Department of Assisted Reproductive Centre, Zhuzhou Central Hospital, Xiangya Hospital Zhuzhou Central South University, Central South University, Zhuzhou, Hunan, China.
Department of Obstetrics and Gynecology, Zhuzhou Central Hospital, Xiangya Hospital Zhuzhou Central South University, Central South University, Zhuzhou, Hunan, China.
Curr Cancer Drug Targets. 2024;24(7):760-778. doi: 10.2174/0115680096276852231113111412.
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.
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.
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.
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.
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）参与肿瘤恶性和细胞衰老，但这些机制在 OC 中的具体情况尚不清楚。
从 TCGA 和 CPTAC 数据库中收集 OC 患者的 ARGs 表达和生存数据。亚类分类用于确定 OC 进展中这些关键 ARGs 的作用，包括功能富集、免疫浸润和药物敏感性。LASSO 回归用于确认这些关键 ARGs 的预后意义。MTT、EdU、Transwell 和划痕愈合分析证实了 IGFBP5 对 OC 细胞增殖和迁移能力的影响。
ARGs 在 OC 组织中的表达高于正常卵巢组织。根据 ARGs 将 OC 患者分为三个分子亚型。三组间铁死亡、m6A 甲基化、预后、免疫浸润、血管生成、分化水平和药物敏感性存在显著差异。LASSO 回归表明，FOXO4、IGFBP5、OGG1 和 TYMS 这 4 个特征具有重要的预后意义。此外，IGFBP5 与免疫浸润显著相关。与正常女性相比，OC 患者的关键 ARG IGFBP5 表达明显降低。IGFBP5 还可以降低 OC 细胞的迁移和增殖能力，与载体和 NC 组相比。
IGFBP5 与 OC 预后相关，并与 OC 迁移和增殖相关。该基因可能成为 OC 患者潜在的预后生物标志物和治疗靶点。
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