一个新型与 8 基因组不稳定性相关的 lncRNAs 特征可预测胃癌的预后和药物敏感性。

A novel 8-genome instability-associated lncRNAs signature predicting prognosis and drug sensitivity in gastric cancer.

机构信息

Department of Interventional, Cancer Hospital of Shantou University Medical College, Shantou, China.

Department of Nuclear Medicine, The First People's Hospital of Jingzhou, The First Affiliated Hospital of Yangtze University, Jingzhou, Hubei, China.

出版信息

Int J Immunopathol Pharmacol. 2022 Jan-Dec;36:3946320221103195. doi: 10.1177/03946320221103195.

DOI:10.1177/03946320221103195

PMID:35696730

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9203952/

Abstract

BACKGROUND

Genome instability lncRNA (GILnc) is prevalently related with gastric cancer (GC) pathophysiology. However, the study on the relationship GILnc and prognosis and drug sensitivity of GC remains scarce.

METHOD

We extracted expression data of 375 GC patients from TCGA cohort and 205 GC patients from GSE26942 cohort. Then, lncRNA was separated from expression data, and systematically characterized the 8 marker lncRNAs using the LASSO method. Next, we constructed a GILnc model (GILnc score) to quantify the GILnc index of each GC patient. Finally, we analyzed the relationship between GILnc score and clinical traits including survival outcomes, TP53, and drug sensitivity of GC.

RESULTS

Based on a computational frame, 205 GILncs in GC has been identified. Then, a 8 GILncs was successfully established to predict overall survival in GC patients based on LASSO analysis, divided GC samples into high GILnc score and low GILnc score groups with significantly different outcome and was validated in multiple independent patient cohorts. Furthermore, GILnc model is better than the prediction performance of two recently published lncRNA signatures, and the high GILnc score group was more sensitive to mitomycin. Besides, the GILnc score has greater prognostic significance than TP53 mutation status alone and is capable of identifying intermediate subtype group existing with partial TP53 functionality in TP53 wild-type patients. Finally, GILnc signature as verified in GSE26942.

CONCLUSION

We applied bioinformatics approaches to suggest that a 8 GILnc signature could serve as prognostic biomarkers, and provide a novel direction to explore the pathogenesis of GC.

摘要

背景

基因组不稳定 lncRNA（GILnc）与胃癌（GC）的病理生理学密切相关。然而，关于 GILnc 与 GC 预后和药物敏感性的关系的研究仍然很少。

方法

我们从 TCGA 队列中提取了 375 名 GC 患者的表达数据，从 GSE26942 队列中提取了 205 名 GC 患者的表达数据。然后，从表达数据中分离出 lncRNA，使用 LASSO 方法系统地对 8 个标记 lncRNA 进行特征化。接下来，我们构建了一个 GILnc 模型（GILnc 评分），以量化每个 GC 患者的 GILnc 指数。最后，我们分析了 GILnc 评分与临床特征之间的关系，包括生存结果、TP53 和 GC 的药物敏感性。

结果

基于一个计算框架，已经确定了 205 个 GC 中的 GILncs。然后，通过 LASSO 分析成功建立了一个 8 个 GILncs 的模型来预测 GC 患者的总生存率，将 GC 样本分为高 GILnc 评分和低 GILnc 评分组，两组之间的预后有显著差异，并在多个独立的患者队列中得到验证。此外，GILnc 模型的预测性能优于最近发表的两个 lncRNA 特征，高 GILnc 评分组对丝裂霉素更敏感。此外，GILnc 评分比 TP53 突变状态本身具有更大的预后意义，并且能够在 TP53 野生型患者中识别出具有部分 TP53 功能的中间亚型组。最后，在 GSE26942 中验证了 GILnc 特征。