Big Data-Based Identification of Multi-Gene Prognostic Signatures in Liver Cancer

Liu, Meiliang; Liu, Xia; Liu, Shun; Xiao, Feifei; Guo, Erna; Qin, Xiaoxia; Wu, Liuyu; Liang, Qiwei; Liang, Zerui; Li, Kehua; Zhang, Di; Yu, Yang; Luo, Xingxi; Lei, Lei; Tan, Jennifer Hui Juan; Yin, Fuqiang; Zeng, Xianmin

doi:10.3389/fonc.2020.00847

Cited by 10 publications

(7 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…G6PD, an important rate-limiting enzyme of the pentose phosphate, was essential for tumor growth ( Tang et al, 2015 ). GOT2 was proven to be related to the metabolism of tumor cells ( Wang et al, 2021 ), low GOT2 expression was detected in liver tumor tissues, and its downregulation was correlated with worse prognosis ( Liu et al, 2020 ). These findings were in agreement with our established risk model in this study.…”

Section: Discussionmentioning

confidence: 99%

Effects of Glycolysis-Related Genes on Prognosis and the Tumor Microenvironment of Hepatocellular Carcinoma

et al. 2022

View full text Add to dashboard Cite

Background: Hepatocellular carcinoma (HCC) is a common and deadly malignancy worldwide. Current treatment methods for hepatocellular carcinoma have many disadvantages; thus, it is urgent to improve the efficacy of these therapies. Glycolysis is critical in the occurrence and development of tumors. However, survival and prognosis biomarkers related to glycolysis in HCC patients remain to be fully identified.Methods: Glycolysis-related genes (GRGs) were downloaded from “The Molecular Signatures Database” (MSigDB), and the mRNA expression profiles and clinical information of HCC patients were obtained from TCGA. Consensus clustering was performed to classify the HCC patients into two subgroups. We used the least absolute shrinkage and selection operator (LASSO) regression analysis to construct the risk signature model. Kaplan–Meier (K-M) survival analysis was performed to evaluate the prognostic significance of the risk model, and the receiver operating characteristic (ROC) curve analysis was used to evaluate the prediction accuracy. The independent prediction ability of the risk model was validated by univariate and multivariate Cox regression analyses. The differences of immune infiltrates and relevant oncogenic signaling between different risk groups were compared. Finally, biological experiments were performed to explore the functions of screened genes.Results: HCC patients were classified into two subgroups, according to the expression of prognostic-related GRGs. Almost all GRGs categorized in cluster 2 showed upregulated expressions, whereas GRGs in cluster 1 conferred survival advantages. GSEA identified a positive correlation between cluster 2 and the glycolysis process. Ten genes were selected for risk signature construction. Patients were assigned to high-risk and low-risk groups based on the median risk score, and K-M survival analysis indicated that the high-risk group had a shorter survival time. Additionally, the risk gene signature can partially affect immune infiltrates within the HCC microenvironment, and many oncogenic pathways were enriched in the high-risk group, including glycolysis, hypoxia, and DNA repair. Finally, in vitro knockdown of ME1 suppressed proliferation, migration, and invasion of hepatocellular carcinoma cells.Conclusion: In our study, we successfully constructed and verified a novel glycolysis-related risk signature for HCC prognosis prediction, which is meaningful for classifying HCC patients and offers potential targets for the treatment of hepatocellular carcinoma.

show abstract

Section: Discussionmentioning

confidence: 99%

Effects of Glycolysis-Related Genes on Prognosis and the Tumor Microenvironment of Hepatocellular Carcinoma

et al. 2022

View full text Add to dashboard Cite

show abstract

“…8 For example, a previously reported regular survival analysis of 2887 liver cancer patients has concluded that the 1-, 3-, and 5-year survival rates are 49.3%, 26.6%, and 19.5%, respectively. 9 Nevertheless, it has been demonstrated that cancer patients who already survived 3 years have an additional 1-year CS of 93.7%, and those who already survived 5 years have an additional 1-year CS of 91%. 10 Therefore, CS analysis may provide more detailed and meaningful prognostic information for those who survived the previous management.…”

Section: Introductionmentioning

confidence: 99%

A novel prognostic time window based on conditional survival and outcomes analyses of primary liver cancer patients

Hong

Qiu

et al. 2022

Cancer Medicine

View full text Add to dashboard Cite

BackgroundLiver cancer is one of the most deadly and prevalent cancers. A routine follow‐up plan for liver cancer is crucial but limited. In the present study, we aimed to disclose possible risk factors and critical survival time windows for primary liver cancer.MethodsWe enrolled 692 liver cancer patients from Sun Yat‐sen University Cancer Center (SYSUCC). Univariate and multivariate logistic regression analyses of cirrhosis and recurrence were conducted. A meta‐analysis was utilized to validate an indication of creatinine (CRE) in recurrence. Conditional survival analysis was performed using the Kaplan–Meier method. The results were further verified by the SYSUCC validation cohort and Surveillance, Epidemiology, and End Results (SEER) validation cohort.ResultsOur results indicated that A/G, history of hepatitis, history of alcohol consumption and platelet (PLT) might be potential prognostic factors for cirrhosis in liver cancer patients. CRE was significantly correlated with recurrence due to various therapies, especially after transarterial embolization. Moreover, 1.5 years to 2 years may be a critical time window for deterioration in survival rate based on the conditional survival analysis.ConclusionA/G, history of hepatitis, alcohol consumption and PLT may be potential prognostic factors for cirrhosis in liver cancer patients. More attention should be focused on the renal function when treating the patients due to the significant role of CRE. 1.5 years to 2 years is a critical time window for deterioration in survival rate for liver cancer patients that contributes to determining the optimal follow‐up plan in the future.

show abstract

“…GOT2 , situated on chromosome 16q21, is a crucial enzyme for cancer cell metabolism, (i) mediating the reversible interconversion of oxaloacetate and glutamate into aspartate and α-ketoglutarate, providing energy for tumor cells (Krebs cycle) [ 29 ]; (ii) being a key transfer enzyme in the malate-aspartate NADH shuttle activity and oxidative protection [ 30 ], maintaining glycolysis, and (iii) participating in the amino acid metabolism of tumor cells [ 31 ]. Increasing evidence has shown that dysregulation of GOT2 expression significantly influences tumor growth and the prognosis of several human neoplasms [ 30 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ]. However, the role of GOT2 in the development and prognosis of KIRC has not been reported.…”

Section: Introductionmentioning

confidence: 99%

Expression of GOT2 Is Epigenetically Regulated by DNA Methylation and Correlates with Immune Infiltrates in Clear-Cell Renal Cell Carcinoma

Ferreira

Oliveira

2022

CIMB

View full text Add to dashboard Cite

Clear cell renal cell carcinoma (KIRC) is the most common and highly malignant pathological type of kidney cancer, characterized by a profound metabolism dysregulation. As part of aspartate biosynthesis, mitochondrial GOT2 (glutamic-oxaloacetic transaminase 2) is essential for regulating cellular energy production and biosynthesis, linking multiple pathways. Nevertheless, the expression profile and prognostic significance of GOT2 in KIRC remain unclear. This study comprehensively analyzed the transcriptional levels, epigenetic regulation, correlation with immune infiltration, and prognosis of GOT2 in KIRC using rigorous bioinformatics analysis. We discovered that the expression levels of both mRNA and protein of GOT2 were remarkably decreased in KIRC tissues in comparison with normal tissues and were also significantly related to the clinical features and prognosis of KIRC. Remarkably, low GOT2 expression was positively associated with poorer overall survival (OS) and disease-free survival (DFS). Further analysis revealed that GOT2 downregulation is driven by DNA methylation in the promoter-related CpG islands. Finally, we also shed light on the influence of GOT2 expression in immune cell infiltration, suggesting that GOT2 may be a potential prognostic marker and therapeutic target for KIRC patients.

show abstract

Big Data-Based Identification of Multi-Gene Prognostic Signatures in Liver Cancer

Cited by 10 publications

References 48 publications

Effects of Glycolysis-Related Genes on Prognosis and the Tumor Microenvironment of Hepatocellular Carcinoma

Effects of Glycolysis-Related Genes on Prognosis and the Tumor Microenvironment of Hepatocellular Carcinoma

A novel prognostic time window based on conditional survival and outcomes analyses of primary liver cancer patients

Expression of GOT2 Is Epigenetically Regulated by DNA Methylation and Correlates with Immune Infiltrates in Clear-Cell Renal Cell Carcinoma

Contact Info

Product

Resources

About