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m6A 相关靶点的基因特征可预测卵巢癌的预后和免疫治疗反应。

Gene signature of m6A-related targets to predict prognosis and immunotherapy response in ovarian cancer.

机构信息

Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, 430060, China.

Department of Obstetrics and Gynecology Ultrasound, Renmin Hospital of Wuhan University, Wuhan, 430060, China.

出版信息

J Cancer Res Clin Oncol. 2023 Feb;149(2):593-608. doi: 10.1007/s00432-022-04162-3. Epub 2022 Sep 1.

Abstract

PURPOSE

The aim of the study was to construct a risk score model based on m6A-related targets to predict overall survival and immunotherapy response in ovarian cancer.

METHODS

The gene expression profiles of 24 m6A regulators were extracted. Survival analysis screened 9 prognostic m6A regulators. Next, consensus clustering analysis was applied to identify clusters of ovarian cancer patients. Furthermore, 47 phenotype-related differentially expressed genes, strongly correlated with 9 prognostic m6A regulators, were screened and subjected to univariate and the least absolute shrinkage and selection operator (LASSO) Cox regression. Ultimately, a nomogram was constructed which presented a strong ability to predict overall survival in ovarian cancer.

RESULTS

CBLL1, FTO, HNRNPC, METTL3, METTL14, WTAP, ZC3H13, RBM15B and YTHDC2 were associated with worse overall survival (OS) in ovarian cancer. Three m6A clusters were identified, which were highly consistent with the three immune phenotypes. What is more, a risk model based on seven m6A-related targets was constructed with distinct prognosis. In addition, the low-risk group is the best candidate population for immunotherapy.

CONCLUSION

We comprehensively analyzed the m6A modification landscape of ovarian cancer and detected seven m6A-related targets as an independent prognostic biomarker for predicting survival. Furthermore, we divided patients into high- and low-risk groups with distinct prognosis and select the optimum population which may benefit from immunotherapy and constructed a nomogram to precisely predict ovarian cancer patients' survival time and visualize the prediction results.

摘要

目的

本研究旨在构建基于 m6A 相关靶点的风险评分模型,以预测卵巢癌的总生存期和免疫治疗反应。

方法

提取了 24 个 m6A 调节因子的基因表达谱。生存分析筛选出 9 个预后 m6A 调节因子。接下来,采用共识聚类分析对卵巢癌患者进行聚类。此外,筛选出与 9 个预后 m6A 调节因子强相关的 47 个表型相关差异表达基因,并进行单变量和最小绝对收缩和选择算子(LASSO)Cox 回归分析。最终构建了一个列线图,该列线图具有较强的预测卵巢癌总生存期的能力。

结果

CBLL1、FTO、HNRNPC、METTL3、METTL14、WTAP、ZC3H13、RBM15B 和 YTHDC2 与卵巢癌的总生存期(OS)较差相关。鉴定出 3 个 m6A 聚类,它们与 3 种免疫表型高度一致。此外,基于 7 个 m6A 相关靶点构建了一个风险模型,具有明显的预后。此外,低风险组是免疫治疗的最佳候选人群。

结论

我们全面分析了卵巢癌的 m6A 修饰图谱,并检测到 7 个 m6A 相关靶点作为预测生存的独立预后生物标志物。此外,我们将患者分为具有明显预后的高风险组和低风险组,并选择最适合可能受益于免疫治疗的人群,并构建列线图以精确预测卵巢癌患者的生存时间并可视化预测结果。

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