Dataset Information

A three-gene signature reveals changes in the tumor immune microenvironment in the progression from NAFLD to HCC.

ABSTRACT: Hepatocellular carcinoma (HCC) is one of the most dangerous malignant tumors. The incidence rates of obesity related NAFLD and NASH are increasing year by year, and they are the main risk factors for HCC at present. Finding the mechanism of malignant transformation of NAFLD and NASH is helpful for early prevention and diagnosis. In this study, we performed differential analysis using NAFLD data, NASH data, and HCC data to identify crossover differential genes. Then, using the clinical data of TCGA, a prognostic risk prediction model of three genes (TEAD4, SOCS2, CIT) was constructed, and survival analysis and receiver operating characteristic curves were drawn. The prognostic model was validated using ICGC, GSE116174 and GSE54236 datasets. In addition, we assessed immune status and function in high- and low-risk populations using a prognostic model. Moreover, we assessed the expression of CIT in clinical samples and HCC cell lines and validated its role in HCC development. Our study elucidates the important role of the tumor immune microenvironment in the development of NAFLD/NASH to HCC, deepens the understanding of the pathogenesis of NAFLD/NASH development to HCC, and is helpful for clinical management and decision-making.

SUBMITTER: Liu L

PROVIDER: S-EPMC10724126 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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A three-gene signature reveals changes in the tumor immune microenvironment in the progression from NAFLD to HCC.

Liu Lijuan L Tang Haonan H Wang Kui K Liu Jiaying J Luo Ningbin N Jin Guanqiao G

Scientific reports 20231215 1

Hepatocellular carcinoma (HCC) is one of the most dangerous malignant tumors. The incidence rates of obesity related NAFLD and NASH are increasing year by year, and they are the main risk factors for HCC at present. Finding the mechanism of malignant transformation of NAFLD and NASH is helpful for early prevention and diagnosis. In this study, we performed differential analysis using NAFLD data, NASH data, and HCC data to identify crossover differential genes. Then, using the clinical data of TC ...[more]

PMID: 38102321

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Project description:BackgroundThe incidence of malignant melanoma accounts for only approximately 5% of skin malignant tumors, however, it accounts for 75% of its mortality. Long-chain non-coding RNA (lncRNA) has a wide range of functional activities. Disorders of lncRNAs may lead to the occurrence and development of melanoma, and may also be related to immunotherapy.MethodsThe transcriptomic data of primary and metastatic melanoma patients and 331 immune-related genes were downloaded from skin cutaneous melanoma (SKCM) in the The Cancer Genome Atlas (TCGA) database. On this basis, 460 immunologically relevant lncRNAs were identified by constructing a co-expression network of immunogenic genes and lncRNAs in primary and metastatic melanoma patients. Prognostic genes were screened using univariate Cox regression analysis. ROC analysis was performed to evaluate the robustness of the prognostic signature.ResultsUnivariate correlation analysis showed that only 3 of the 23 immune-related lncRNAs were at high risk and the rest were at low risk. Signatures of 7 immune-related lncRNAs were identified by multivariate correlation analysis. The clinical correlation analysis showed that the 7 immune-related lncRNAs were associated with the clinical stage of primary and metastatic melanoma. Principal component analysis (PCA) showed that only 7 immune-related lncRNA signals divided tumor patients into high-risk and low-risk groups, while the low-risk group was enriched in the immune system process M13664 and immune response M19817 sets. PPI interaction network analysis showed that 11 G protein-coupled receptors and 6 corresponding ligands in the 2 gene sets affected the tumor microenvironment and were negatively related to the risk of the 7 immune-related lncRNAs. The tumor microenvironment immune cell infiltration analysis also supported the finding that anti-tumor immunity in the low-risk group was stronger than in the high-risk group.ConclusionsThese results indicate that characteristics of the 7 immune-related lncRNAs have prognostic value for melanoma patients and can be used as potential immunotherapy targets.

Dataset Information

A three-gene signature reveals changes in the tumor immune microenvironment in the progression from NAFLD to HCC.

Publications

A three-gene signature reveals changes in the tumor immune microenvironment in the progression from NAFLD to HCC.

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