scholarly journals A Pan-Cancer Analysis of the Oncogenic and Immunogenic Role of m6Am Methyltransferase PCIF1

2021 ◽  
Vol 11 ◽  
Author(s):  
Ming-Zhu Jin ◽  
Yi-Gan Zhang ◽  
Wei-Lin Jin ◽  
Xi-Peng Wang
Keyword(s):  
T Cells ◽  
Disease Free Survival ◽  
Renal Clear Cell Carcinoma ◽  
Cancer Prognosis ◽  
Myeloid Dendritic Cells ◽  
Normal Tissues ◽  
T Cell Infiltration ◽  
Initial Stage ◽  
Tumor Mutational Burden ◽  
Pan Cancer

BackgroundPhosphorylated CTD-interacting factor 1 (PCIF1) is identified as the only known methyltransferase of N6,2′-O-dimethyladenosine (m6Am) in mRNA. However, its oncogenic and immunogenic role in cancer research is at an initial stage.MethodsHerein, we carried out a pan-cancer analysis of PCIF1, with a series of datasets (e.g., TIMER2.0, GEPIA2, cBioPortal).ResultsPCIF1 expression was higher in most cancers than normal tissues and was discrepant across pathological stages. Highly expressed PCIF1 was positively correlated with overall survival (OS) or disease-free survival (DFS) of some tumors. PCIF1 expression had a positive correlation with CD4+ T-cell infiltration in kidney renal clear cell carcinoma (KIRC), CD8+ T cells, macrophages, and B cells in thyroid carcinoma (THCA), and immune checkpoint genes (ICGs) in LIHC but a negative correlation with CD4+ T cells, neutrophils, myeloid dendritic cells, and ICGs in THCA. It also affected tumor mutational burden (TMB) and microsatellite instability (MSI) of most tumors.ConclusionPCIF1 expression was correlated with cancer prognosis and immune infiltration, suggesting it to be a potential target for cancer therapy.

scholarly journals CDCA3 Is a Novel Prognostic Biomarker Associated with Immune Infiltration in Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Zhihuai Wang ◽  
Shuai Chen ◽  
Gaochao Wang ◽  
Sun Li ◽  
Xihu Qin
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Immune Cell ◽  
Disease Free Survival ◽  
In Silico Analysis ◽  
Gene Markers ◽  
Free Survival ◽  
Immune Infiltration ◽  
Normal Tissues ◽  
Tumor Tissues

Cell division cycle-associated protein-3 (CDCA3) contributes to the regulation of the cell cycle. CDCA3 plays an important role in the carcinogenesis of various cancers; however, the association between CDCA3 expression, prognosis of patients, and immune infiltration in the tumor microenvironment is still unknown. Here, we demonstrated that CDCA3 was differentially expressed between the tumor tissues and corresponding normal tissues using in silico analysis in the ONCOMINE and Tumor Immune Estimation Resource (TIMER) databases. We analyzed the relationship between the expression of CDCA3 and prognosis of patients with hepatocellular carcinoma (HCC) using the Kaplan–Meier plotter database and Gene Expression Profiling Interactive Analysis (GEPIA). Furthermore, we determined the prognostic value of CDCA3 expression using univariate and multivariate analyses. We observed that CDCA3 expression closely correlated with immune infiltration and gene markers of infiltrating immune cells in the TIMER database. CDCA3 was highly expressed in the tumor tissues than in the adjacent normal tissues in various cancers, including HCC. Increased expression of CDCA3 was accompanied by poorer overall survival (OS), relapse-free survival (RFS), progression-free survival (PFS), and disease-specific survival (DSS). The correlation between CDCA3 expression and OS and disease-free survival (DFS) was also studied using GEPIA. CDCA3 expression was associated with the levels of immune cell infiltration and was positively correlated with tumor purity. Moreover, CDCA3 expression was associated with gene markers such as PD-1, CTLA4, LAG3, and TIM-3 from exhausted T cells, CD3D, CD3E, and CD2 from T cells, and TGFB1 and CCR8 located on the surface of Tregs. Thus, we demonstrated that CDCA3 may be a potential target and biomarker for the management and diagnosis of HCC.

scholarly journals Prognostic and Immunological Role of mRNA ac4C Regulator NAT10 in Pan-Cancer: New Territory for Cancer Research?

2021 ◽  
Vol 11 ◽  
Author(s):  
Chuanxi Yang ◽  
Tingting Wu ◽  
Jing Zhang ◽  
Jinhui Liu ◽  
Kun Zhao ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Carcinoma ◽  
Marker Gene ◽  
Gene Marker ◽  
Immune Infiltration ◽  
Normal Tissues ◽  
Kaplan Meier ◽  
Positive Correlations ◽  
Liver Hepatocellular Carcinoma ◽  
Pan Cancer

BackgroundNAT10 (also known as human N-acetyltransferase-like protein) is a critical gene that regulates N4-acetylcytidine formation in RNA, similar to the multiple regulators of N6-methyladenosine. However, the underlying functions and mechanisms of NAT10 in tumor progression and immunology are unclear.MethodsIn this study, we systematically analyzed the pan-cancer expression and correlations of NAT10, using databases including Oncomine, PrognoScan, GEPIA2, and Kaplan-Meier Plotter. The potential correlations of NAT10 with immune infiltration stages and gene marker sets were analyzed using the Tumor Immune Estimation Resource and GEPIA2.ResultsCompared with normal tissues, NAT10 showed higher expression in most cancers based on combined data from TCGA and GTEx. In different datasets, high NAT10 expression was significantly correlated with poor prognosis in adrenocortical carcinoma, head and neck squamous cell carcinoma, liver hepatocellular carcinoma, kidney renal papillary cell carcinoma, and pheochromocytoma and paraganglioma. Moreover, there were significant positive correlations between NAT10 expression and immune infiltrates, including B cells, CD8+ T cells, CD4+ T cells, neutrophils, macrophages, dendritic cells, endothelial cells, and fibroblasts in LIHC. NAT10 expression showed strong correlations with diverse immune marker gene sets in LIHC.ConclusionNAT10 expression affects the prognosis of pan-cancer patients and is significantly correlated with tumor immune infiltration. Furthermore, it represents a potential target for cancer therapy.

scholarly journals Prognostic and Immunological Role of mRNA ac4C Regulator NAT10 in Pan-Cancer: New Territory for Cancer Research?

2020 ◽  
Author(s):  
Chuanxi Yang ◽  
Tingting Wu ◽  
Jing Zhang ◽  
Jinghui Liu ◽  
Kun Zhao ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Carcinoma ◽  
Marker Gene ◽  
Gene Marker ◽  
Immune Infiltration ◽  
Normal Tissues ◽  
Kaplan Meier ◽  
Positive Correlations ◽  
Liver Hepatocellular Carcinoma ◽  
Pan Cancer

Abstract BackgroundNAT10 (also known as human N-acetyltransferase-like protein) is a critical gene that regulates N4-acetylcytidine formation in RNA, similar to the multiple regulators of N6-methyladenosine. However, the underlying functions and mechanisms of NAT10 in tumor progression and immunology are unclear.MethodsIn this study, we systematically analyzed the pan-cancer expression and correlations of NAT10, using databases including Oncomine, PrognoScan, GEPIA, and Kaplan-Meier Plotter. The potential correlations of NAT10 with immune infiltration stages and gene marker sets were analyzed using the Tumor Immune Estimation Resource and GEPIA.ResultsCompared with normal tissues, NAT10 showed higher expression in 26 of 27 cancers based on combined data from TCGA and GTEx. In different datasets, high NAT10 expression was significantly correlated with poor prognosis in adrenocortical carcinoma, head and neck squamous cell carcinoma, liver hepatocellular carcinoma, kidney renal papillary cell carcinoma, and pheochromocytoma and paraganglioma. Moreover, there were significant positive correlations between NAT10 expression and immune infiltrates, including B cells, CD8+ T cells, CD4+ T cells, neutrophils, macrophages, dendritic cells, endothelial cells, and fibroblasts in LIHC. NAT10 expression showed strong correlations with diverse immune marker gene sets in LIHC.ConclusionNAT10 expression affects the prognosis of pan-cancer patients and is significantly correlated with tumor immune infiltration. Furthermore, it represents a potential target for cancer therapy.

scholarly journals Expression signature, prognosis value, and immune characteristics of MUC1 identified by pan-cancer analysis

2021 ◽  
Author(s):  
Zi-Jian Zhang ◽  
YunPeng Huang ◽  
Zhong-Tao Liu ◽  
Kai Liu ◽  
Yong-Xiang Wang ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Immune Checkpoint ◽  
Disease Free Survival ◽  
Spearman Correlation ◽  
Free Survival ◽  
Spearman Correlation Test ◽  
The Relationship ◽  
Pan Cancer ◽  
Disease Free

Abstract Background: Mucin 1 (MUC1) plays a major role in the occurrence and development of tumor by regulating the process of tumor cell proliferation, epithelial-mesenchymal transformation and epigenetics. However, the relationship between MUC1 expression and tumor prognosis and its role in tumor immunity is still worth exploring. Methods: MUC1 expression was analyzed via GTEx database and TCGA database. We used the Kaplan-Meier survival estimation method to evaluate the influence of MUC1 on tumor prognosis through the survival information from TGCA database. The correlations between MUC1 and immune cell infiltration, tumor microenvironment were investigated through TIMER algorithm and ESTIMATE. In addition, we used Spearman correlation test to examine the correlation between MUC1 and TMB, MSI. Spearman correlation test was also designed to predict the correlation between MUC1 and immune checkpoint genes, four methyltransferases. Further, Gene Set Enrichment Analysis was used to explore the potential mechanism of MUC1 in Adrenocortical carcinoma (ACC) and Liver hepatocellular carcinoma (LIHC). Results: Our study reported that MUC1 is highly expressed in most tumors, differing between cancer types. In most cancers, high expression of MUC1 means poor prognosis indicators, such as overall survival (OS), disease free survival (DSS), disease free survival (DFS) and progression free survival (PFS). MUC1 was positively correlated with infiltrating levels of B cells, CD4+ T cells and CD8+ T cells, dendritic cells, macrophages, neutrophils in LIHC, Prostate adenocarcinoma (PRAD) and Thyroid carcinoma (THCA). Besides, we reported that the expression of MUC1 correlated significantly with immune checkpoint gene, TMB and MSI and in most tumors. However, we found that MUC1 is negatively correlated with most immunotherapy-related indicators in BRCA and LUAD. The relationship between MUC1 and tumor neoantigens and DNA methylase is different in different tumors.In ACC and LIHC, MUC1 can promote the metabolism of many substances. MUC1 can inhibit amyotrophic lateral sclerosis, DNA replication, base excision repair, proteasome in ACC. Similarly, MUC1 inhibits axon guidance, the interaction of cytokine and cytokine receptor, focal adhesion, and endocytosis in LIHC. Conclusions: Our research demonstrates that MUC1 is correlated with prognosis and tumor-infiltrating immune cells, including those of B cells, CD8+ T cells, CD4+ T cells, dendritic cells, macrophages, neutrophils in different tumors. In addition, MUC1 is related to immune checkpoint gene, neoantigen, and some prognostic indicators of immunotherapy such as TMB and MSI, suggesting that MUC1 can also be invoked as a target and prognostic biomarker of immunotherapy. By analyzing the relationship between the expression of MUC1 and methyltransferase, we found that MUC1 regulates DNA methylation. Finally, we used GSEA to study the function of MUC1 in ACC and LIHC. Briefly, our study highlights the significance of MUC1 in the study of tumor immunity from the perspective of pan-cancer.

scholarly journals The bioinformatics and experimental analysis of AlkB family for prognosis and immune cell infiltration in hepatocellular carcinoma

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12123
Author(s):  
Bi Peng ◽  
Yuanliang Yan ◽  
Zhijie Xu
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Metal Ion ◽  
Immune Cell ◽  
Disease Free Survival ◽  
Normal Liver ◽  
Expression Levels ◽  
Normal Tissues ◽  
Molecular Profiles

Background Serving as N6-methyladenosine demethylases, the AlkB family is involved in the tumorigenesis of hepatocellular carcinoma (HCC). However, the molecular profiles and clinical values of the AlkB family in HCC are not well known. Methods Several bioinformatics tools and in vitro experiments were used to identify the immune-related profiles and prognostic values of AlkB family in HCC. Results In this study expression levels of ALKBH1/2/3/4/7 were all remarkably increased in HCC tissues when compared with normal tissues. Quantitative PCR (qPCR) and immunohistochemistry were used to validate the expression of AlkB family members in HCC tissues and normal liver tissues. In addition, high expression levels of ALKBH4 were negatively correlated with overall survival (OS) and disease-free survival (DFS) in patients with HCC. Increased ALKBH4 was also associated with pathological stage in HCC patients. The molecular profiles of AlkB family in HCC were mainly associated with peptidyl-serine modification, peptidyl-tyrosine modification, regulation of metal ion transport, etc. Furthermore, tumor-infiltrating immune cell analysis indicated that ALKBH1/2/3/4/5/6/7/8 and FTO were related to the infiltration of different immune cell, such as CD8+ T cells, macrophages, neutrophils, dendritic cells and CD4+ T cells. We also discovered that the methylation levels of ALKBH1/2/4/5/6/8 and FTO were remarkably reduced in HCC tissues. Conclusions Collectively, our findings may deepen the understanding of specific molecular profiles of the AlkB family in HCC pathology. In particular, ALKBH4 could serve as a promising prognostic candidate for treating HCC, and these results might potentiate the development of more reliable therapeutic strategies for patients with HCC.

scholarly journals Deep analysis of neuroblastoma core regulatory circuitries using online databases and integrated bioinformatics shows their pan-cancer roles as prognostic predictors

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Leila Jahangiri ◽  
Perla Pucci ◽  
Tala Ishola ◽  
Joao Pereira ◽  
Megan L. Cavanagh ◽  
...  
Keyword(s):  
Overall Survival ◽  
Patient Survival ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Deep Understanding ◽  
Risk Groups ◽  
Tumour Microenvironment ◽  
Cancer Prognosis ◽  
Human Pathology ◽  
Pan Cancer

Abstract Aim Neuroblastoma is a heterogeneous childhood cancer derived from the neural crest. The dual cell identities of neuroblastoma include Mesenchymal (MES) and Adrenergic (ADRN). These identities are conferred by a small set of tightly-regulated transcription factors (TFs) binding super enhancers, collectively forming core regulatory circuitries (CRCs). The purpose of this study was to gain a deep understanding of the role of MES and ADRN TFs in neuroblastoma and other cancers as potential indicators of disease prognosis, progression, and relapse. Methods To that end, we first investigated the expression and mutational profile of MES and ADRN TFs in neuroblastoma. Moreover, we established their correlation with neuroblastoma risk groups and overall survival while establishing their extended networks with long non-coding RNAs (lncRNAs). Furthermore, we analysed the pan-cancer expression and mutational profile of these TFs and their correlation with patient survival and finally their network connectivity, using a panel of bioinformatic tools including GEPIA2, human pathology atlas, TIMER2, Omicsnet, and Cytoscape. Results We show the association of multiple MES and ADRN TFs with neuroblastoma risk groups and overall survival and find significantly higher expression of various MES and ADRN TFs compared to normal tissues and their association with overall survival and disease-free survival in multiple cancers. Moreover, we report the strong correlation of the expression of these TFs with the infiltration of stromal and immune cells in the tumour microenvironment and with stemness and metastasis-related genes. Furthermore, we reveal extended pan-cancer networks comprising these TFs that influence the tumour microenvironment and metastasis and may be useful indicators of cancer prognosis and patient survival. Conclusion Our meta-analysis shows the significance of MES and ADRN TFs as indicators of patient prognosis and the putative utility of these TFs as potential novel biomarkers.

FADS1 is a Prognostic Biomarker in Bladder Cancer: A Study Based on TCGA Data

2020 ◽  
Vol 23 ◽  
Author(s):  
Ying Lu ◽  
Jing Shao ◽  
Xu Shu ◽  
Yaofei Jiang ◽  
Jianfang Rong ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Histological Grade ◽  
Clinical Stage ◽  
Fatty Acid Desaturase ◽  
Clinical Information ◽  
The Cancer Genome Atlas ◽  
Cancer Prognosis ◽  
Normal Tissues ◽  
Potential Biomarker ◽  
T Classification

Aim and Objective: Fatty acid desaturase 1 (FADS1) has been reported to be a potential biomarker in various cancers. However, no study has explored the relationship between FADS1 expression and bladder cancer. Our study aimed to investigate the role of FADS1 in bladder cancer prognosis via The Cancer Genome Atlas (TCGA). Materials and Methods: RNA-Seq expression of 414 tumor tissues and 19 paired normal tissues, as well as corresponding clinical data, were downloaded from TCGA database. Two cancer cases were excluded due to a lack of clinical information. The association between FADS1 and the clinicopathological features of bladder cancer was analyzed. This study was conducted in October of 2019 in China. Results: The high expression of FADS1 in bladder cancer was significantly related to histological grade (OR = 0.155 for low vs. high), clinical stage (OR=2.074 for III or IV vs. I or II), T classification (OR=2.326 for T3 or T4 vs. T1 or T2), lymphatic metastasis (OR=1.923 for N1 or N2 or N3 vs. N0) and distant metastasis (OR=4.883 for yes vs. no) (all p-values <0.05). Bladder cancer with high FADS1 levels was related to a worse prognosis than bladder cancer with low FADS1 levels (p= 1.626*10-5 ), according to median expression value 3.622. FADS1 was an independent factor of overall survival in bladder cancer, with a hazard ratio of 1.048 (95%CI: 1.020–1.077, p = 0.001). Conclusions: Increased FADS1 expression in bladder cancer is associated with advanced clinical pathological features and may be a potential biomarker for poor prognosis.

Bioinformatics Analysis Identifies CPZ as a Tumor Immunology Biomarker For Gastric Cancer

2020 ◽  
Vol 15 ◽  
Author(s):  
Yuan Gu ◽  
Ying Gao ◽  
Xiaodan Tang ◽  
Huizhong Xia ◽  
Kunhe Shi
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
Signaling Pathway ◽  
Tumor Immunology ◽  
Bioinformatics Analysis ◽  
Human Cancer ◽  
Disease Free Survival ◽  
Kaplan Meier ◽  
Potential Biomarker ◽  
Pathway Regulation

Background: Gastric cancer (GC) is one of the most common malignancies worldwide. However, the biomarkers for the prognosis and diagnosis of Gastric cancer were still need. Objective: The present study aimed to evaluate whether CPZ could be a potential biomarker for GC. Method: Kaplan-Meier plotter (http://kmplot.com/analysis/) was used to determine the correlation between CPZ expression and overall survival (OS) and disease-free survival (DFS) time in GC [9]. We analyzed CPZ expression in different types of cancer and the correlation of CPZ expression with the abundance of immune infiltrates, including B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells, via gene modules using TIMER Database. Results: The present study identified that CPZ was overexpressed in multiple types of human cancer, including Gastric cancer. We found that overexpression of CPZ correlates to the poor prognosis of patients with STAD. Furthermore, our analyses show that immune infiltration levels and diverse immune marker sets are correlated with levels of CPZ expression in STAD. Bioinformatics analysis revealed that CPZ was involved in regulating multiple pathways, including PI3K-Akt signaling pathway, cGMP-PKG signaling pathway, Rap1 signaling pathway, TGF-beta signaling pathway, regulation of cell adhesion, extracellular matrix organization, collagen fibril organization, collagen catabolic process. Conclusion: This study for the first time provides useful information to understand the potential roles of CPZ in tumor immunology and validate it to be a potential biomarker for GC.

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