Construction of a genome instability-derived lncRNA-based risk scoring system for the prognosis of hepatocellular carcinoma

Huang, Dan-Ping; Liao, Mianmian; Tong, Jingjing; Yuan, Weiqu; Peng, Deti; Lai, Jianping; Zeng, Yihao; Yi-jun, Qiu; Tong, Guangdong

doi:10.18632/aging.203698

Cited by 13 publications

(10 citation statements)

References 62 publications

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“…The patients with the highest and lowest 25% mutation frequencies were then assigned to GU (n = 93) and GS (n = 90) groups, respectively ( 26 ). Finally, 88 out of 1,362 lncRNAs were screened and identified as genomic instability-related lncRNAs (GILncRNAs) through the analysis of the gene expression differences between the GU and GS groups ( Table S2 ), which was consistent with previous studies ( 38 ). In the GU group, 56 genes showed an increased expression and 32 showed a decreased expression.…”

Section: Resultssupporting

confidence: 79%

Construction of a Novel LncRNA Signature Related to Genomic Instability to Predict the Prognosis and Immune Activity of Patients With Hepatocellular Carcinoma

et al. 2022

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BackgroundGenomic instability (GI) plays a crucial role in the development of various cancers including hepatocellular carcinoma. Hence, it is meaningful for us to use long non-coding RNAs related to genomic instability to construct a prognostic signature for patients with HCC.MethodsCombining the lncRNA expression profiles and somatic mutation profiles in The Cancer Genome Atlas database, we identified GI-related lncRNAs (GILncRNAs) and obtained the prognosis-related GILncRNAs through univariate regression analysis. These lncRNAs obtained risk coefficients through multivariate regression analysis for constructing GI-associated lncRNA signature (GILncSig). ROC curves were used to evaluate signature performance. The International Cancer Genomics Consortium (ICGC) cohort, and in vitro experiments were used for signature external validation. Immunotherapy efficacy, tumor microenvironments, the half-maximal inhibitory concentration (IC50), and immune infiltration were compared between the high- and low-risk groups with TIDE, ESTIMATE, pRRophetic, and ssGSEA program.ResultsFive GILncRNAs were used to construct a GILncSig. It was confirmed that the GILncSig has good prognostic evaluation performance for patients with HCC by drawing a time-dependent ROC curve. Patients were divided into high- and low-risk groups according to the GILncSig risk score. The prognosis of the low-risk group was significantly better than that of the high-risk group. Independent prognostic analysis showed that the GILncSig could independently predict the prognosis of patients with HCC. In addition, the GILncSig was correlated with the mutation rate of the HCC genome, indicating that it has the potential to measure the degree of genome instability. In GILncSig, LUCAT1 with the highest risk factor was further validated as a risk factor for HCC in vitro. The ESTIMATE analysis showed a significant difference in stromal scores and ESTIMATE scores between the two groups. Multiple immune checkpoints had higher expression levels in the high-risk group. The ssGSEA results showed higher levels of tumor-antagonizing immune cells in the low-risk group compared with the high-risk group. Finally, the GILncSig score was associated with chemotherapeutic drug sensitivity and immunotherapy efficacy of patients with HCC.ConclusionOur research indicates that GILncSig can be used for prognostic evaluation of patients with HCC and provide new insights for clinical decision-making and potential therapeutic strategies.

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Section: Resultssupporting

confidence: 79%

Construction of a Novel LncRNA Signature Related to Genomic Instability to Predict the Prognosis and Immune Activity of Patients With Hepatocellular Carcinoma

et al. 2022

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“…However, their functions and mechanisms of them have not been reported so far in HCC. AC145343.1 can be involved in the regulation of immune cell infiltration as TP53 mutation-associated lncRNA and predict HCC patient prognosis 43 , 44 . High GIHCG expression was linked to a shorter patient survival time and was also an independent predictive factor for overall survival in HCC 45 , which was in line with our findings.…”

Section: Discussionmentioning

confidence: 99%

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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“…A common mutation in HCC is in the tumor suppressor gene TP53, sometimes called P53. Tumor differentiation, vascular invasion, serum methemoglobin levels, and tumor staging are all impacted by TP53 mutations ( 58 , 59 ). A number of missense mutations within the TP53 gene’s DNA binding domain are tumor-promoting ( 60 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of a cuproptosis and copper metabolism gene–related lncRNAs prognostic signature associated with clinical and immunological characteristics of hepatocellular carcinoma

et al. 2023

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BackgroundThe relationship between cuproptosis and HCC is still in the exploratory stage. Long noncoding RNAs (lncRNAs) have recently been linked to the progression of hepatocellular carcinoma (HCC). However, the clinical significance of lncRNAs associated with cuproptosis remains unclear.MethodsBased on The Cancer Genome Atlas (TCGA) liver hepatocellular carcinoma (LIHC) dataset, we identified characteristic prognostic lncRNAs by univariate, LASSO, and multifactorial regression analysis, and constructed a prognostic signature of cuproptosis-related lncRNAs in HCC. The role of lncRNAs were identified through CCK-8, clone formation in Huh-7 cells with high expression of FDX1. Prognostic potential of the characteristic lncRNAs was evaluated in each of the two cohorts created by randomly dividing the TCGA cohort into a training cohort and a test cohort in a 1:1 ratio. Immune profiles in defined subgroups of cuproptosis-related lncRNA features as well as drug sensitivity were analyzed.ResultsWe constructed a multigene signature based on four characteristic prognostic lncRNAs (AL590705.3, LINC02870, KDM4A-AS1, MKLN1-AS). These four lncRNAs participated in the development of cuproptosis. HCC patients were classified into high-risk and low-risk groups based on the median value of the risk score. The receiver operating characteristic curve area under the curve values for 1-, 3-, and 5-year survival were 0.773, 0.728, and 0.647, respectively, for the training cohort, and 0.764, 0.671, and 0.662, respectively, for the test cohort. Univariate and multifactorial regression analyses indicated that this prognostic feature was an independent prognostic factor for HCC. Principal component analysis plots clearly distinguished between low- and high-risk patients in terms of their probability of survival. Furthermore, gene set enrichment analysis showed that a variety of processes associated with tumor proliferation and progression were enriched in the high-risk group compared with the low-risk group. Moreover, there were significant differences in the expression of immune cell subpopulations, immune checkpoint genes, and potential drug screening, which provided distinct therapeutic recommendations for individuals with various risks.ConclusionsWe constructed a novel cuproptosis-associated lncRNA signature with a significant predictive value for the prognosis of patients with HCC. Cuproptosis-associated lncRNAs are associated with the tumor immune microenvironment of HCC and even the efficacy of tumor immunotherapy.

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Construction of a genome instability-derived lncRNA-based risk scoring system for the prognosis of hepatocellular carcinoma

Cited by 13 publications

References 62 publications

Construction of a Novel LncRNA Signature Related to Genomic Instability to Predict the Prognosis and Immune Activity of Patients With Hepatocellular Carcinoma

Construction of a Novel LncRNA Signature Related to Genomic Instability to Predict the Prognosis and Immune Activity of Patients With Hepatocellular Carcinoma

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

Identification of a cuproptosis and copper metabolism gene–related lncRNAs prognostic signature associated with clinical and immunological characteristics of hepatocellular carcinoma

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