Abstract：
BACKGROUND: Ovarian cancer (OC) is one of the malignant diseases of the reproductive system in elderly women. Aging-related genes (ARGs) were involved in tumor malignancy and cellular senescence, but the specifics of these mechanisms in OC remain unknown.
METHODS: ARGs expression and survival data of OC patients were collected from TCGA and CPTAC databases. Subtype classification was used to identify the roles of hub ARGs in OC progression, including function enrichment, immune infiltration, and drug sensitivity. LASSO regression was utilized to confirm the prognosis significance for these hub ARGs. MTT, EdU, Transwell, and wounding healing analysis confirmed the effect of IGFBP5 on the proliferation and migration ability of OC cells.
RESULTS: ARGs were ectopically expressed in OC tissues compared to normal ovary tissues. Three molecular subtypes were divided by ARGs for OC patients. There were significant differences in ferroptosis, m6A methylation, prognosis, immune infiltration, angiogenesis, differentiation level, and drug sensitivity among the three groups. LASSO regression indicated that 4 signatures, FOXO4, IGFBP5, OGG1 and TYMS, had important prognosis significance. Moreover, IGFBP5 was significantly correlated with immune infiltration. The hub ARG, IGFBP5, expression was significantly decreased in OC patients compared to normal women. IGFBP5 could also reduce the migration and proliferation ability of OC cells compared to vector and NC groups.
CONCLUSIONS: IGFBP5 was correlated with OC prognosis and associated with OC migration and proliferation. This gene may serve as potential prognostic biomarkers and therapeutic targets for OC patients.
METHODS: ARGs expression and survival data of OC patients were collected from TCGA and CPTAC databases. Subtype classification was used to identify the roles of hub ARGs in OC progression, including function enrichment, immune infiltration, and drug sensitivity. LASSO regression was utilized to confirm the prognosis significance for these hub ARGs. MTT, EdU, Transwell, and wounding healing analysis confirmed the effect of IGFBP5 on the proliferation and migration ability of OC cells.
RESULTS: ARGs were ectopically expressed in OC tissues compared to normal ovary tissues. Three molecular subtypes were divided by ARGs for OC patients. There were significant differences in ferroptosis, m6A methylation, prognosis, immune infiltration, angiogenesis, differentiation level, and drug sensitivity among the three groups. LASSO regression indicated that 4 signatures, FOXO4, IGFBP5, OGG1 and TYMS, had important prognosis significance. Moreover, IGFBP5 was significantly correlated with immune infiltration. The hub ARG, IGFBP5, expression was significantly decreased in OC patients compared to normal women. IGFBP5 could also reduce the migration and proliferation ability of OC cells compared to vector and NC groups.
CONCLUSIONS: IGFBP5 was correlated with OC prognosis and associated with OC migration and proliferation. This gene may serve as potential prognostic biomarkers and therapeutic targets for OC patients.
摘要：
背景：卵巢癌（OC）是老年女性生殖系统的恶性疾病之一。衰老相关基因(ARGs)参与肿瘤恶性程度和细胞衰老,但是OC中这些机制的具体细节仍然未知。
方法：从TCGA和CPTAC数据库收集OC患者的ARGs表达和生存数据。亚型分类用于确定中枢ARGs在OC进展中的作用，包括功能富集，免疫浸润，和药物敏感性。LASSO回归用于确认这些中心ARGs的预后意义。MTT,EdU,Transwell,创伤愈合分析证实了IGFBP5对OC细胞增殖和迁移能力的影响。
结果：与正常卵巢组织相比，ARGs在OC组织中异位表达。OC患者的三种分子亚型按ARGs进行划分。铁性有显著差异，m6A甲基化，预后,免疫浸润，血管生成,分化水平,三组的药物敏感性。LASSO回归表明有4个签名，FOXO4,IGFBP5,OGG1和TYMS,具有重要的预后意义。此外，IGFBP5与免疫浸润显著相关。枢纽ARG，IGFBP5，在OC患者中的表达较正常女性显著下降。与载体和NC组相比，IGFBP5还可以降低OC细胞的迁移和增殖能力。
结论：IGFBP5与OC预后相关，与OC迁移和增殖相关。该基因可作为OC患者的潜在预后生物标志物和治疗靶标。
方法：从TCGA和CPTAC数据库收集OC患者的ARGs表达和生存数据。亚型分类用于确定中枢ARGs在OC进展中的作用，包括功能富集，免疫浸润，和药物敏感性。LASSO回归用于确认这些中心ARGs的预后意义。MTT,EdU,Transwell,创伤愈合分析证实了IGFBP5对OC细胞增殖和迁移能力的影响。
结果：与正常卵巢组织相比，ARGs在OC组织中异位表达。OC患者的三种分子亚型按ARGs进行划分。铁性有显著差异，m6A甲基化，预后,免疫浸润，血管生成,分化水平,三组的药物敏感性。LASSO回归表明有4个签名，FOXO4,IGFBP5,OGG1和TYMS,具有重要的预后意义。此外，IGFBP5与免疫浸润显著相关。枢纽ARG，IGFBP5，在OC患者中的表达较正常女性显著下降。与载体和NC组相比，IGFBP5还可以降低OC细胞的迁移和增殖能力。
结论：IGFBP5与OC预后相关，与OC迁移和增殖相关。该基因可作为OC患者的潜在预后生物标志物和治疗靶标。
