Genome-Wide Screening Identifies Prognostic Long Noncoding RNAs in Hepatocellular Carcinoma

Feng, Yujie; Hu, Xiao; Ma, Kai; Zhang, Bingyuan; Sun, Changfu

doi:10.1155/2021/6640652

Cited by 17 publications

(14 citation statements)

References 38 publications

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“…LncRNA NRAV has been reported to be involved in the antiviral immune response ( 73 , 74 ). In addition, several independent bioinformatics analyses have demonstrated that it is a valuable clinical prognostic biomarker in HCC ( 75 , 76 ) and lower-grade glioma ( 77 ). ZFPM2-AS1 is reported to be involved in numerous tumors, including lung adenocarcinoma ( 78 ), renal cell cancer ( 79 ), gastric carcinoma ( 80 ) and HCC ( 81 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of a Ferroptosis-Related Signature Model Including mRNAs and lncRNAs for Predicting Prognosis and Immune Activity in Hepatocellular Carcinoma

et al. 2021

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BackgroundFerroptosis is a novel form of regulated cell death involved in tumor progression. The role of ferroptosis-related lncRNAs in hepatocellular carcinoma (HCC) remains unclear.MethodsRNA-seq and clinical data for HCC patients were downloaded from The Cancer Genome Atlas (TCGA) Genomic Data Commons (GDC) portal. Bioinformatics methods, including weighted gene coexpression network analysis (WGCNA), Cox regression, and least absolute shrinkage and selection operator (LASSO) analysis, were used to identify signature markers for diagnosis/prognosis. The tumor microenvironment, immune infiltration and functional enrichment were compared between the low-risk and high-risk groups. Subsequently, small molecule drugs targeting ferroptosis-related signature components were predicted via the L1000FWD and PubChem databases.ResultsThe prognostic model consisted of 2 ferroptosis-related mRNAs (SLC1A5 and SLC7A11) and 8 ferroptosis-related lncRNAs (AC245297.3, MYLK-AS1, NRAV, SREBF2-AS1, AL031985.3, ZFPM2-AS1, AC015908.3, MSC-AS1). The areas under the curves (AUCs) were 0.830 and 0.806 in the training and test groups, respectively. Decision curve analysis (DCA) revealed that the ferroptosis-related signature performed better than all pathological characteristics. Multivariate Cox regression analysis showed that the risk score was an independent prognostic factor. The survival probability of low- and high-risk patients could be clearly distinguished by the principal component analysis (PCA) plot. The risk score divided HCC patients into two distinct groups in terms of immune status, especially checkpoint gene expression, which was further supported by the Gene Ontology (GO) biological process, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Finally, several small molecule drugs (SIB-1893, geldanamycin and PD-184352, etc) targeting ferroptosis-related signature components were identified for future reference.ConclusionWe constructed a new ferroptosis-related mRNA/lncRNA signature for HCC patients. The model can be used for prognostic prediction and immune evaluation, providing a reference for immunotherapies and targeted therapies.

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Section: Discussionmentioning

confidence: 99%

Identification of a Ferroptosis-Related Signature Model Including mRNAs and lncRNAs for Predicting Prognosis and Immune Activity in Hepatocellular Carcinoma

et al. 2021

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“…This may help explain why many successful preclinical responses are not reproduced after entering real clinical trials. In addition, compared with other studies using the TCGA database to develop lncRNA prognostic models (13)(14)(15)(16)(17)(18), our HCCSenLncSig model is comparable. This shows that the senescent cells in the TME are helpful in predicting the prognosis of HCC, and are at least as valuable as other biomarkers.…”

Section: Discussionmentioning

confidence: 83%

“…A high level of LINC00958 aggravated HCC lipogenesis and progression through sponging miR-3619-5p, further upregulating the hepatoma-derived growth factor expression (12). Although several lncRNA prognostic models for HCC have been developed (13)(14)(15)(16)(17)(18), the potential immune microenvironment predictive ability and therapeutic guidance of the models, especially for immunotherapy, have yet to be evaluated.…”

Section: Introductionmentioning

confidence: 99%

The development and validation of a novel senescence-related long-chain non-coding RNA (lncRNA) signature that predicts prognosis and the tumor microenvironment of patients with hepatocellular carcinoma

Huang¹,

Ma²,

Zhou³

et al. 2022

Ann Transl Med

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Background: The epigenetic regulators of cellular senescence, especially long non-coding RNAs (lncRNAs), remain unclear. The expression levels of lncRNA were previously known to be prognostic indicators for tumors. We hypothesized that lncRNAs regulating cellular senescence could also predict prognosis in patients with hepatocellular carcinoma (HCC) and developed a novel lncRNA predictive signature.Methods: Using RNA sequencing data from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) database, a co-expression network of senescence-related messenger RNAs (mRNAs) and lncRNAs was constructed. Using univariate Cox regression analysis and a stepwise multiple Cox regression analysis, we constructed a prognostic HCC senescence-related lncRNA signature (HCCSenLncSig).Kaplan-Meier analysis was used to compare the overall survival (OS) of high-and low-risk groups stratified by the HCCSenLncSig. Furthermore, the HCCSenLncSig risk score and other clinical characteristics were included to develop an HCC prognostic nomogram. The accuracy of the model was evaluated by the time dependent receiver operating characteristic (ROC) and calibration curves, respectively.

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“…AC099850.4 is one of the top lncRNA in miRNA-lncRNA network and may be associated with tumor division, tumor proliferation, cell cycle and so on in ovarian cancer (Zhao et al, 2020). Higher expression of NRAV was associated with advanced clinical stage, poor prognosis and immunologic characteristics in hepatocellular carcinoma patients (Feng et al, 2021;Xu et al, 2021). However, to date, there are few studies on these lncRNAs in hepatocellular carcinoma under hypoxia.…”

Section: Discussionmentioning

confidence: 99%

Identification and Validation of Hypoxia-Related lncRNA Signature as a Prognostic Model for Hepatocellular Carcinoma

Zhou

Zhang

2021

Front. Genet.

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Hepatocellular carcinoma (HCC) is one of the most general malignant tumors. Hypoxia is a critical clinical characteristic and acts as a significant part in the development and cancers’ prognosis. The prognostic value and biological functions of hypoxia-related lncRNAs in hepatocellular carcinoma is little known. Thus, we aim to establish a hypoxia-related lncRNA signature to predict the HCC patients’ survival. First, we extracted the hypoxia-related genes and expression of lncRNAs from the MSigDB and TCGA database, respectively. The co-expression analysis among hypoxia-related mRNAs and lncRNAs was employed to identify hypoxia-related lncRNAs. Then, comprehensive analyses of lncRNAs expression level and survival data were applied to establish the signature. We built a prognostic signature on the foundation of the three differently expressed hypoxia-related lncRNAs. Kaplan-Meier curves indicated the low-risk group is associated with better survival. The 1−, 3−, and 5 years AUC values of the signature were 0.805, 0.672 and 0.63 respectively. The test set performed consistent outcomes. A nomogram was built grounded on the risk score and clinicopathological features. GSEA showed the immune-related pathways in high-risk group, while metabolism-related pathways in low-risk group. Besides, we found this model was correlated with the clinical features, tumor immune cell infiltration, immune checkpoints, and m6A-related genes. Finally, a novel signature based on hypoxia-related lncRNAs was established and validated for predicting HCC patients’ survival and may offer some useful information for immunotherapies.

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Genome-Wide Screening Identifies Prognostic Long Noncoding RNAs in Hepatocellular Carcinoma

Cited by 17 publications

References 38 publications

Identification of a Ferroptosis-Related Signature Model Including mRNAs and lncRNAs for Predicting Prognosis and Immune Activity in Hepatocellular Carcinoma

Identification of a Ferroptosis-Related Signature Model Including mRNAs and lncRNAs for Predicting Prognosis and Immune Activity in Hepatocellular Carcinoma

The development and validation of a novel senescence-related long-chain non-coding RNA (lncRNA) signature that predicts prognosis and the tumor microenvironment of patients with hepatocellular carcinoma

Identification and Validation of Hypoxia-Related lncRNA Signature as a Prognostic Model for Hepatocellular Carcinoma

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