期刊
FRONTIERS IN GENETICS
卷 13, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fgene.2022.899419
关键词
gastric cancer; ferroptosis; long non-coding RNA; prognostic model; tumor microenvironment; immunotherapy
In this study, a novel prognostic model based on 10 ferroptosis-related lncRNA pairs was established. High-risk patients exhibited characteristics of high immune cell infiltration, upregulated carcinogenic and stromal activities, and heightened sensitivity to anti-tumor drugs. Low-risk patients showed better responses to methotrexate treatment and increased sensitivity to immunotherapy.
Background: The construction of ferroptosis-related lncRNA prognostic models in malignancies has been an intense area of research recently. However, most of the studies focused on the exact expression of lncRNAs and had limited application values. Herein, we aim to establish a novel prognostic model for gastric cancer (GC) patients and discuss its correlation with immune landscapes and treatment responses.Methods: The present study retrieved transcriptional data of GC patients from the Cancer Genome Atlas (TCGA) database. We identified differentially expressed ferroptosis-related lncRNAs between tumor and normal controls of GC samples. Based on a new method of cyclically single pairing, we constructed a 0 or 1 matrix of ferroptosis-related lncRNA pairs (FRLPs). A risk score signature consisting of 10 FRLPs was established using multi-step Cox regression analysis. Next, we performed a series of systematic analyses to investigate the association of the FRLP model and tumor microenvironment, biological function, and treatment responses. An alternative model to the FRLP risk score signature, the gene set score (GS) model was also constructed, which could represent the former when lncRNA expression was not available.Results: We established a novel prognostic signature of 10 ferroptosis-related lncRNA pairs. High-risk patients in our risk score model were characterized by high infiltration of immune cells, upregulated carcinogenic and stromal activities, and heightened sensitivity to a wide range of anti-tumor drugs, whereas low-risk patients were associated with better responses to methotrexate treatment and elevated immunotherapeutic sensitivity. The practicability of the FRLP risk score model was also validated in two independent microarray datasets downloaded from Gene Expression Omnibus (GEO) using the GS model. Finally, two online dynamic nomograms were built to enhance the clinical utility of the study.Conclusion: In this study, we developed a ferroptosis-related lncRNA pair-based risk score model that did not rely on the exact lncRNA expression level. This novel model might provide insights for the accurate prediction and comprehensive management for GC patients.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据