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

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.

scholarly journals Identifying and characterizing lincRNA genomic clusters reveals its cooperative functions in human cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Hanxiao Zhou ◽  
Yue Gao ◽  
Xin Li ◽  
Shipeng Shang ◽  
Peng Wang ◽  
...  
Keyword(s):  
Human Cancer ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Computational Method ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Pathophysiological Mechanism ◽  
Multiple Cancer ◽  
Cancer Types ◽  
Genomic Clusters

Abstract Background Emerging evidence has revealed that some long intergenic non-coding RNAs (lincRNAs) are likely to form clusters on the same chromosome, and lincRNA genomic clusters might play critical roles in the pathophysiological mechanism. However, the comprehensive investigation of lincRNA clustering is rarely studied, particularly the characterization of their functional significance across different cancer types. Methods In this study, we firstly constructed a computational method basing a sliding window approach for systematically identifying lincRNA genomic clusters. We then dissected these lincRNA genomic clusters to identify common characteristics in cooperative expression, conservation among divergent species, targeted miRNAs, and CNV frequency. Next, we performed comprehensive analyses in differentially-expressed patterns and overall survival outcomes for patients from The Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx) across multiple cancer types. Finally, we explored the underlying mechanisms of lincRNA genomic clusters by functional enrichment analysis, pathway analysis, and drug-target interaction. Results We identified lincRNA genomic clusters according to the algorithm. Clustering lincRNAs tended to be co-expressed, highly conserved, targeted by more miRNAs, and with similar deletion and duplication frequency, suggesting that lincRNA genomic clusters may exert their effects by acting in combination. We further systematically explored conserved and cancer-specific lincRNA genomic clusters, indicating they were involved in some important mechanisms of disease occurrence through diverse approaches. Furthermore, lincRNA genomic clusters can serve as biomarkers with potential clinical significance and involve in specific pathological processes in the development of cancer. Moreover, a lincRNA genomic cluster named Cluster127 in DLK1-DIO3 imprinted locus was discovered, which contained MEG3, MEG8, MEG9, MIR381HG, LINC02285, AL132709.5, and AL132709.1. Further analysis indicated that Cluster127 may have the potential for predicting prognosis in cancer and could play their roles by participating in the regulation of PI3K-AKT signaling pathway. Conclusions Clarification of the lincRNA genomic clusters specific roles in human cancers could be beneficial for understanding the molecular pathogenesis of different cancer types.

scholarly journals Characteristics of the Immune Cell Infiltration Landscape in Gastric Cancer to Assistant Immunotherapy

2022 ◽  
Vol 12 ◽  
Author(s):  
Chenlu Li ◽  
Jingjing Pan ◽  
Yinyan Jiang ◽  
Yan Yu ◽  
Zhenlin Jin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Signaling Pathways ◽  
Poor Prognosis ◽  
Immune Cell ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Therapeutic Responses

Background: Gastric cancer (GC) was usually associated with poor prognosis and invalid therapeutical response to immunotherapy due to biological heterogeneity. It is urgent to screen reliable indices especially immunotherapy-associated parameters that can predict the therapeutic responses to immunotherapy of GC patients.Methods: Gene expression profile of 854 GC patients were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets (GSE84433) with their corresponding clinical and somatic mutation data. Based on immune cell infiltration (ICI) levels, molecular clustering classification was performed to identify subtypes and ICI scores in GC patients. After functional enrichment analysis of subtypes, we further explored the correlation between ICI scores and Tumor Mutation Burden (TMB) and the significance in clinical immunotherapy response.Results: Three subtypes were identified based on ICI scores with distinct immunological and prognostic characteristics. The ICI-cluster C, associated with better outcomes, was characterized by significantly higher stromal and immune scores, T lymphocytes infiltration and up-regulation of PD-L1. ICI scores were identified through using principal component analysis (PCA) and the low ICI scores were consistent with the increased TMB and the immune-activating signaling pathways. Contrarily, the high-ICI score cluster was involved in the immunosuppressive pathways, such as TGF-beta, MAPK and WNT signaling pathways, which might be responsible for poor prognosis of GC. External immunotherapy and chemotherapy cohorts validated the patients with lower ICI scores exhibited significant therapeutic responses and clinical benefits.Conclusion: This study elucidated that ICI score could sever as an effective prognostic and predictive indicator for immunotherapy in GC. These findings indicated that the systematic assessment of tumor ICI landscapes and identification of ICI scores have crucial clinical implications and facilitate tailoring optimal immunotherapeutic strategies.

scholarly journals P4HA1, a Prognostic Biomarker that Correlates With Immune Infiltrates in Lung Adenocarcinoma and Pan-Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Qi Zhao ◽  
Junfeng Liu
Keyword(s):  
Prognostic Value ◽  
Immune Cell ◽  
Prognostic Biomarker ◽  
Enrichment Analysis ◽  
Tissue Expression ◽  
The Cancer Genome Atlas ◽  
Cell Infiltration ◽  
Pathway Enrichment Analysis ◽  
Immune Cell Infiltration ◽  
Pan Cancer

Objective: Prolyl 4-hydroxylase, alpha polypeptide I (P4HA1), a key enzyme in collagen synthesis, comprises two identical alpha subunits and two beta subunits. However, the immunomodulatory role of P4HA1 in tumor immune microenvironment (TIME) remains unclear. This study aimed to evaluate the prognostic value of P4HA1 in pan-cancer and explore the relationship between P4HA1 expression and TIME.Methods: P4HA1 expression, clinical features, mutations, DNA methylation, copy number alteration, and prognostic value in pan-cancer were investigated using the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression data. Pathway enrichment analysis of P4HA1 was performed using R package “clusterProfiler.” The correlation between immune cell infiltration level and P4HA1 expression was analyzed using three sources of immune cell infiltration data, including ImmuCellAI database, TIMER2 database, and a published work.Results: P4HA1 was substantially overexpressed in most cancer types. P4HA1 overexpression was associated with poor survival in patients. Additionally, we discovered that P4HA1 expression was positively associated with infiltration levels of immunosuppressive cells, such as tumor-associated macrophages, cancer-associated fibroblasts, nTregs, and iTregs, and negatively correlated with CD8+ T and NK cells in pan-cancer.Conclusions: Our results highlighted that P4HA1 might serve as a potential prognostic biomarker in pan-cancer. P4HA1 overexpression is indicative of an immunosuppressive microenvironment. P4HA1 may be a potential target of immunotherapy.

scholarly journals HILPDA Is a Prognostic Biomarker and Correlates With Macrophage Infiltration in Pan-Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Chengdong Liu ◽  
Xiaohan Zhou ◽  
Hanyi Zeng ◽  
Dehua Wu ◽  
Li Liu
Keyword(s):  
Survival Data ◽  
Immune Cell ◽  
Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Clinical Prognosis ◽  
Cancer Data ◽  
Tumor Types ◽  
Pan Cancer

Background: The protein hypoxia-inducible lipid droplet-associated (HILPDA) is differentially expressed in various tumors. However, its role and correlation with immune cell infiltration in most tumors remain unclear.Methods: HILPDA expression was analyzed in pan-cancer data from The Cancer Genome Atlas (TCGA) database. The influence of HILPDA in clinical prognosis was evaluated using clinical survival data from TCGA. Enrichment analysis of HILPDA was conducted using the R package “clusterProfiler.” We downloaded the immune cell infiltration score of TCGA samples from published articles and analyzed the correlation between the magnitude of immune cell infiltration and HILPDA expression.Results: HILPDA was highly expressed and associated with worse overall survival, disease-specific survival, and progression-free interval in most tumor types. In addition, HILPDA expression was significantly associated with the glycolysis pathway and infiltration of immune cells. Tumor-associated macrophage (TAM) infiltration increased in tissues with high HILPDA expression in most tumor types. Immunosuppressive genes, such as PD-L1, PD-1, TGFB1, and TGFBR1 were positively correlated with HILPDA.Conclusions: Our study suggests that HILPDA is a marker of poor prognosis. High HILPDA may contribute to TAM infiltration and be associated with tumor immunosuppression status.

scholarly journals ARNTL2, an Immunoregulation-Related Prognostic Biomarker in Pan-Cancer and Lung Adenocarcinoma

2021 ◽  
Author(s):  
Gujie Wu ◽  
Wenmiao Wang ◽  
Zheng Yang ◽  
Qun Xue
Keyword(s):  
Lung Adenocarcinoma ◽  
Immune Cell ◽  
Prognostic Biomarker ◽  
The Cancer Genome Atlas ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Cancer Drugs ◽  
Anti Cancer ◽  
Pan Cancer

Abstract Background ARNTL2 is a member of the PAS superfamily that promotes tumor progression. However, the role of ARNTL2 in lung adenocarcinoma (LUAD) remains unclear. The purpose of our study was to investigate the function of ARNTL2 in LUAD. Methods The expression, clinical features, and prognostic role of ARNTL2 in pan-cancer were evaluated using The Cancer Genome Atlas and Genotype-Tissue Expression data. GSEA and GSVA of ARNTL2 were performed using the R package “clusterProfiler.” The correlation between immune cell infiltration level and ARNTL2 expression was analyzed using two sources of immune cell infiltration data, including the TIMER2 and ImmuCellAI database. Finally,we analyzed the correlation between ARNTL2 and IC50 of 192 drugs. Results ARNTL2 was substantially overexpressed in LUAD and pan-cancer. High ARNTL2 expression predicted poor survival in patients with LUAD. We also found that ARNTL2 expression was positively associated with the infiltration levels of immunosuppressive cells, such as tumor associated macrophages, cancer associated fibroblasts and Tregs. Among the 192 anti-cancer drugs, ARNTL2 expression was positively correlated with IC50 of 114 anti-cancer drugs, such as SB505124, Doramapimod, Nutlin-3a (-), Sabutoclax, AZD5991, PF-4708671, Elephantin, PRIMA-1MET, Sorafenib, Vorinostat, and MK-2206. Conclusions Our results revealed that ARNTL2 is a potential prognostic biomarker in LUAD. An elevated ARNTL2 expression indicates an immunosuppressive microenvironment, and targeted therapies against ARNTL2 have excellent potential.

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

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.

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

2021 ◽  
Author(s):  
Kuangxun Li ◽  
Junzhe Liu ◽  
Xinyu Yang ◽  
Zewei Tu ◽  
Kai Huang ◽  
...  
Keyword(s):  
Immune Cell ◽  
Expression Profiles ◽  
Immune Therapy ◽  
Gene Expression Pattern ◽  
Expression Level ◽  
Cell Infiltration ◽  
Clinical Samples ◽  
Immune Cell Infiltration ◽  
Cancer Types ◽  
Pan Cancer

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.

scholarly journals AHSA1 is a Prognostic Biomarker that Correlates with Macrophage Infiltration in Pan-Cancer

2021 ◽  
Author(s):  
Fulei Li ◽  
Chengdong Liu ◽  
Yanling Chen ◽  
Shasha Li ◽  
Lu Bai
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Immune Cell ◽  
Enrichment Analysis ◽  
Tissue Expression ◽  
The Cancer Genome Atlas ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Cancer Data ◽  
Pan Cancer

Abstract Background: Activator of heat shock 90 kDa protein ATPase homolog 1 (AHSA1) is differentially expressed in several tumor types. However, its association with immune cell infiltration remains elusive. Methods: AHSA1 expression was analyzed using The Cancer Genome Atlas (TCGA) pan-cancer data and normal tissue expression data from Genotype-Tissue Expression (GTEx). The clinical prognostic role of AHSA1 in pan-cancer was investigated, and an enrichment analysis of AHSA1 was performed using the R package “clusterProfiler.” We downloaded data regarding the immune cell infiltration level of TCGA pan-cancer tissues and analyzed the association between immune cell infiltration and AHSA1 expression. Results: The results of TCGA pan-cancer data analysis revealed that AHSA1 was overexpressed and associated with poor survival in patients with cancer. Furthermore, the infiltration levels of tumor-associated macrophages (TAMs) were higher, while those of CD8+ T cells were lower, in the high AHSA1 expression group. Conclusions: Our study suggests that AHSA1 is an oncogene and a risk factor for patient survival in cancer. AHSA1 may contribute to high infiltration levels of TAMs and low infiltration levels of CD8+ T cells, thus indicating that high AHSA1 expression may be associated with the tumor immunosuppressive microenvironment.

scholarly journals Pan-Cancer Analysis of PIMREG as a Biomarker for the Prognostic and Immunological Role

2021 ◽  
Vol 12 ◽  
Author(s):  
Hua Zhu ◽  
Xinyao Hu ◽  
Yingze Ye ◽  
Zhihong Jian ◽  
Yi Zhong ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Chemokine Receptors ◽  
Antigen Processing ◽  
Immune Cell ◽  
Nk Cell ◽  
Cell Lineage ◽  
Cell Receptor ◽  
The Cancer Genome Atlas ◽  
Cancer Types ◽  
Pan Cancer

Phosphatidylinositol binding clathrin assembly protein interacting mitotic regulator (PIMREG) localizes to the nucleus and can significantly elevate the nuclear localization of clathrin assembly lymphomedullary leukocythemia gene. Although there is some evidence to support an important action for PIMREG in the occurrence and development of certain cancers, currently no pan-cancer analysis of PIMREG is available. Therefore, we intended to estimate the prognostic predictive value of PIMREG and to explore its potential immune function in 33 cancer types. By using a series of bioinformatics approaches, we extracted and analyzed datasets from Oncomine, The Cancer Genome Atlas, Cancer Cell Lineage Encyclopedia (CCLE) and the Human Protein Atlas (HPA), to explore the underlying carcinogenesis of PIMREG, including relevance of PIMREG to prognosis, microsatellite instability (MSI), tumor mutation burden (TMB), tumor microenvironment (TME) and infiltration of immune cells in various types of cancer. Our findings indicate that PIMREG is highly expressed in at least 24 types of cancer, and is negatively correlated with prognosis in major cancer types. In addition, PIMREG expression was correlated with TMB in 24 cancers and with MSI in 10 cancers. We revealed that PIMREG is co-expressed with genes encoding major histocompatibility complex, immune activation, immune suppression, chemokine and chemokine receptors. We also found that the different roles of PIMREG in the infiltration of different immune cell types in different tumors. PIMREG can potentially influence the etiology or pathogenesis of cancer by acting on immune-related pathways, chemokine signaling pathway, regulation of autophagy, RIG-I like receptor signaling pathway, antigen processing and presentation, FC epsilon RI pathway, complement and coagulation cascades, T cell receptor pathway, NK cell mediated cytotoxicity and other immune-related pathways. Our study suggests that PIMREG can be applied as a prognostic marker in a variety of malignancies because of its role in tumorigenesis and immune infiltration.

scholarly journals Glucose-6-Phosphate Dehydrogenase is a Prognostic Biomarker and Correlated with Immune Infiltrates in Hepatocellular Carcinoma

2022 ◽  
Author(s):  
Yang Bu ◽  
Kejun Liu ◽  
Yiming Niu ◽  
Ji Hao ◽  
Lei Cui ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Microenvironment ◽  
Liver Cancer ◽  
Immune Cell ◽  
Cox Regression ◽  
Functional Enrichment ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Potential Biomarker ◽  
Glucose 6 Phosphate Dehydrogenase

Abstract Background: Glucose-6-phosphate dehydrogenase (G6PD) plays an important role in the metabolic and immunological aspects of tumors. In hepatocellular carcinoma (HCC), the alteration of tumor microenvironment influences recurrence and metastasis. We extracted G6PD-related data from public databases of HCC tissues and used a bioinformatics approach to explore the correlation between G6PD expression and clinicopathological features and prognosis of immune cell infiltration in HCC.Methods: We extract G6PD expression information from TCGA and GEO databases in liver cancer tissues and normal tissues, validated by immunohistochemistry, and the correlation between G6PD expression and clinical features is analyzed, and the clinical significance of G6PD in liver cancer is assessed by Kaplan-Meier, Cox regression and prognostic line graph models. Functional enrichment analysis is performed by protein-protein interaction (PPI) network, GO/KEGG, GSEA and G6PD-associated differentially expressed genes (DEGs). TIMER and ssGSEA packages are used to assess the correlation between expression and the level of immune cell infiltration.Results: Our results show that G6PD expression is significantly upregulated in hepatocellular carcinoma tissues (P < 0.001). G6PD expression is associated with histological grade, pathological stage, T-stage, vascular infiltration and AFP level (P < 0.05); HCC patients in the low G6PD expression group had longer overall survival and better prognosis compared with the high G6PD expression group (P < 0.05). The level of G6PD expression also affects the levels of macrophages, unactivated dendritic cells, B cells, and follicular helper T cells in the tumor microenvironment.Conclusion: High expression of G6PD is a potential biomarker for poor prognosis of hepatocellular carcinoma, and G6PD may be a target for immunotherapy of HCC.

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