Liu Jun-Yan, Yao Jing, Liu Jia-Jia, He Tao, Wang Fang-Jie, Xie Tian-Yu, Cui Jian-Xin, Yang Xiao-Dong
Department of General Surgery, The First Medical Center, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.
Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
Front Oncol. 2022 Sep 29;12:1020255. doi: 10.3389/fonc.2022.1020255. eCollection 2022.
Gastric cancer (GC), a malignant tumor of digestive tract, is characterized by a high death rate. Thus, it is of particular importance to clarify the mechanisms of GC and gain new molecular targets for the sake of preventing and treating GC. It was reported that long non-coding RNAs (IncRNAs) are prognostic factors to cancer. Ferroptosis refers to a process of programmed cell death dependent on iron. This study sets out to investigate the expression and function of ferroptosis-related lncRNA (FRlncRNA) in GC. TCGA datasets offered RNA-seq data for 375 GC patients and clinical data for 443 GC patients. Based on Pearson's correlation analysis, we studied their expression and identified the FRlncRNAs. Differentially expressed prognosis related to FRlncRNA were determined with the help of the Wilcoxon test and univariate Cox regression analysis. To evaluate the accuracy of the prognostic capacity, researchers used the Kaplan-Meier technique, as well as univariate and multivariate Cox regression and receiver operating characteristic (ROC) curve studies. We also carried out the real-time PCR and CCK8 assays to examine the expression and function of FRlncRNA. In this study, we identified 50 ferroptosis-related DEGs which were involved in tumor progression. In addition, we identified 33 survival-related FRlncRNAs. Among them, lncRNA associated with SART3 regulation of splicing(LASTR) was confirmed to be highly expressed in GC specimens compared to non-tumor specimens in this cohort. Survival assays illuminated that the high LASTR expression predicted a shorter overall survival and progression-free survival of GC patients. Based on multivariate Cox regression analyses, it was confirmed that the GC had a worse chance of surviving the disease overall if their tumors expressed LASTR, which was an independent prognostic indication. Then, Loss-of-function tests showed that knocking down LASTR had a significant effect on reducing the proliferation of GC cells. Finally, we found that the expression of LASTR was negatively associated with CD8 T cells, T cells, Th17 cells, and T helper cells. Overall, our findings identified a novel survival-related FRlncRNA, LASTR which possibly can serve as a novel prognostic biomarker predicting response to cancer immunotherapy and therapeutic target for GC patients.
胃癌（GC）是一种消化道恶性肿瘤，死亡率很高。因此，阐明胃癌的发病机制并找到新的分子靶点对于预防和治疗胃癌尤为重要。据报道，长链非编码RNA（lncRNAs）是癌症的预后因素。铁死亡是指一种依赖铁的程序性细胞死亡过程。本研究旨在探讨铁死亡相关lncRNA（FRlncRNA）在胃癌中的表达及功能。TCGA数据集提供了375例GC患者的RNA测序数据和443例GC患者的临床数据。基于Pearson相关性分析，我们研究了它们的表达并鉴定出FRlncRNAs。借助Wilcoxon检验和单因素Cox回归分析确定与FRlncRNA相关的差异表达预后。为了评估预后能力的准确性，研究人员使用了Kaplan-Meier技术以及单因素和多因素Cox回归分析和受试者工作特征（ROC）曲线研究。我们还进行了实时PCR和CCK8试验来检测FRlncRNA的表达和功能。在本研究中，我们鉴定出50个与铁死亡相关的差异表达基因（DEGs），它们参与肿瘤进展。此外，我们鉴定出33个与生存相关的FRlncRNAs。其中，与SART3剪接调控相关的lncRNA（LASTR）在该队列中被证实与非肿瘤标本相比在GC标本中高表达。生存分析表明，高LASTR表达预示着GC患者的总生存期和无进展生存期较短。基于多因素Cox回归分析，证实如果GC患者的肿瘤表达LASTR，其总体生存几率更差，这是一个独立的预后指标。然后，功能丧失试验表明敲低LASTR对降低GC细胞的增殖有显著影响。最后，我们发现LASTR的表达与CD8 T细胞、T细胞、Th17细胞和辅助性T细胞呈负相关。总体而言，我们的研究结果鉴定出一种新的与生存相关的FRlncRNA，LASTR，它可能作为一种新的预后生物标志物，预测癌症免疫治疗反应，并成为GC患者的治疗靶点。
