研究动态
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线粒体相关的长链非编码RNA签名预测卵巢癌的预后和药物反应。

Mitophagy-related long non-coding RNA signature predicts prognosis and drug response in Ovarian Cancer.

发表日期:2023 Aug 26
作者: Jiao Wang, Xiaocui Zhang, Fei Zheng, Qing Yang, Fangfang Bi
来源: Journal of Ovarian Research

摘要:

卵巢癌(OC)是女性生殖系统中预后最差的恶性肿瘤。线粒体自噬和长链非编码 RNA (lncRNA) 在肿瘤发生、发展和药物耐药性中起着关键作用。线粒体自噬相关的 lncRNA 在 OC 预后和治疗反应中的影响尚未阐明。我们从 The Cancer Genome Atlas 数据库获取了与 OC 相关的 RNA 序列、拷贝数变异、体细胞突变和临床病理信息,并从 Reactome 数据库获取了与线粒体自噬相关的基因集。使用 Pearson 相关分析鉴定了线粒体自噬相关的 lncRNA。运用 UniCox、LASSO 和向前逐步回归分析构建了预后 lncRNA 签名。风险得分高于或低于中位数的个体分别归类为高风险组或低风险组。使用 Kaplan-Meier 估计器、接受者操作特征曲线、决策曲线分析和 Cox 回归分析对风险模型进行了分析,并使用内部数据集进行了验证。对 LINC00174 在临床样本和 OC 细胞系中进行了验证。我们还回顾了有关 LINC00174 在癌症中的作用的报告。随后构建了一个 nomogram 模型。此外,利用 Genomics of Drug Sensitivity in Cancer 数据库探索了风险模型与抗肿瘤药物敏感性之间的关系。进行基因集变异分析以评估两组之间的生物学功能差异。最后,构建了与 lncRNA 预后签名相关的竞争性内源性 RNA (ceRNA) 网络。预后签名显示高风险组患者预后较差。图表模型展示了较高的准确性和预测潜力。LINC00174 主要作为癌基因发挥作用,并在 OC 中上调表达;其沉默抑制了 OC 细胞的增殖和迁移,并促进了细胞凋亡。高风险患者对顺铂和奥拉帕利比低风险患者的敏感性更低。ceRNA 网络有助于探索 lncRNA 的潜在调控机制。线粒体自噬相关的 lncRNA 签名可用于评估 OC 患者的生存和药物敏感性,ceRNA 网络可能为 OC 患者提供新的治疗靶点。© 2023. BioMed Central Ltd., part of Springer Nature.
Ovarian cancer (OC) is the most malignant tumor with the worst prognosis in female reproductive system. Mitophagy and long non-coding RNAs (lncRNAs) play pivotal roles in tumorigenesis, development, and drug resistance. The effects of mitophagy-related lncRNAs on OC prognosis and therapeutic response remain unelucidated.We retrieved OC-related RNA sequence, copy number variation, somatic mutation, and clinicopathological information from The Cancer Genome Atlas database and mitophagy-related gene sets from the Reactome database. Pearson's correlation analysis was used to distinguish mitophagy-related lncRNAs. A prognostic lncRNA signature was constructed using UniCox, LASSO, and forward stepwise regression analysis. Individuals with a risk score above or below the median were classified as high- or low-risk groups, respectively. The risk model was analyzed using the Kaplan-Meier estimator, receiver operating characteristic curve, decision curve analysis, and Cox regression analysis and validated using an internal dataset. LINC00174 was validated in clinical samples and OC cell lines. We also reviewed reports on the role of LINC00174 in cancer. Subsequently, a nomogram model was constructed. Furthermore, the Genomics of Drug Sensitivity in Cancer database was used to explore the relationship between the risk model and anti-tumor drug sensitivity. Gene set variation analysis was performed to assess potential differences in biological functions between the two groups. Finally, a lncRNA prognostic signature-related competing endogenous RNA (ceRNA) network was constructed.The prognostic signature showed that patients in the high-risk group had a poorer prognosis. The nomogram exhibited satisfactory accuracy and predictive potential. LINC00174 mainly acts as an oncogene in cancer and is upregulated in OC; its knockdown inhibited the proliferation and migration, and promoted apoptosis of OC cells. High-risk patients were more insensitive to cisplatin and olaparib than low-risk patients. The ceRNA network may help explore the potential regulatory mechanisms of lncRNAs.The mitophagy-related lncRNA signature can help estimate the survival and drug sensitivity, the ceRNA network may provide novel therapeutic targets for patients with OC.© 2023. BioMed Central Ltd., part of Springer Nature.