Computational Identification of Immune- and Ferroptosis-Related LncRNA Signature for Prognosis of Hepatocellular Carcinoma

Huang, Anmin; Li, Ting; Xie, Xueting; Xia, Jinglin

doi:10.3389/fmolb.2021.759173

Cited by 8 publications

(12 citation statements)

References 42 publications

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“…This five-FRL signature had a more stable predictive efficiency in both the training cohort and the testing cohort. Among them, LUCAT1 has been shown to directly sponge the onco-miR-181d-5p, and its upregulation is linked to a reduced risk of HCC recurrence [ 28 , 32 , 33 ]. AC015908.3 has been demonstrated to have a certain predictive value in the current model for predicting liver cancer prognosis [ 31 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

Prediction of Prognosis and Molecular Mechanism of Ferroptosis in Hepatocellular Carcinoma Based on Bioinformatics Methods

Xiong

Ouyang

Fang

et al. 2022

Computational and Mathematical Methods in Medicine

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Background. As an iron-dependent type of programmed cell death, ferroptosis plays an important role in the pathogenesis and progression of hepatocellular carcinoma (HCC). Long noncoding RNAs (lncRNAs) have been linked to the prognosis of patients with HCC in a number of studies. Nevertheless, the predictive value of lncRNAs (FRLs) associated with ferroptosis in HCC has not been fully elucidated. Methods. Download RNA sequencing data and clinical profiles of HCC patients from The Cancer Genome Atlas (TCGA) database. The FRLs associated with prognosis were determined by Pearson’s correlation analysis. After that, prognostic signature for FRLs was established using Cox and LASSO regression analyses. Meanwhile, survival analysis, correlation analysis of clinicopathological features, Cox regression, receiver operating characteristic (ROC) curve, and nomogram were used to analyze the FRL signature’s predictive capacity. The relationship between signature risk score, immune cell infiltration, and chemotherapy drug sensitivity is further studied.Results. In total, 93 FRLs were found to be of prognostic value in patients with HCC. A five-FRL signature comprising AC015908.3, LINC01138, AC009283.1, Z83851.1, and LUCAT1 was created in order to enhance the prognosis prediction with HCC patients. The signature demonstrated a good predictive potency, according to the Kaplan-Meier and ROC curves. The five-FRL signature was found to be a risk factor independent of various clinical factors using Cox regression and stratified survival analysis. The high-risk group was shown to be enriched in tumorigenesis and immune-related pathways according to GSEA analysis. Additionally, immune cell infiltration, immune checkpoint molecules, and half-inhibitory concentrations differed considerably between risk groups, implying that this signature could be used to evaluate the clinical efficacy of chemotherapy and immunotherapy. Conclusion. The five-FRL risk signature is helpful for assessing the prognosis of HCC patients and improving therapy options, so it can be further applied clinically.

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Section: Discussionmentioning

confidence: 99%

Prediction of Prognosis and Molecular Mechanism of Ferroptosis in Hepatocellular Carcinoma Based on Bioinformatics Methods

Xiong

Ouyang

Fang

et al. 2022

Computational and Mathematical Methods in Medicine

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“…Another approach is based on the interaction of ferroptosis and either long noncoding RNAs (lncRNAs) or miRNA as identified via in silico [ 116 , 117 , 124 ] or via in vitro/in vivo analyses [ 125 ].…”

Section: The Translation Of Ferroptosis Into Clinical Hcc Practicementioning

confidence: 99%

“…Next, Huang et al applied various bioinformatics methods to crystallize an immune- and ferroptosis-related lncRNA signature for the prognosis of HCC based on the following 17 candidate LncRNAs after filtration: AC009005.1, AC016773.1, AC090164.2, AC092119.2, AC099850.3, AL021807.1, AL356234.2, AL359510.2, CASC9, DUXAP8, GDNF-AS1, LINC01224, LINC01436, LINC02202, LUCAT1, PTGES2-AS1, and ZFPM2-AS1 [ 124 ].…”

Section: The Translation Of Ferroptosis Into Clinical Hcc Practicementioning

confidence: 99%

“…The application of the designed immune- and ferroptosis-related (IF) lncRNAs signature (finally on eight lncRNAs) predicts a worse outcome in patients with HCC that have a high IFlncRNA signature in comparison with those with a low IFlncRNA signature [ 124 ]. Comparable to the in-silico results of Wang et al the IFlncRNA signature could be correlated to inflammatory cell infiltrates and the expression of immune checkpoints highlighting the potential predictive potency of such an IFlncRNA signature for the response to immune checkpoint inhibitor treatments for HCC.…”

Section: The Translation Of Ferroptosis Into Clinical Hcc Practicementioning

confidence: 99%

“…Comparable to the in-silico results of Wang et al the IFlncRNA signature could be correlated to inflammatory cell infiltrates and the expression of immune checkpoints highlighting the potential predictive potency of such an IFlncRNA signature for the response to immune checkpoint inhibitor treatments for HCC. Interestingly, the comparison of the half maximal inhibitory concentration (IC50) of 30 anti-tumor drugs on patients with HCC and an IFlncRNA signature revealed that patients with high IFLSig should show no benefit from gefitinib, mitomycin, temsirolimus and erlotinib on the one hand, but a possible benefit from bexarotene, metformin, sorafenib, bleomycin and lapatinib on the other hand [ 124 ]. Therefore, the authors of this study suggested that IFLSig could help for the precise selecting chemotherapeutic drug against HCC in relation to the possible clinical benefit.…”

Section: The Translation Of Ferroptosis Into Clinical Hcc Practicementioning

confidence: 99%

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Ferroptosis in Hepatocellular Carcinoma: Mechanisms, Drug Targets and Approaches to Clinical Translation

Bekric

Ocker

Mayr

et al. 2022

Cancers

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Ferroptosis, an iron and reactive oxygen species (ROS)-dependent non-apoptotic type of regulated cell death, is characterized by a massive iron overload and peroxidation of polyunsaturated fatty acids (PUFAs), which finally results in cell death. Recent studies suggest that ferroptosis can influence carcinogenesis negatively and therefore may be used as a novel anti-cancer strategy. Hepatocellular carcinoma (HCC) is a deadly malignancy with poor chances of survival and is the second leading cause of cancer deaths worldwide. Diagnosis at an already late stage and general resistance to current therapies may be responsible for the dismal outcome. As the liver acts as a key factor in iron metabolism, ferroptosis is shown to play an important role in HCC carcinogenesis and, more importantly, may hold the potential to eradicate HCC. In this review, we summarize the current knowledge we have of the role of ferroptosis in HCC and the application of ferroptosis as a therapy option and provide an overview of the potential translation of ferroptosis in the clinical practice of HCC.

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A novel Cuproptosis-related LncRNA signature to predict prognosis in hepatocellular carcinoma

Zhang

Sun

Zhang

2022

Sci Rep

152

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Increased intracellular toxicity due to an imbalance in copper homeostasis caused by copper ion accumulation could regulate the rate of cancer cell growth and proliferation. The goal of this study was to create a novel Cuproptosis-related lncRNA signature that may be utilized to predict survival and immunotherapy in HCC patients. Cuproptosis-associated lncRNAs and differentially expressed lncRNAs between HCC tumor tissue and normal tissue were discovered first. By LASSO-Cox analysis, the overlapping lncRNAs were then utilized to build a Cuproptosis-associated lncRNA signature, which might be used to predict patient prognosis and responsiveness to immune checkpoint blockade (ICB) therapy. Differences in the infiltration of immune cell subpopulations between high and low-risk score subgroups were also analyzed. Moreover, a nomogram based on the Cuproptosis-associated lncRNA signature and clinical features was developed and demonstrated to have good predictive potential. Finally, qRT-PCR was performed in HerpG2 and MHCC-97H cell lines to explore whether these lncRNAs were indeed involved in the process of Cuproptosis. In summary, we created a prognostic lncRNA profile linked to Cuproptosis to forecast response to immunotherapy, which may provide a new potential non-apoptotic therapeutic perspective for HCC patients.

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Computational Identification of Immune- and Ferroptosis-Related LncRNA Signature for Prognosis of Hepatocellular Carcinoma

Cited by 8 publications

References 42 publications

Prediction of Prognosis and Molecular Mechanism of Ferroptosis in Hepatocellular Carcinoma Based on Bioinformatics Methods

Prediction of Prognosis and Molecular Mechanism of Ferroptosis in Hepatocellular Carcinoma Based on Bioinformatics Methods

Ferroptosis in Hepatocellular Carcinoma: Mechanisms, Drug Targets and Approaches to Clinical Translation

A novel Cuproptosis-related LncRNA signature to predict prognosis in hepatocellular carcinoma

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