Correlation of LAGE3 with unfavorable prognosis and promoting tumor development in HCC via PI3K/AKT/mTOR and Ras/RAF/MAPK pathways

Li, Yun; Xiong, Hui

doi:10.1186/s12885-022-09398-3

Cited by 10 publications

(5 citation statements)

References 44 publications

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“…The study of Li et al. showed that LAGE3 has prognostic value in HCC, which may affect the progression path of HCC tumor by promoting the proliferation, survival, migration, invasion and anti-apoptosis of HCC cells through the PI3K/AKT/mTOR and Ras/RAF/MAPK pathways ( 53 ). Guo et al.…”

Section: Discussionmentioning

confidence: 99%

Single-cell transcriptome analysis reveals the metabolic changes and the prognostic value of malignant hepatocyte subpopulations and predict new therapeutic agents for hepatocellular carcinoma

et al. 2023

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BackgroundThe development of HCC is often associated with extensive metabolic disturbances. Single cell RNA sequencing (scRNA-seq) provides a better understanding of cellular behavior in the context of complex tumor microenvironments by analyzing individual cell populations. MethodsThe Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data was employed to investigate the metabolic pathways in HCC. Principal component analysis (PCA) and uniform manifold approximation and projection (UMAP) analysis were applied to identify six cell subpopulations, namely, T/NK cells, hepatocytes, macrophages, endothelial cells, fibroblasts, and B cells. The gene set enrichment analysis (GSEA) was performed to explore the existence of pathway heterogeneity across different cell subpopulations. Univariate Cox analysis was used to screen genes differentially related to The Overall Survival in TCGA-LIHC patients based on scRNA-seq and bulk RNA-seq datasets, and LASSO analysis was used to select significant predictors for incorporation into multivariate Cox regression. Connectivity Map (CMap) was applied to analysis drug sensitivity of risk models and targeting of potential compounds in high risk groups.ResultsAnalysis of TCGA-LIHC survival data revealed the molecular markers associated with HCC prognosis, including MARCKSL1, SPP1, BSG, CCT3, LAGE3, KPNA2, SF3B4, GTPBP4, PON1, CFHR3, and CYP2C9. The RNA expression of 11 prognosis-related differentially expressed genes (DEGs) in normal human hepatocyte cell line MIHA and HCC cell lines HCC-LM3 and HepG2 were compared by qPCR. Higher KPNA2, LAGE3, SF3B4, CCT3 and GTPBP4 protein expression and lower CYP2C9 and PON1 protein expression in HCC tissues from Gene Expression Profiling Interactive Analysis (GEPIA) and Human Protein Atlas (HPA) databases. The results of target compound screening of risk model showed that mercaptopurine is a potential anti-HCC drug.ConclusionThe prognostic genes associated with glucose and lipid metabolic changes in a hepatocyte subpopulation and comparison of liver malignancy cells to normal liver cells may provide insight into the metabolic characteristics of HCC and the potential prognostic biomarkers of tumor-related genes and contribute to developing new treatment strategies for individuals.

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Section: Discussionmentioning

confidence: 99%

Single-cell transcriptome analysis reveals the metabolic changes and the prognostic value of malignant hepatocyte subpopulations and predict new therapeutic agents for hepatocellular carcinoma

et al. 2023

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“…In many cases, the aggressive and unintentional spread of cancer is caused by erroneous phenotypes that result from DNA replication [61]. It is possible to effectively analyze the PI3K/AKT/mTOR signaling pathway as an appropriate treatment option because it is connected with several elements of cell growth and survival and is commonly activated in many different types of cancer [62]. The PI3K/AKT/mTOR axis can exhibit oncogenic activity by blocking autophagy and senescence processes while concurrently promoting cell growth, survival, migration, and invasiveness [63,64].…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of cuproptosis-related lncRNAs in immune infiltration and prognosis in hepatocellular carcinoma

Liu

Lai³

et al. 2023

BMC Bioinformatics

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Background Being among the most common malignancies worldwide, hepatocellular carcinoma (HCC) accounting for the third cause of cancer mortality. The regulation of cell death is the most crucial step in tumor progression and has become a crucial target for nearly all therapeutic options. Cuproptosis, a copper-induced cell death, was recently reported in Science. However, its primary function in carcinogenesis is still unclear. Methods Cuproptosis-related lncRNAs significantly associated with overall survival (OS) were screened by stepwise univariate Cox regression. The signature of cuproptosis-related lncRNAs for HCC prognosis was constructed by the LASSO algorithm and multivariate Cox regression. Further Kaplan–Meier analysis, proportional hazards model, and ROC analysis were performed. Functional annotation was performed using gene set enrichment analysis (GSEA). The relationship between prognostic cuproptosis-related lncRNAs and HCC prognosis was further explored by GEPIA(http://gepia.cancer-pku.cn/) online analysis tool. Finally, we used the ESTIMATE and XCELL algorithms to estimate stromal and immune cells in tumor tissue and cast each sample to infer the underlying mechanism of cuproptosis-related lncRNAs in the tumor immune microenvironment (TIME) of HCC patients. Results Four cuproptosis-related lncRNAs were used to construct a prognostic lncRNA signature, which was an independent factor in predicting OS in HCC patients. Kaplan–Meier curves showed significant differences in survival rates between risk subgroups (p = 0.002). At the same time, we found that the expression levels of most immune checkpoint genes increased with increasing risk scores. Tumorigenesis and immunological-related pathways were primarily enhanced in the high-risk group, as determined by GSEA. The results of drug sensitivity analysis showed that compared with patients in the high-risk group, the IC50 values of erlotinib and lapatinib were lower in patients in the low-risk group, while the opposite was true for sunitinib, paclitaxel, gemcitabine, and imatinib. We also found that elevated AL133243.2 expression was significantly associated with worse OS and disease-free survival (DFS), more advanced T stage and higher tumor grade, and reduced immune cell infiltration, suggesting that HCC patients with low AL133243.2 expression in tumor tissues may have a better response to immunotherapy. Conclusion Collectively, the cuproptosis-associated lncRNA signature can serve as an independent predictor to guide individual treatment strategies. Furthermore, AL133243.2 is a promising marker for predicting immunotherapy response in HCC patients. This data may facilitate further exploration of more effective immunotherapy strategies for HCC.

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“…In many cases, the aggressive and unintentional spread of cancer is caused by erroneous phenotypes that result from DNA replication (43). It is possible to effectively analyze the PI3K/AKT/mTOR signaling pathway as an appropriate treatment option because it is connected with several elements of cell growth and survival and is commonly activated in many different types of cancer (44). The PI3K/AKT/mTOR axis can exhibit oncogenic activity by blocking autophagy and senescence processes while concurrently promoting cell growth, survival, migration, and invasiveness (45,46).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of Cuproptosis-Related lncRNAs in Immune Infiltration and Prognosis in Hepatocellular Carcinoma

Liu¹,

Wu²,

Lai³

et al. 2022

Preprint

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Background Being among the most common malignancies worldwide, hepatocellular carcinoma (HCC) accounts now as the fourth primary reason for cancer death. The regulation of cell death is the most crucial step in tumor progression and has become a crucial target for nearly all therapeutic options. Cuproptosis is a lately discovered copper-dependent method of apoptosis regulation. However, its primary function in carcinogenesis is still unclear. Results We developed a signature consisted of four cuproptosis-related lncRNAs (AL133243.2, AL031985.3, AL137127.1, and SNHG18). Compared to the low-risk group, the high-risk group exhibited a poorer outcome. The cuproptosis-related lncRNA signature can estimate HCC patients’ fate independently. Tumorigenesis and immunological-related pathways were primarily enhanced in the high-risk group, as determined by GSEA. Immunotherapy and standard chemotherapy medications such as erlotinib and lapatinib were more suitable for low-risk patients, whereas sunitinib, paclitaxel, gemcitabine, and imatinib were more suitable for high-risk patients. Conclusion The prognostic signature may forecasting HCC patients’ prognosis and establishes the fundamental function of cuproptosis-related lncRNAs in HCC. Cuproptosis-related lncRNAs may perform an important part in the tumor immune microenvironment (TIME), making them a promising treatment for HCC patients.

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Correlation of LAGE3 with unfavorable prognosis and promoting tumor development in HCC via PI3K/AKT/mTOR and Ras/RAF/MAPK pathways

Cited by 10 publications

References 44 publications

Single-cell transcriptome analysis reveals the metabolic changes and the prognostic value of malignant hepatocyte subpopulations and predict new therapeutic agents for hepatocellular carcinoma

Single-cell transcriptome analysis reveals the metabolic changes and the prognostic value of malignant hepatocyte subpopulations and predict new therapeutic agents for hepatocellular carcinoma

Comprehensive analysis of cuproptosis-related lncRNAs in immune infiltration and prognosis in hepatocellular carcinoma

Comprehensive Analysis of Cuproptosis-Related lncRNAs in Immune Infiltration and Prognosis in Hepatocellular Carcinoma

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