Department of Bone and Soft Tissue Tumors, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China.
Department of Hepatobiliary Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China.
Front Immunol. 2022 Jul 8;13:929089. doi: 10.3389/fimmu.2022.929089. eCollection 2022.
Hepatocellular carcinoma (HCC) with high heterogeneity is a common malignancy worldwide, but effective treatments are limited. Ferroptosis plays a critical role in tumors as a novel iron-dependent and reactive oxygen species-reliant type of cell death. Several studies have shown that long non-coding RNAs (lncRNAs) can drive HCC initiation and progression. However, the prognostic value of ferroptosis-related lncRNAs in patients with HCC has not been explored comprehensively. Gene set variation analysis (GSVA) based on gene set and RNA-seq profiles obtained from public databases indicated that ferroptosis is suppressed in HCC patients. Ferroptosis-related differentially expressed lncRNAs were screened by Pearson's test. Univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression, and multivariate Cox regression were performed to establish a novel five ferroptosis-related lncRNA signature in the training cohort with 60% patients, which was further verified in the testing cohort with 40% patients. Dimensionality reduction analysis, Kaplan-Meier curve, receiver operating characteristic (ROC) curve, independent prognostic analysis, and stratification analysis confirmed that our signature had a high clinical application value in predicting the overall survival of HCC patients. Compared to the clinicopathological factors and the other four published HCC prognostic signatures, the current risk model had a better predictive value. The comparison results of functional enrichment, tumor immune microenvironment, genomic heterogeneity, and drug sensitivity between the high- and low-risk groups showed that the risk score is associated with extensive genomic alterations, immunosuppressive tumor microenvironment, and clinical treatment response. Finally, cell experiments showed that silencing LNCSRLR expression inhibited the growth, proliferation, migration, and invasion of the HCC cell line. Thus, the model can function as an efficient indicator for predicting clinical prognosis and treatment of anticancer drugs in HCC patients.
肝细胞癌（HCC）具有高度异质性，是一种常见的恶性肿瘤，但有效的治疗方法有限。铁死亡作为一种新型的铁依赖性和活性氧依赖性细胞死亡方式，在肿瘤中起着关键作用。一些研究表明，长链非编码 RNA（lncRNA）可以驱动 HCC 的发生和发展。然而，铁死亡相关 lncRNA 在 HCC 患者中的预后价值尚未得到全面探讨。基于公共数据库中基因集和 RNA-seq 谱获得的基因集变异分析（GSVA）表明，HCC 患者的铁死亡受到抑制。通过 Pearson 检验筛选铁死亡相关差异表达的 lncRNA。在 60%的患者的训练队列中进行单因素 Cox 回归、最小绝对收缩和选择算子（LASSO）回归以及多因素 Cox 回归，以建立一个新的五铁死亡相关 lncRNA 特征，然后在 40%的患者的测试队列中进行验证。降维分析、Kaplan-Meier 曲线、受试者工作特征（ROC）曲线、独立预后分析和分层分析证实，该特征在预测 HCC 患者的总生存率方面具有较高的临床应用价值。与临床病理因素和其他四个已发表的 HCC 预后特征相比，该风险模型具有更好的预测价值。高低风险组间功能富集、肿瘤免疫微环境、基因组异质性和药物敏感性的比较结果表明，风险评分与广泛的基因组改变、免疫抑制性肿瘤微环境和临床治疗反应相关。最后，细胞实验表明，沉默 LNCSRLR 表达抑制了 HCC 细胞系的生长、增殖、迁移和侵袭。因此，该模型可以作为预测 HCC 患者临床预后和抗癌药物治疗的有效指标。
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