Geng Wei, Lv Zhilei, Fan Jinshuo, Xu Juanjuan, Mao Kaimin, Yin Zhengrong, Qing Wanlu, Jin Yang
NHC Key Laboratory of Pulmonary Diseases, Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
Front Cell Dev Biol. 2021 Mar 29;9:657667. doi: 10.3389/fcell.2021.657667. eCollection 2021.
Lung adenocarcinoma (LUAD) is a highly heterogeneous tumor with substantial somatic mutations and genome instability, which are emerging hallmarks of cancer. Long non-coding RNAs (lncRNAs) are promising cancer biomarkers that are reportedly involved in genomic instability. However, the identification of genome instability-related lncRNAs (GInLncRNAs) and their clinical significance has not been investigated in LUAD. We determined GInLncRNAs by combining somatic mutation and transcriptome data of 457 patients with LUAD and probed their potential function using co-expression network and Gene Ontology (GO) enrichment analyses. We then filtered GInLncRNAs by Cox regression and LASSO regression to construct a genome instability-related lncRNA signature (GInLncSig). We subsequently evaluated GInLncSig using correlation analyses with mutations, external validation, model comparisons, independent prognostic significance analyses, and clinical stratification analyses. Finally, we established a nomogram for prognosis prediction in patients with LUAD and validated it in the testing set and the entire TCGA dataset. We identified 161 GInLncRNAs, of which seven were screened to develop a prognostic GInLncSig model (LINC01133, LINC01116, LINC01671, FAM83A-AS1, PLAC4, MIR223HG, and AL590226.1). GInLncSig independently predicted the overall survival of patients with LUAD and displayed an improved performance compared to other similar signatures. Furthermore, GInLncSig was related to somatic mutation patterns, suggesting its ability to reflect genome instability in LUAD. Finally, a nomogram comprising the GInLncSig and tumor stage exhibited improved robustness and clinical practicability for predicting patient prognosis. Our study identified a signature for prognostic prediction in LUAD comprising seven lncRNAs associated with genome instability, which may provide a useful indicator for clinical stratification management and treatment decisions for patients with LUAD.
肺腺癌（LUAD）是一种高度异质性肿瘤，具有大量体细胞突变和基因组不稳定性，这些都是癌症新出现的特征。长链非编码RNA（lncRNAs）是很有前景的癌症生物标志物，据报道其参与基因组不稳定性。然而，尚未在LUAD中研究与基因组不稳定性相关的lncRNAs（GInLncRNAs）及其临床意义。我们通过整合457例LUAD患者的体细胞突变和转录组数据来确定GInLncRNAs，并使用共表达网络和基因本体（GO）富集分析探究其潜在功能。然后，我们通过Cox回归和LASSO回归筛选GInLncRNAs，以构建与基因组不稳定性相关的lncRNA特征（GInLncSig）。随后，我们通过与突变的相关性分析、外部验证、模型比较、独立预后意义分析和临床分层分析来评估GInLncSig。最后，我们建立了一个用于LUAD患者预后预测的列线图，并在测试集和整个TCGA数据集中进行了验证。我们鉴定出161个GInLncRNAs，其中7个被筛选出来用于构建预后GInLncSig模型（LINC01133、LINC01116、LINC01671、FAM83A-AS1、PLAC4、MIR223HG和AL590226.1）。GInLncSig独立预测了LUAD患者的总生存期，并且与其他类似特征相比表现出更好的性能。此外，GInLncSig与体细胞突变模式相关，表明其能够反映LUAD中的基因组不稳定性。最后，一个包含GInLncSig和肿瘤分期的列线图在预测患者预后方面表现出更高的稳健性和临床实用性。我们的研究确定了一个用于LUAD预后预测的特征，该特征由7个与基因组不稳定性相关的lncRNAs组成，这可能为LUAD患者的临床分层管理和治疗决策提供有用的指标。
