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 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.

RNF24 is a Novel Biomarker of Prognosis and Immunological Cell Infiltration in Cancers

2021 ◽  
Author(s):  
Bin Yu ◽  
ma mei
Keyword(s):  
Survival Data ◽  
Immune Cell ◽  
Ring Finger ◽  
Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Cell Infiltration ◽  
Pathway Enrichment Analysis ◽  
Systematic Analysis ◽  
Ppi Networks ◽  
Pan Cancer

Abstract Background The RNF family engaged in diverse biological and pathological processes, including tumorigenesis and cancer advance. However, studies about Ring Finger Protein 24 (RNF24) were limited and have not been reported in cancer. A systematic analysis in pan-cancer is a benefit to understand the function of RNF24. Methods RNF24 expression was evaluated in pan-cancer based on the data from The Cancer Genome Atlas (TCGA) analyzed by TIMER, UALCAN, GEPIA, and HPA. Then, the effect of RNF24 on the prognostic value was assessed by clinical survival data in Kaplan–Meier Plotter and GEPIA. And mutation burden and related survival of RNF24 was observed in cBioPortal. Furthermore, protein-protein interaction (PPI) networks of RNF24 and pathway enrichment analysis were explored on multiple websites. Lastly, relationships between RNF24 expression and immune cells infiltration were analyzed in the TIMER2 online database with various algorithms. Results The mRNA and protein levels of RNF24 were significantly upregulated in most types of cancer compared to normal tissues. And RNF24 was a reliable biomarker to predict prognosis in at least 10 types of cancer, including liver hepatocellular carcinoma (LIHC). In addition, we showed the genetic alteration, PPI networks, and functional pathway of RNF24. Moreover, immune cell infiltration exhibited RNF24 expression negatively linked to CD8+ T cells, but positively to Tregs, MDSCs, HSC, and macrophages in pan-cancer.Conclusions Our pan-cancer analysis revealed RNF24 as an oncogene and its expression predicted OS in multiple human cancers, especially in LIHC. RNF24 might predict the immunotherapy response for cancer patients based on its expression with infiltration of immune and immunosuppressive cells.

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 YAP1 is a Prognostic Biomarker and Correlated with Immune Cell Infiltration in Pancreatic Cancer

2021 ◽  
Vol 8 ◽  
Author(s):  
Kai Sun ◽  
Xue-de Zhang ◽  
Xiao-yang Liu ◽  
Pei Lu
Keyword(s):  
Gene Expression ◽  
Pancreatic Cancer ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Prognostic Value ◽  
Immune Cell ◽  
Prognostic Biomarker ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Long Term Outcome

Yes-associated protein-1 (YAP1) is an important effector of the Hippo pathway and has crosstalk with other cancer signaling pathways. It induces an immunosuppressive tumor microenvironment by activating pathways in several cellular components. However, the mechanisms by which it drives immune infiltration in pancreatic cancer remain poorly understood. We analyzed the expression of YAP1 as well as its prognostic value and correlations with immune infiltrates in various cancers, with a focus on pancreatic cancer. In particular, using the Oncomine database and Gene Expression Profiling Interactive Analysis (GEPIA) database, we found that YAP1 is differentially expressed between tumor tissues and control tissues in a number of cancers and in particular, is elevated in pancreatic cancer. Using the Kaplan–Meier plotter, GEPIA, and Long-term Outcome and Gene Expression Profiling database of pan-cancers (LOGpc), we further established the prognostic value of YAP1. We found that YAP1 expression was significantly related to outcomes in multiple types of cancer based on data from The Cancer Genome Atlas, particularly in pancreatic cancer. Correlations between YAP1 and immune cell infiltration and immune cell marker expression were examined using Tumor Immune Estimation Resource and GEPIA. High expression levels of YAP1 were significantly associated with a variety of immune markers and immune cell subsets in pancreatic cancer. These results suggest that YAP1 is correlated with patient outcomes and tumor immune cell infiltration in multiple cancer types and is a valuable prognostic biomarker in pancreatic cancer.

scholarly journals Cancer Stemness Associated With Prognosis and the Efficacy of Immunotherapy in Adrenocortical Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaoxi Shi ◽  
Yuanlin Liu ◽  
Shuai Cheng ◽  
Haidi Hu ◽  
Jian Zhang ◽  
...  
Keyword(s):  
Adrenocortical Carcinoma ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Potential Biomarker ◽  
Lower Expression

BackgroundCancer stem cells (CSCs) have been proven to influence drug resistance, recurrence, and metastasis in tumors. Our study aimed to identify stemness-related prognostic biomarkers for new therapeutic strategies in adrenocortical carcinoma.MethodsRNA-seq data and clinical characteristics were downloaded from The Cancer Genome Atlas (TCGA). The stemness indexes, mDNAsi and mRNAsi, were calculated to classify all samples into low-score and high-score groups. Two algorithms, based on the R language, ESTIMATE and single-sample Gene Set Enrichment Analysis (ssGSEA) were used to assess the immune cell infiltration states of adrenocortical carcinoma patients. Weighted Gene Co-expression Network Analysis (WGCNA) was used to find genes that were related to the stemness of cancer. By bioinformatics methods, the correlations between biomarkers capable of predicting immune checkpoint inhibitors (ICIs) responses and stemness of cancer were explored.ResultsHigh-mRNAsi predicted shorter overall survival (OS) and a higher metastatic trend in adrenocortical carcinoma (ACC) patients. Compared with the low-mRNAsi group, the high-mRNAsi group had a lower ImmuneScore and StromalScroe. Twenty-two stemness-related prognostic genes were obtained by WGCNA, which focused on the function of the cell cycle and cell mitosis. Immune cell infiltration, especially CD8+T cell, increased in the low-mRNAsi group compared with the high-mRNAsi group. Lower expression of PD-L1, CTLA-4, and TIGHT was evaluated in the high-mRNAsi group.ConclusionsACC patients with high-mRNAsi have poor prognosis and less immune cell infiltration. Combined with the finding of lower expression of CTLA-4, TIGHT, and PD-L1 in the high-mRNAsi group, we came to the conclusion that stemness index is a potential biomarker to predict the effectiveness of ICIs.

scholarly journals Dissecting the Role of N6-Methylandenosine-Related Long Non-coding RNAs Signature in Prognosis and Immune Microenvironment of Breast Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Jinguo Zhang ◽  
Benjie Shan ◽  
Lin Lin ◽  
Jie Dong ◽  
Qingqing Sun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Value ◽  
Immune Cell ◽  
Roc Curves ◽  
The Cancer Genome Atlas ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Consensus Clustering ◽  
Prognostic Signature ◽  
Non Coding Rnas

Breast cancer (BC) represents a molecularly and clinically heterogeneous disease. Recent progress in immunotherapy has provided a glimmer of hope for several BC subtypes. The relationship between N6-methyladenosine (m6A) modification and long non-coding RNAs (LncRNAs) is still largely unexplored in BC. Here, with the intention to dissect the landscape of m6A-related lncRNAs and explore the immunotherapeutic value of the m6A-related lncRNA signature, we identified m6A-related lncRNAs by co-expression analysis from The Cancer Genome Atlas (TCGA) and stratified BC patients into different subgroups. Furthermore, we generated an m6A-related lncRNA prognostic signature. Four molecular subtypes were identified by consensus clustering. Cluster 3 preferentially had favorable prognosis, upregulated immune checkpoint expression, and high level of immune cell infiltration. Twenty-one m6A-related lncRNAs were applied to construct the m6A-related lncRNA model (m6A-LncRM). Survival analysis and receiver operating characteristic (ROC) curves further confirmed the prognostic value and prediction performance of m6A-LncRM. Finally, high- and low-risk BC subgroups displayed significantly different clinical features and immune cell infiltration status. Overall, our study systematically explored the prognostic value of the m6A-related LncRNAs and identified a high immunogenicity BC subtype. The proposed m6A-related LncRNA model might serve as a robust prognostic signature and attractive immunotherapeutic targets for BC treatment.

scholarly journals Pan-Cancer Analyses Reveal Oncogenic and Immunological Role of Dickkopf-1 (DKK1)

2021 ◽  
Vol 12 ◽  
Author(s):  
Shuang Gao ◽  
Ye Jin ◽  
Hongmei Zhang
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathway ◽  
Immune Cell ◽  
Wnt Signaling Pathway ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Dickkopf 1 ◽  
Pan Cancer

WNT signaling pathway inhibitor Dickkopf-1 (DKK1) is related to cancer progression; however, its diagnostic and prognostic potential have not been investigated in a pan-cancer perspective. In this study, multiple bioinformatic analyses were conducted to evaluate therapeutic value of DKK1 in human cancers. The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) project served as data resources. The Wilcoxon rank test was performed to evaluate the expression difference of DKK1 between cancer tissues and normal tissues. A Kaplan-Meier curve and Cox regression were used for prognosis evaluation. Single-sample gene set enrichment analysis (ssGSEA) was used to evaluate the association of DKK1 expression with the immune cell infiltration. The potential function of DKK1 was explored by STRING and clusterProfiler. We found that the expression level of DKK1 is significantly different in different cancer types. Importantly, we demonstrated that DKK1 is an independent risk factor in ESCA, LUAD, MESO, and STAD. Further analysis revealed that DKK1 had a large effect on the immune cell infiltration and markers of certain immune cells, such as Th1 and Th2 cells. PPI network analysis and further pathway enrichment analysis indicated that DKK1 was mainly involved in the WNT signaling pathway. Our findings suggested that DKK1 might serve as a marker of prognosis for certain cancers by affecting the WNT signaling pathway and tumor immune microenvironment.

scholarly journals EPDR1 correlates with immune cell infiltration in hepatocellular carcinoma and can be used as a prognostic biomarker

2020 ◽  
Author(s):  
Ruochan Chen ◽  
Yiya Zhang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Functional Analysis ◽  
Immune Cell ◽  
Prognostic Biomarker ◽  
Prognostic Significance ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Normal Tissues

Abstract Background: Hepatocellular carcinoma (HCC) has high mortality rate and is a serious disease burden globally. Hence, identification and characterization of novel biomarkers for the diagnosis and prognosis of HCC are critically important. The protein EPDR1 (ependymin related 1) is a member of piscine brain glycoproteins and is involved in cell adhesion. This is the first study to report the expression of EPDR1 and its prognostic significance, pathological role, and association with cancer immunity in HCC.Methods: The gene expression, prognostic, and clinicopathological analyses were performed based on the data obtained from multiple transcriptome databases. Protein expression of EPDR1 in HCC was verified using human protein atlas and CPTAC databases. Co-expression network analysis using the LinkedOmics database was performed to identify genes co-expressed with EPDR1 expression. Functional analysis of the co-expressed genes, including gene set enrichment analysis was performed to identify the functional role of EPDR1. The statistical analysis was conducted in R, and the relationship between EPDR1 expression and immune cell infiltration was analyzed using TIMER and CIBERSORT resources. Results: The expression of EPDR1 was found to be significantly higher in HCC tissues than in the normal tissues and is an independent prognostic factor for the overall survival of HCC patients. Further, a high level of EPDR1 was shown to be correlated with advanced stage of HCC. Functional analysis revealed that EPDR1 is associated with multiple signaling pathways as well as pathways related to cancer and apoptosis. Notably, EPDR1 expression significantly correlated with purity and the infiltration levels of B cells, CD8+ and CD4+ T cells, macrophages, neutrophils, and dendritic cells in HCC. Further, the EPDR1 expression significantly correlated with the expression of immune signatures, such as KIR2DL4, ITGAM, GATA3, STAT6, STAT5A, BCL6, STAT3, and HAVCR2.Conclusions: Our study identified EPDR1 as a novel prognostic biomarker in HCC. The expression of EPDR1 was shown to be associated with immune cell infiltration as well as the signature molecules that potentially regulate these processes during the carcinogenesis of HCC. With better understanding of its biological function, EPDR1 could become an effective target for HCC diagnosis and treatment in the future.

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.

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