Integrated analysis of ferroptosis-related gene signature for overall survival prediction in Asian patients with hepatocellular carcinoma
Integrated analysis of ferroptosis-related gene signature for overall survival prediction in Asian patients with hepatocellular carcinoma
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DOI：
10.1007/s12094-022-02977-7
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发表时间：
2022-11-01
影响因子：
3.4
通讯作者：
Song，Wuqi
中科院分区：
文献类型：
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作者：
Wang，Zihang;Zhang，Lan;Song，Wuqi
肝细胞癌（Hepatocellular carcinoma，HCC）是亚洲最常见的恶性肿瘤之一.越来越多的证据表明，铁凋亡是一种非凋亡形式的细胞死亡，并发挥了重要作用，在癌症biology.MethodsBased上手动策划的铁凋亡相关基因集和TCGA-LIHC数据集的亚洲患者，我们使用DESeq 2，Kaplan-Meier分析，单变量考克斯回归，以确定差异表达的铁凋亡相关基因具有显着的预后能力。基于所选基因构建了风险特征，用于预测亚洲HCC患者的生存率。生存预测的准确性通过时间依赖的受试者工作特征（ROC）曲线分析证实。基因集变异分析（GSVA）被用来探索的签名的功能协会。应用铁凋亡电位指数（FPI）和xCell算法分别定量铁凋亡和免疫细胞浸润。两个独立的数据集从GEO和ICGC数据库被用于外部validation.ResultsThe铁中毒相关的签名可以准确地预测肝癌患者的生存结果在亚洲（P值< 0.0001）。我们发现，签名是一个独立的因素，有利于提高目前的临床病理特征，如甲胎蛋白（AFP）和残留肿瘤分类的量的风险分层。功能表征表明，肿瘤发生中的关键过程属于高风险组，例如炎症反应，这可能是HCC的主要驱动因素。高危组FPI、巨噬细胞和辅助性T细胞浸润均高于低危组。此外，两个独立的队列证实了我们的signature.ConclusionOverall的预后价值，我们的研究结果表明，潜在的应用ferroptosis相关基因作为独立的生物标志物在亚洲肝癌患者。靶向铁凋亡可能在临床上有用，超出已知的临床病理因素，并提供免疫治疗的好处。
PurposeHepatocellular carcinoma (HCC) is one of the most prevalent types of cancers in Asia. Accumulating evidence suggests that ferroptosis is a non-apoptotic form of cell death, and has played an important role in cancer biology.MethodsBased on the manually curated ferroptosis-related gene set and TCGA-LIHC dataset of Asian patients, we used DESeq2, Kaplan–Meier analysis, and univariate Cox regression to identify differentially expressed ferroptosis-related genes with significantly prognostic capacity. A risk signature was constructed based on the selected genes for predicting the survival of HCC patients in Asia. The survival prediction accuracy was confirmed by the time-dependent receiver operating characteristic (ROC) curve analysis. Gene set variation analysis (GSVA) was used to explore the functional associations of the signature. Ferroptosis potential index (FPI) and xCell algorithm was applied to quantify ferroptosis and immune cell infiltration, respectively. Two independent datasets from the GEO and the ICGC database were used for external validation.ResultsThe ferroptosis-related signature could accurately predict the survival outcomes of HCC patients in Asian (pvalue < 0.0001). We showed that the signature was an independent factor and was beneficial in elevating risk stratification of current clinicopathologic features, such as the amount of alpha-fetoprotein (AFP) and residual tumor classification. Functional characterization showed that critical processes in tumorigenesis belonged to the high-risk groups, for example inflammatory response, which may be the main driver of HCC. The high-risk group had higher FPIs and infiltrations of macrophages and T-helper cells than the low-risk group. Furthermore, two independent cohorts confirmed the prognostic value of our signature.ConclusionOverall, our results demonstrated potential application of ferroptosis-related genes as independent biomarkers in Asian HCC patients. Targeting ferroptosis may be clinically useful beyond known clinicopathological factors and provide benefit in immunotherapy.