CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：m6A-Related lncRNA Signature Is Involved in Immunosuppression and Predicts the Patient Prognosis of the Age-Associated Ovarian Cancer.
m6A-Related lncRNA Signature Is Involved in Immunosuppression and Predicts the Patient Prognosis of the Age-Associated Ovarian Cancer.
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本研究构建了一个稳健的预测模型，用于预后管理，并揭示了 m6A 与免疫抑制之间的相互作用。此外，m6A lncRNA 特征可以预测化疗药物反应。这些将有助于新型治疗策略的开发，并为卵巢癌患者带来生存获益。
上皮性卵巢癌是一种与年龄相关的疾病，通常在晚期才被诊断出来。lncRNA已被发现与N6-甲基腺苷（m6A）相互作用，协同促进癌症进展并恶化患者预后。本研究旨在探讨m6A相关lncRNA特征在卵巢癌中的作用和机制。
我们检索了TCGA和CGGA测序数据，以识别m6A相关lncRNA特征，并使用LASSO算法构建了m6A评分（MS）。随后建立了临床列线图以预测患者的总生存期。接着进行GSEA分析以获得涉及的通路。分析了HLA基因表达、28种TIL（肿瘤浸润淋巴细胞）浸润以及抗癌周期，以比较高MS组和低MS组之间的免疫差异。最后，计算了免疫检查点基因表达和化疗药物的IC 50，并运行CMap以识别潜在化合物及其相应机制。
我们鉴定了16个m6A相关lncRNA并构建了MS模型。高MS组显示预后不良。构建了由MS和年龄组成的临床列线图，并以高准确度预测了1年、3年和5年生存率。GSEA分析显示抗原加工和呈递通路下调。免疫细胞浸润分析表明，高MS与Treg细胞、巨噬细胞高浸润以及低Th1/Th2比率相关。此外，在高MS组中观察到免疫检查点基因NRP1、TNFSF9和VSIR的高表达。最后，高MS组还预测了长春瑞滨和伏立诺他的低IC 50。
Epithelial ovarian cancers are age-associated diseases, usually diagnosed at an advanced stage. lncRNA has been discovered to interplay with N6-methyladenosine (m6A), working in tandem to promote cancer progression and worsening patient outcomes. This study is aimed at investigating the roles and mechanism of m6A-related lncRNA signature on ovarian cancers.
We retrieved TCGA and CGGA sequencing data to identify m6A-related lncRNA signature and constructed an m6A score (MS) using the LASSO algorithm. A clinical nomogram was then established to predict the overall survival of patients. Subsequently, GSEA analyses were conducted to obtain pathways involved. Expression of HLA genes, 28 tumor-infiltrating lymphocyte infiltration, and anticancer cycle were analyzed the immunological differences between high-MS and low-MS groups. Finally, immune checkpoint gene expressions and IC 50 of chemotherapeutic drugs were calculated, and CMap was run to identify the potential compounds and their corresponding mechanisms.
We identified 16 m6A-related lncRNAs and constructed an MS model. The high-MS group showed a poor prognosis. A clinical nomogram consists of MS, and age was constructed and predicted the 1-, 3-, and 5-year survival with high accuracy. GSEA analyses presented downregulated antigen processing and presentation pathways. Immunocyte infiltrating analyses demonstrated that high-MS was associated with high infiltration of Treg cells, macrophages, and low Th1/Th2 rate. Also, high expression of immune checkpoint genes NRP1 , TNFSF9 , and VSIR was observed in the high-MS group. Finally, the high-MS group also predicted low IC 50 of vinorelbine and vorinostat.
This study constructed a robust prediction model for prognostic management and revealed the cross-talk between m6A and immunosuppression. Besides, the m6A lncRNA signature can predict the chemotherapeutic drug response. These will shed light on the development of novel therapeutic strategies and render survival benefits for ovarian patients.
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