancer. Results: HECTD3 was highly expressed in epithelial ovarian cancer, with elevated expression associated with recurrence, particularly platinum-resistant recurrence. Kaplan-Meier analysis indicated that patients with high HECTD3 expression had poorer prognosis (P < 0.05). Enrichment analysis revealed that differentially expressed genes in HECTD3 were primarily involved in estrogen signaling and IL6/JAK/STAT3 pathways. CIBERSORT analysis demonstrated a positive correlation between HECTD3 expression and the infiltration of neutrophils and CD4+ memory resting T cells in the tumor microenvironment (P < 0.05). Conclusion: HECTD3 protein is significantly upregulated in ovarian cancer tissue, potentially exacerbating platinum resistance through modulation of the IL-6/JAK/STAT3 signaling pathway and influencing immune cell infiltration in the tumor microenvironment, ultimately adversely affecting patient prognosis.
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