Pan-Cancer Analysis Shows That ALKBH5 Is a Potential Prognostic and Immunotherapeutic Biomarker for Multiple Cancer Types Including Gliomas

Cheng, Wei; Wang, Bo; Peng, Dazhao; Zhang, Xiaoyang; Li, Ze-Sheng; Luo, Lin; He, Yun; Liang, Hao; Du, Xuezhi; Li, Shenghui; Zhang, Shu; Zhang, Zhenyu; Han, Lei; Zhang, Jianning

doi:10.3389/fimmu.2022.849592

Cited by 55 publications

(43 citation statements)

References 76 publications

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“…In diabetic retinopathy, the change of ALKBH5 expression could cause m6A modi cation to be dysfunctional (72). In cancers, it was shown that ALKBH5 and its related genes were enriched in the in ammatory, metabolic, and immune signaling pathways in gliomas, suggesting that ALKBH5 might be a potential treatment for this disease (73). However, there is no relative study to explore how ALKBH5 works in PCOS through in ammations in PCOS.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome Profiling Revealed the Relationship Between Immune-Related Genes and m6A Modifiers in Polycystic Ovary Syndrome

Kong

Zhou

et al. 2022

Preprint

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Background Polycystic ovary syndrome (PCOS) is a common female endocrinal disease that may result in excessive androgen, but the mechanism of PCOS remains unclear. Most patients with PCOS suffer from low-grade inflammation, whereas the underlying connection between immune and PCOS is still uncertain. Objective This study aimed to determine the immune-related mechanisms behind PCOS pathogenesis and explore distinct immune-related genes and their functional signatures in PCOS. Methods The microarray dataset GSE155489 was downloaded from the Gene Expression Omnibus (GEO) database. The immune-related genes were downloaded from ImmPort. The immune-related differential expression genes (IRDEGs) in PCOS were screened, and functional and pathway enrichment analyses were applied. The protein-protein interactions (PPI), module analysis, and transcription factor enrichment analysis (TFEA) were used to identify hub genes. The immune profile analysis was depicted, and the expression correlation analysis between hub genes and m6A modifiers in PCOS was constructed. Results 125 IRDEGs were identified, and immune-related pathways included the cytokine-cytokine receptor pathway, T cell receptor signaling pathway, and TNF signaling pathway. All genes were associated with four immune cells (monocyte cells, nTreg, iTreg, and Tcm). Moreover, Major Histocompatibility Complex, Class I, A (HLA-A), Major Histocompatibility Complex, Class I, B (HLA-B), Fos Proto-Oncogene (FOS), Prostaglandin-Endoperoxide Synthase 2 (PTGS2), and C-X-C Motif Chemokine Receptor 4 (CXCR4) were identified as hub genes. Furthermore, N6-Methyladenosine (m6A methylation) mediators could potentially play a pivotal role between the immune system and PCOS. Conclusion This study described the relevance between immune and PCOS. We identified five IRDEGs as hub genes for PCOS. The relationship between the m6A methylation and hub genes indicated that m6A methylation could play a potential role in regulating such hub genes in PCOS. These findings could provide new insights into the molecular mechanisms and diagnosis or treatment strategy for the disease.

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Section: Discussionmentioning

confidence: 99%

Transcriptome Profiling Revealed the Relationship Between Immune-Related Genes and m6A Modifiers in Polycystic Ovary Syndrome

Kong

Zhou

et al. 2022

Preprint

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“…The genes without ensemble gene ID were removed. Next, the results were visualized as volcano plots through the Sangerbox platform 2 ( 24 ). Then, A Venn diagram was created by an online tool 3 to confirm the overlapping DEGs of the two datasets.…”

Section: Methodsmentioning

confidence: 99%

Identification of key interferon-stimulated genes for indicating the condition of patients with systemic lupus erythematosus

et al. 2022

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Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with highly heterogeneous clinical symptoms and severity. There is complex pathogenesis of SLE, one of which is IFNs overproduction and downstream IFN-stimulated genes (ISGs) upregulation. Identifying the key ISGs differentially expressed in peripheral blood mononuclear cells (PBMCs) of patients with SLE and healthy people could help to further understand the role of the IFN pathway in SLE and discover potential diagnostic biomarkers.The differentially expressed ISGs (DEISG) in PBMCs of SLE patients and healthy persons were screened from two datasets of the Gene Expression Omnibus (GEO) database. A total of 67 DEISGs, including 6 long noncoding RNAs (lncRNAs) and 61 messenger RNAs (mRNAs) were identified by the “DESeq2” R package. According to Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, those DEISGs were mainly concentrated in the response to virus and immune system processes. Protein-protein interaction (PPI) network showed that most of these DEISGs could interact strongly with each other. Then, IFIT1, RSAD2, IFIT3, USP18, ISG15, OASL, MX1, OAS2, OAS3, and IFI44 were considered to be hub ISGs in SLE by “MCODE” and “Cytohubba” plugins of Cytoscape, Moreover, the results of expression correlation suggested that 3 lncRNAs (NRIR, FAM225A, and LY6E-DT) were closely related to the IFN pathway.The lncRNA NRIR and mRNAs (RSAD2, USP18, IFI44, and ISG15) were selected as candidate ISGs for verification. RT-qPCR results showed that PBMCs from SLE patients had substantially higher expression levels of 5 ISGs compared to healthy controls (HCs). Additionally, statistical analyses revealed that the expression levels of these ISGs were strongly associated to various clinical symptoms, including thrombocytopenia and facial erythema, as well as laboratory indications, including the white blood cell (WBC) count and levels of autoantibodies. The Receiver Operating Characteristic (ROC) curve demonstrated that the IFI44, USP18, RSAD2, and IFN score had good diagnostic capabilities of SLE.According to our study, SLE was associated with ISGs including NRIR, RSAD2, USP18, IFI44, and ISG15, which may contribute to the future diagnosis and new personalized targeted therapies.

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“…TIMER and TISIDB ( https://cis.hku.hk/TISIDB/index.php ) [ 35 ] are two classic online sites for immunoassays with powerful immune infiltration analyses, which we applied for the evaluation of immune lymphocyte infiltration. Sangerbox ( http://sangerbox.com/Tool ) is a powerful website for raw letter analysis [ 36 ]; this tool used its GO and KEGG analysis functions. The list of extended full names and abbreviations of tumors are provided in Supplementary File 1.…”

Section: Methodsmentioning

confidence: 99%

ATAD2 Upregulation Promotes Tumor Growth and Angiogenesis in Endometrial Cancer and Is Associated with Its Immune Infiltration

et al. 2022

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Background. Endometrial cancer is one of the three major gynecologic malignancies, and its incidence continues to rise. ATPase family AAA structural domain-containing protein 2 (ATAD2) is an ATPase protein, which is an independent factor for poor prognosis in endometrial cancer. However, its role in the disease is yet to be determined. Methods. The Tumor IMmune Estimation Resource (TIMER) database was used to assess ATAD2 expression in pan-cancer, and the relevance of ATAD2 expression in Uterine Corpus Endometrial Carcinoma (UCEC) in clinical settings was obtained using Gene Expression Profiling Interactive Analysis (GEPIA) and UALCAN analysis. In addition, the Human Protein Atlas database was used to assess ATAD2 protein expression in UCEC. Furthermore, in vitro molecular biology and in vivo functional experiments were employed to ascertain the effect of ATAD2 expression on tumor angiogenesis and tumor growth. UALCAN was used to screen for ATAD2 coexpressed genes, and Sangerbox was utilized to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of these coexpressed genes. Finally, the TIMER, Tumor Immune System Interaction and Drug Bank (TISIDB), and GEPIA databases were used to analyze the relationship between ATAD2 and immune infiltration. Results. ATAD2 is highly expressed in a variety of tumors, and in UCEC, it plays the role of a protooncogene. Basic experiments revealed that ATAD2 promotes vascular endothelial growth factor expression in endometrial cancer and affects tumor growth and angiogenesis. In addition, GO and KEGG enrichment analyses showed that ATAD2-associated genes were chiefly enriched in certain signaling pathways, such as herpes simplex virus 1 infection and that ATAD2 was associated with immune infiltration in UCEC. Conclusion. Our findings suggest that ATAD2 promotes tumor growth and angiogenesis in endometrial cancer. Furthermore, ATAD2 is associated with immune infiltration and is a potential diagnostic and therapeutic target.

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Pan-Cancer Analysis Shows That ALKBH5 Is a Potential Prognostic and Immunotherapeutic Biomarker for Multiple Cancer Types Including Gliomas

Cited by 55 publications

References 76 publications

Transcriptome Profiling Revealed the Relationship Between Immune-Related Genes and m6A Modifiers in Polycystic Ovary Syndrome

Transcriptome Profiling Revealed the Relationship Between Immune-Related Genes and m6A Modifiers in Polycystic Ovary Syndrome

Identification of key interferon-stimulated genes for indicating the condition of patients with systemic lupus erythematosus

ATAD2 Upregulation Promotes Tumor Growth and Angiogenesis in Endometrial Cancer and Is Associated with Its Immune Infiltration

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