Pan-cancer analysis of N4-acetylcytidine adaptor THUMPD1 as a predictor for prognosis and immunotherapy

Background: THUMPD1 is a specific RNA adaptor that assists acetylation of mRNA and production of N4-acetylcytidine (ac4C). However, it remains unclear whether THUMPD1 plays a part in tumorigenesis and therapeutic efficacy. Here, we analyzed the expression profiles and prognostic value of THUMPD1 in pan-cancer and gained insights into the correlation between THUMPD1 expression level and immunotherapy efficacy. Methods: Gene expression pattern and its correlation with prognosis, immune cell infiltration in pan-cancer were obtained from GTEx, CCLE and TCGA databases, with Kaplan-Meier method and Spearman correlation analysis used. Western blotting and immunofluorescence on clinical samples was performed to validate our database-derived results. Correlation between THUMPD1 expression level and immunotherapy responses was also explored, based on clinical cohorts receiving PD-L1 antibody therapy. Finally, GSEA was performed to show the possible tumorigenic mechanism. Results: THUMPD1 was highly expressed in most cancer types, and this elevated expression indicated poor or improved prognosis for different cancers. In kidney renal clear cell carcinoma (KIRC) and rectum adenocarcinoma (READ), patients with higher THUMPD1 expression exhibited a better prognosis, while liver hepatocellular carcinoma (LIHC) patients had worse prognosis. Besides, THUMPD1 was significantly associated with immune cell infiltration, tumor mutation burden (TMB), microsatellite instability (MSI)，immune checkpoints and neoantigen in many cancer types. Further, more clinical advantages and therapeutic responses were observed in patients with high THUMPD1 expression. Conclusions: THUMPD1 may serve as a novel predictor to evaluate cancer prognosis and immune therapy efficacy in diverse cancer types.

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Prognostic and Immunological Characterization of NSD3 Evaluated through an Integrative Pan-Cancer Analysis

10.21203/rs.3.rs-591803/v1 ◽

2021 ◽

Author(s):

Sha Li ◽

Yaqiong Liu ◽

Chaoling Yao ◽

Anji Xu ◽

Xiaoling Zeng ◽

...

Keyword(s):

Immune Cell ◽

Human Cancer ◽

The Cancer Genome Atlas ◽

Functional Enrichment ◽

Cell Infiltration ◽

Immune Cell Infiltration ◽

Multiple Cancer ◽

Cancer Dataset ◽

Cancer Types ◽

Pan Cancer

Abstract Background: Nuclear receptor binding SET domain protein-3 (NSD3) has been reported to be a crucial regulator of carcinogenesis as a histone lysine methyltransferase in multiple cancer types. However, the underlying mechanisms have not been clearly delineated. Therefore, we aimed to investigate the expression pattern, prognostic value, and potential function of NSD3 in 33 types of human cancer. Methods: The potential roles of NSD3 were explored using datasets from The Cancer Genome Atlas (TCGA) pan-cancer dataset and an array of bioinformatics methods, including analyses of the relationship between NSD3 expression and prognosis, tumor mutational burden (TMB), microsatellite instability (MSI), DNA amplification, and immune cell inﬁltration across 33 cancer types. Results: Many types of cancers are characterized according to the dysregulation of NSD3, which is associated with the pathological stage of cancer. Patients in our study with higher NDS3 levels, which were attributed to NSD3 copy number amplification, always experienced shorter survival periods. Additionally, NSD3 expression was associated with TMB and MSI in 10 different cancer types. The top five cancers whose NSD3 expression correlated with immune scores were further analyzed. The levels of immune-cell infiltration differed significantly between high and low NSD3-expressing samples in each of the five cancer types. Functional enrichment of the NSD3 co-expressed genes indicated a role for NSD3 in the regulation of immune responses and tumorigenesis. Conclusions: Our study revealed that NSD3 can function as a prognostic marker in various cancers due to its role in tumorigenesis and tumor immunity.

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Pan-Cancer Analysis of the Associations of TGFBI Expression With Prognosis and Immune Characteristics

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.745649 ◽

2021 ◽

Vol 8 ◽

Author(s):

Yun Chen ◽

Han Zhao ◽

Yao Feng ◽

Qin Ye ◽

Jing Hu ◽

...

Keyword(s):

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Immune Cell ◽

Cell Infiltration ◽

Immune Cell Infiltration ◽

Tumor Mutational Burden ◽

Mrna And Protein Expression ◽

Cancer Types ◽

Growth Factor Beta ◽

Pan Cancer

Transforming growth factor-beta-induced (TGFBI) protein has important roles in tumor growth, metastasis, and immunity. However, there is currently no pan-cancer evidence regarding TGFBI. In this study, we conducted a pan-cancer analysis of TGFBI mRNA and protein expression and prognoses of various cancer types using public databases. We also investigated the associations of TGFBI expression with tumor microenvironment (TME) components, immune cell infiltration, tumor mutational burden (TMB), and microsatellite instability (MSI), along with the TGFBI genetic alteration types. The results showed that TGFBI expression varied among different cancer types, and it was positively or negatively related to prognosis in various cancers. TGFBI expression was also significantly correlated with TME components, TMB, MSI, immune cell infiltration, and immunoinhibitory and immunostimulatory gene subsets. These findings indicate that TGFBI participates in various immune responses and it may function as a prognostic marker in various cancers. The findings may be useful for developing immunotherapies that target TGFBI.

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Identification of key biomarkers and immune infiltration in systemic lupus erythematosus by integrated bioinformatics analysis

Journal of Translational Medicine ◽

10.1186/s12967-020-02698-x ◽

2021 ◽

Vol 19 (1) ◽

Cited By ~ 1

Author(s):

Xingwang Zhao ◽

Longlong Zhang ◽

Juan Wang ◽

Min Zhang ◽

Zhiqiang Song ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Immune Cell ◽

Expression Profiles ◽

Gene Set Enrichment Analysis ◽

Cell Infiltration ◽

Immune Cell Infiltration ◽

Tissue Destruction ◽

Systemic Lupus ◽

Ppi Networks

Abstract Background Systemic lupus erythematosus (SLE) is a multisystemic, chronic inflammatory disease characterized by destructive systemic organ involvement, which could cause the decreased functional capacity, increased morbidity and mortality. Previous studies show that SLE is characterized by autoimmune, inflammatory processes, and tissue destruction. Some seriously-ill patients could develop into lupus nephritis. However, the cause and underlying molecular events of SLE needs to be further resolved. Methods The expression profiles of GSE144390, GSE4588, GSE50772 and GSE81622 were downloaded from the Gene Expression Omnibus (GEO) database to obtain differentially expressed genes (DEGs) between SLE and healthy samples. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments of DEGs were performed by metascape etc. online analyses. The protein–protein interaction (PPI) networks of the DEGs were constructed by GENEMANIA software. We performed Gene Set Enrichment Analysis (GSEA) to further understand the functions of the hub gene, Weighted gene co‐expression network analysis (WGCNA) would be utilized to build a gene co‐expression network, and the most significant module and hub genes was identified. CIBERSORT tools have facilitated the analysis of immune cell infiltration patterns of diseases. The receiver operating characteristic (ROC) analyses were conducted to explore the value of DEGs for SLE diagnosis. Results In total, 6 DEGs (IFI27, IFI44, IFI44L, IFI6, EPSTI1 and OAS1) were screened, Biological functions analysis identified key related pathways, gene modules and co‐expression networks in SLE. IFI27 may be closely correlated with the occurrence of SLE. We found that an increased infiltration of moncytes, while NK cells resting infiltrated less may be related to the occurrence of SLE. Conclusion IFI27 may be closely related pathogenesis of SLE, and represents a new candidate molecular marker of the occurrence and progression of SLE. Moreover immune cell infiltration plays important role in the progession of SLE.

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Immune cell infiltration characteristics and related core genes in lupus nephritis: results from bioinformatic analysis

10.21203/rs.2.12276/v1 ◽

2019 ◽

Author(s):

Yiling Cao ◽

Weihao Tang ◽

Wanxin Tang

Keyword(s):

Gene Expression ◽

Lupus Nephritis ◽

Molecular Mechanisms ◽

Immune Cell ◽

Expression Profiles ◽

Gene Set Enrichment Analysis ◽

Cell Infiltration ◽

Immune Cell Infiltration ◽

Spearman Correlation ◽

Core Genes

Abstract Objects Lupus nephritis (LN) is a common complication of systemic lupus erythematosus that presents a high risk of end-stage renal disease. In the present study, we used CIBERSORT and gene set enrichment analysis (GSEA) of gene expression profiles to identify immune cell infiltration characteristics and related core genes in LN. Methods Datasets from the Gene Expression Omnibus, GSE32591 and GSE113342, were downloaded for further analysis. The GSE32591 dataset, which included 32 LN glomerular biopsy tissues and 14 glomerular tissues of living donors, was analyzed by CIBERSORT. Different immune cell types in LN were analyzed by the Limma software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis based on GSEA were performed by clusterProfiler software. Lists of core genes were derived from Spearman correlation between the most significant GO term and differentially expressed immune cell gene from CIBERSORT. GSE113342 was employed to validate the association between selected core genes and clinical manifestation. Result Five types of immune cells revealed important associations with LN, and monocytes emerged to be the prominent differences. GO and KEGG analyses indicated that immune response pathways are significantly enriched in LN. The Spearman correlation indicated that 15 genes, including FCER1G, CLEC7A, MARCO, CLEC7A, PSMB9, and PSMB8, were closely related to clinical features. Conclusion This study is the first to identify immune cell infiltration with microarray data of glomeruli in LN by using CIBERSORT analysis and provides novel evidence and clues for further research of the molecular mechanisms of LN.

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Comprehensive Analysis of YTH Domain Family in Lung Adenocarcinoma: Expression Profile, Association with Prognostic Value, and Immune Infiltration

Disease Markers ◽

10.1155/2021/2789481 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Kuan Hu ◽

Lei Yao ◽

Yuanliang Yan ◽

Lei Zhou ◽

Juanni Li

Keyword(s):

T Cells ◽

Lung Adenocarcinoma ◽

Prognostic Value ◽

Immune Cell ◽

Expression Profiles ◽

Family Members ◽

Cell Infiltration ◽

Immune Cell Infiltration ◽

Domain Family ◽

Yth Domain

Background. All YTH domain family members are m6A reader proteins accounting for the methylation modulation involved in the process of tumorgenesis and tumor progression. However, the expression profiles and roles of the YTH domain family in lung adenocarcinoma (LUAD) remain to be further illustrated. Methods. GEPIA2 and TNMplot databases were used to generate the expression profiles of the YTH family. Kaplan-Meier plotter database was employed to analysis the prognostic value of the YTH family. Coexpression profiles and genetic alterations analysis of the YTH family were undertaken using the cBioPortal database. YTH family protein-associated protein-protein interaction (PPI) network was identified by using STRING. Functional enrichment analysis was performed with the help of the WebGestalt database. The correlation analysis between the YTH family and immune cell infiltration in LUAD was administrated by using the TIMER2.0 database. Results. mRNA expression of YTHDC1 and YTHDC2 was significantly lower in LUAD, whereas YTHDF1, YTHDF2, and YTHDF3 with apparently higher expression. YTHDF2 expression was observed to be the highest in the nonsmoker subgroup, and its expression gradually decreased with the increased severity of smoking habit. LUAD patients with low expression of YTHDC2, YTHDF1, and YTHDF2 were correlated with a better overall survival (OS) time. The YTHDF1 genetic alteration rate was 26%, which was the highest in the YTH family. The major cancer-associated functions of YTH family pointed in the direction of immunomodulation, especially antigen processing and presentation. Most of the YTH family members were significantly correlated with the infiltration of CD4+ T cells, CD8+ T cells, macrophages, and neutrophils, indicating the deep involvement of the YTH domain family in the immune cell infiltration in LUAD. Conclusion. The molecular and expression profiles of the YTH family were dysregulated in LUAD. YTH family members (especially YTHDC2) were promising biomarkers and potential therapeutic targets that may bring benefit for the patients with LUAD.

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Identification of gene expression profiles and immune cell infiltration signatures between low and high tumor mutation burden groups in bladder cancer

International Journal of Medical Sciences ◽

10.7150/ijms.39056 ◽

2020 ◽

Vol 17 (1) ◽

pp. 89-96 ◽

Cited By ~ 3

Author(s):

Zonglong Wu ◽

Muru Wang ◽

Qinggang Liu ◽

Yaxiao Liu ◽

Kejia Zhu ◽

...

Keyword(s):

Gene Expression ◽

Bladder Cancer ◽

Immune Cell ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Cell Infiltration ◽

Immune Cell Infiltration ◽

Tumor Mutation Burden ◽

Mutation Burden

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Gene Signatures and Cancer-Immune Phenotypes Based on m6A Regulators in Breast Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.756412 ◽

2021 ◽

Vol 11 ◽

Author(s):

Guanghui Zhao ◽

Junhua An ◽

Qian Pu ◽

Wenwen Geng ◽

Haiyun Song ◽

...

Keyword(s):

Breast Cancer ◽

Immune Cell ◽

The Cancer Genome Atlas ◽

Cell Infiltration ◽

Clinical Samples ◽

Immune Cell Infiltration ◽

Breast Cancer Patients ◽

Gene Signatures ◽

Immune Phenotypes ◽

Processing Stability

The N6-methyladenosine (m6A) has been considered as a new layer of epitranscriptomic regulation on mRNA processing, stability, and translation. However, potential roles of m6A RNA methylation modification in tumor immune microenvironment (TIME) of breast cancer are yet fully understood. In this study, we comprehensively evaluated the genetic variations and transcript expressions of 15 m6A regulators in 1,079 breast cancer samples from the Cancer Genome Atlas (TCGA) database. We validated major regulators had significantly differential mRNA and protein expression in tumor tissue compared to normal tissues from 39 pairs of clinical breast cancer samples with different molecular subtypes, and especially high expression of m6A readers YTHDF1 and YTHDF3 predicted poor survival. Two clusters of breast cancer patients identified by the 15 m6A regulators’ pattern showed distinct overall survival, immune activation status, and immune cell infiltration, and clinical samples confirmed the diversity of lymphocytic infiltration. The profiles of these two clusters accorded with that of two classical cancer-immune phenotypes, immune-excluded and immune-inflamed phenotypes, it suggested that m6A regulators-based patterns might serve as crucial mediators of TIME in breast cancer. Moreover, the m6A phenotype-related gene signatures could also be survival predictor in breast cancer. Therefore, comprehensive evaluation of tumor m6A modification pattern will contribute to enhance our understanding of the characterization of immune cell infiltration in the tumor microenvironment and promote the responsiveness of breast cancer to immunotherapy.

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Landscape of Immune Cell Infiltration in Cervical Cancer

10.21203/rs.3.rs-584271/v1 ◽

2021 ◽

Author(s):

Shasha Shi ◽

Fu Peng ◽

Chenghao Yu

Keyword(s):

Cervical Cancer ◽

Immune Cell ◽

Checkpoint Inhibitors ◽

Expression Profiles ◽

The United States ◽

The Cancer Genome Atlas ◽

Cell Infiltration ◽

Immune Checkpoints ◽

Immune Cell Infiltration ◽

Cancer Tissues

Abstract BackgroundCervical cancer is a life-threatening cancer among women. It is the second most prevalent malignant tumor in women. It ranks high in cancer deaths among women worldwide, including in the United States. Immune checkpoint inhibitors have emerged as an important therapeutic approach to treat several cancers, including cervical cancer. Notably, the development and progress of cervical cancer may be related to sustained immune response. This underlines the need to clarify immune cell infiltration (ICI) in cervical cancer tissues. MethodsIn this study, disease-related information of 964 cervical cancer patients was first retrieved from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database. We utilized bioinformatics data to analyze the expression profiles of immune genes in cervical cancer tissues. ResultsPatients were divided into high and low groups according to ICI score. High ICI scores corresponded with activation of immune signaling pathways and high tumor mutation burden (TMB), which was related to better prognosis of G1-2 cervical cancer. In addition, most immune checkpoints and immuno-related genes such as CD274, CD8A, CXCL10, etc. were over-expressed in the high ICI group. ConclusionsThis study demonstrated that ICI score can accurately predict the prognosis of cervical cancer. Understanding ICI patterns will deepen our understanding of tumor microenvironment (TME) of cervical cancer, which may create the foundation for the development of efficient immunotherapeutic strategies against the cancer.

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