Bioinformatics analysis explores potential hub genes in nonalcoholic fatty liver disease

Wu, Chutian; Zhou, Yun; Wang, Min; Dai, Guolin; Liu, Xiongxiu; Lai, Leizhen; Tang, Shaohui

doi:10.21203/rs.3.rs-929980/v1

“…Finally, the dynamic tree cut algorithm was applied to the dendrogram for module identification with the minisize of module gene numbers set as 50, and similar modules were merged following a height cutoff of 0.25. In the module-trait analysis, gene-trait significance (GS) value > 0.3 and module membership (MM) value > 0.55 were defined as a threshold 17 . Then, Venn diagram was performed to explore the trait-expression-related genes.…”

Section: Weighted Gene Co-expression Network Analysis (Wgcna)mentioning

confidence: 99%

Identification of potential biomarkers in Barrett’s esophagus derived esophageal adenocarcinoma

Yi

¹

,

Zhao

²

,

He

³

et al. 2023

Sci Rep

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Almost 50% of esophageal adenocarcinoma (EAC) patients progressed from Barrett’s esophagus (BE). EAC is often diagnosed at late stages and is related to dismal prognosis. However, there are still no effective methods for stratification and therapy in BE and EAC. Two public datasets (GSE26886 and GSE37200) were analyzed to identify differentially expressed genes (DEGs) between BE and EAC. Then, a series of bioinformatics analyses were performed to explore potential biomarkers associated with BE-EAC. 27 up- and 104 down-regulated genes were observed between GSE26886 and GSE37200. The GO and KEGG enrichment analysis indicated that the DEGs were highly involved in tumorigenesis. Subsequently, Weighted Gene Co-Expression Network Analysis (WGCNA) were performed to explore the potential genes related to BE-EAC, which were validated in The Cancer Genome Atlas (TCGA) database, and 5 up-regulated genes (MYO1A, ACE2, COL1A1, LGALS4, and ADRA2A) and 3 down-regulated genes (AADAC, RAB27A, and P2RY14) were found in EAC. Meanwhile, ADRA2A and AADAC could contribute to EAC pathogenesis and progression. MYO1A, ACE2, COL1A1, LGALS4, ADRA2A, AADAC, RAB27A, and P2RY14 could be potential novel diagnostic and prognostic biomarkers in BE-EAC.

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“…Cur-rently, sensitive biomarkers for the diagnosis of NAFLD are still lacking, and liver biopsies, as an invasive method, are still considered the gold standard for diagnosis and prognosis [4]. Although numerous studies have attempted to study the pathogenesis and progression of NAFLD, there are still no effective drugs for NAFLD other than lifestyle changes [5]. Moreover, the development of NAFLD is a complex process and is still not sufficiently explained [6].…”

Section: Introductionmentioning

confidence: 99%

Identification of Cuproptosis-Related Genes in Nonalcoholic Fatty Liver Disease

Wu

¹

,

Liu

²

,

Zhong

³

et al. 2023

Oxidative Medicine and Cellular Longevity

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Nonalcoholic fatty liver disease (NAFLD) is the most prevalent hepatic pathology worldwide. However, the precise molecular mechanisms for NAFLD are still not sufficiently explained. Recently, a new mode of cell death (cuproptosis) is found. However, the relationship between NAFLD and cuproptosis remains unclear. We analyzed three public datasets (GSE89632, GSE130970, and GSE135251) to identify cuproptosis-related genes stably expressed in NAFLD. Then, we performed a series of bioinformatics analyses to explore the relationship between NAFLD and cuproptosis-related genes. Finally, 6 high-fat diet- (HFD-) induced NAFLD C57BL/6J mouse models were established to carry out transcriptome analysis. The results of gene set variation analysis (GSVA) revealed that the cuproptosis pathway was abnormally activated to a certain degree ( p = 0.035 in GSE89632, p = 0.016 in GSE130970, p = 0.22 in GSE135251), and the principal component analysis (PCA) of the cuproptosis-related genes showed that the NAFLD group separated from the control group, with the first two principal components accounting for 58.63%-74.88% of the variation. Among three datasets, two cuproptosis-related genes (DLD and PDHB, p < 0.01 or 0.001) were stably upregulated in NAFLD. Additionally, both DLD ( AUC = 0.786 – 0.856 ) and PDHB ( AUC = 0.771 – 0.836 ) had favorable diagnostic properties, and the multivariate logistics regression model further improved the diagnostic properties ( AUC = 0.839 – 0.889 ). NADH, flavin adenine dinucleotide, and glycine targeted DLD, and pyruvic acid and NADH targeted PDHB in the DrugBank database. The DLD and PDHB were also associated with clinical pathology, especially with steatosis (DLD, p = 0.0013 – 0.025 ; PDHB, p = 0.002 – 0.0026 ) and NAFLD activity score (DLD, p = 0.004 – 0.02 ; PDHB, p = 0.003 – 0.031 ). What is more, DLD and PDHB were correlated with stromal score (DLD, R = 0.38 , p < 0.001 ; PDHB, R = 0.31 , p < 0.001 ) and immune score (DLD, R = 0.26 , p < 0.001 ; PDHB, R = 0.27 , p < 0.001 ) in NAFLD. Furthermore, Dld and Pdhb were also significantly upregulated in the NAFLD mouse model. In conclusion, cuproptosis pathways, especially DLD and PDHB, could be potential candidate genes for NAFLD diagnostic and therapeutic options.

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“…Several studies have explored genes and potential biomarkers involved in NASH and HCC progression (Jiang, et al 2021, Li, et al 2017, Song, et al 2020, Wu, et al 2021). Yet, very few have analyzed those connected with NASH progression to NASH-related HCC, and due to the heterogeneous speci city of available diagnostic and prognostic biomarkers, recurrence and metastasis in patients of different races, cancer stages, genders, age groups, and weights remain inadequately addressed(2017, Li and Wang 2016, Shimada, et al 2019).…”

Section: Introductionmentioning

confidence: 99%

Novel diagnostic, therapeutic, and prognostic biomarkers for nonalcoholic steatohepatitis-derived hepatocellular carcinoma: Capable to overcome the heterogeneity-specific barrier

Qi

¹

,

Huang

²

2022

Preprint

0

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Recent years have seen a rapid increase in the incidence of nonalcoholic steatohepatitis (NASH)-derived liver cancer, the heterogeneity-specific nature of biomarkers is significantly contributing to the high mortality rate worldwide. Objective: To screen new pathogenic genes associated with nonalcoholic steatohepatitis-derived hepatocellular carcinoma (NASH-related HCC) and related pathways, and break through the heterogeneity barrier. Methods: Differentially expressed genes (DEGs) were screened using a gene expression chip. Gene Ontology (GO) and KEGG analyses were performed after. We then built protein-protein interaction (PPI) networks to identify hub gene. The diagnostic and prognostic role of the hub genes in NASH-related HCC patients of various clinicopathological features were revealed by a comprehensive bioinformatics approach. Results: The following 10 HUB genes were identified: YWHAZ, JUN, MDM2, ACTR3, HNRNPA2B1, FOS, CANX, RBBP4, RBFOX3, and RAC1. These genes were mainly enriched in pathways such as cell division, cell metabolism, protein binding. We further revealed that all the hub genes were significantly dysregulated in HCC patients of various clinicopathological features including different races, cancer stages, genders, age groups, and body weights. Additionally, some chemotherapeutic drugs were found to interact with hub gene. Conclusions: The genes identified in this study might play a crucial role in the progression of NASH to hepatocellular carcinoma and as potential biomarkers of NASH-HCC patients that could help to overcome the heterogenetic-specific barrier across different clinicopathological features.

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Bioinformatics analysis explores potential hub genes in nonalcoholic fatty liver disease

Cited by 3 publications

References 20 publications

Identification of potential biomarkers in Barrett’s esophagus derived esophageal adenocarcinoma

Identification of potential biomarkers in Barrett’s esophagus derived esophageal adenocarcinoma

Identification of Cuproptosis-Related Genes in Nonalcoholic Fatty Liver Disease

Novel diagnostic, therapeutic, and prognostic biomarkers for nonalcoholic steatohepatitis-derived hepatocellular carcinoma: Capable to overcome the heterogeneity-specific barrier

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