scholarly journals A Comprehensive Multiomics Analysis Identified Ubiquilin 4 as a Promising Prognostic Biomarker of Immune-Related Therapy in Pan-Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-22
Author(s):  
Jie Li ◽  
Ye Tong ◽  
Zhi Wang ◽  
Yi Liu ◽  
Xiaobo Dai ◽  
...  
Keyword(s):  
Prognostic Biomarker ◽  
Tissue Expression ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Immune Checkpoints ◽  
Human Protein Atlas ◽  
Tumor Mutational Burden ◽  
Number Variation ◽  
Cancer Genome Atlas ◽  
Pan Cancer

Recently, it was reported that ubiquilin 4 (UBQLN4) alteration was associated with genomic instability in some cancers. However, whether UBQLN4 is a valuable biomarker for the prognosis of immunotherapy in pan-cancer was not identified. We evaluated the biologic and oncologic significance of UBQLN4 in pan-cancer at multiomics level, such as expression, mutation, copy number variation (CNV), methylation, and N6-methyladenosine (m6A) methylation. These omics data were obtained from several public databases, including Oncomine, The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), the Genotype-Tissue Expression (GTEx), the Human Protein Atlas (HPA), Gene Set Cancer Analysis (GSCA), m6A-Atlas, CancerSEA, and RNAactDrug. We found that UBQLN4 mRNA and protein were overexpressed in most cancer types, and the expression, mutation, CNV, and methylation of UBQLN4 were associated with the prognosis of some cancers. Mechanistically, UBQLN4 was involved in angiogenesis, DNA damage, apoptosis, and the pathway of PI3K/AKT and TSC/mTOR. Moreover, UBQLN4 mRNA was significantly correlated with immune checkpoints, tumor mutational burden (TMB), microsatellite instability (MSI), and mismatch repair (MMR). And, the correlation among UBQLN4 mRNA, CNV, and methylation and immune microenvironment was also identified. Furthermore, UBQLN4 was associated with the sensitivity of chemotherapy and targeted drugs at multiomics level. In conclusion, UBQLN4 was a promising prognostic biomarker of immune-related therapy in pan-cancer.

scholarly journals ATG101 as a Novel Prognostic Biomarker Related to Immunotherapy in Pan-cancer

2021 ◽  
Author(s):  
Zijian Zhang ◽  
Jinggang Mo ◽  
Chong Jin ◽  
Hao Jiang ◽  
Zhongtao Liu ◽  
...  
Keyword(s):  
Critical Role ◽  
Tissue Expression ◽  
The Cancer Genome Atlas ◽  
Immune Checkpoints ◽  
Integrated Analysis ◽  
Tumour Immunity ◽  
Kaplan Meier ◽  
Cancer Genome Atlas ◽  
The Relationship ◽  
Pan Cancer

Abstract Background: ATG101 plays a significant role in the occurrence and development of tumours by regulating autophagy. Our study aimed to research the correlation between the expression of ATG101 and tumour prognosis and its role in tumour immunity. Methods: First, integrated analysis of The Cancer Genome Atlas and Genotype-Tissue Expression portals were used to analyse the expression of ATG101. Then, we used Kaplan–Meier curves for survival analysis. Next, we analysed the relationship between ATG101 expression and six immune cells, the immune microenvironment and immune checkpoints. Besides, we analysed the relationship between the expression of ATG101 and methyltransferase. Finally, we used GSEA to study the function of ATG101 in COAD and LIHC. Results: Integrated analysis showed that ATG101 was overexpressed in different tumours. Kaplan–Meier curves found that ATG101 was associated with poor prognosis in most tumours. We found that that ATG101 can be used as a target and prognostic marker of tumour immunotherapy for different tumours. We also found that ATG101 regulates DNA methylation. GSEA analysis showed that ATG101 may play a critical role in COAD and LIHC.Conclusions: Our study highlights the significance of ATG101 in the study of tumour immunity from a pan-cancer perspective.

scholarly journals DNASE1L3 as a Novel Diagnostic and Prognostic Biomarker for Lung Adenocarcinoma Based on Data Mining

2021 ◽  
Vol 12 ◽  
Author(s):  
Jianlin Chen ◽  
Junping Ding ◽  
Wenjie Huang ◽  
Lin Sun ◽  
Jinping Chen ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Prognostic Biomarker ◽  
Function Analysis ◽  
Mrna Level ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Immune Checkpoints ◽  
Diagnostic Efficiency ◽  
Protein Levels ◽  
Normal Tissues

Previous researches have highlighted that low-expressing deoxyribonuclease1-like 3 (DNASE1L3) may play a role as a potential prognostic biomarker in several cancers. However, the diagnosis and prognosis roles of DNASE1L3 gene in lung adenocarcinoma (LUAD) remain largely unknown. This research aimed to explore the diagnosis value, prognostic value, and potential oncogenic roles of DNASE1L3 in LUAD. We performed bioinformatics analysis on LUAD datasets downloaded from TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus), and jointly analyzed with various online databases. We found that both the mRNA and protein levels of DNASE1L3 in patients with LUAD were noticeably lower than that in normal tissues. Low DNASE1L3 expression was significantly associated with higher pathological stages, T stages, and poor prognosis in LUAD cohorts. Multivariate analysis revealed that DNASE1L3 was an independent factor affecting overall survival (HR = 0.680, p = 0.027). Moreover, decreased DNASE1L3 showed strong diagnostic efficiency for LUAD. Results indicated that the mRNA level of DNASE1L3 was positively correlated with the infiltration of various immune cells, immune checkpoints in LUAD, especially with some m6A methylation regulators. In addition, enrichment function analysis revealed that the co-expressed genes may participate in the process of intercellular signal transduction and transmission. GSEA indicated that DNASE1L3 was positively related to G protein-coupled receptor ligand biding (NES = 1.738; P adjust = 0.044; FDR = 0.033) and G alpha (i) signaling events (NES = 1.635; P adjust = 0.044; FDR = 0.033). Our results demonstrated that decreased DNASE1L3 may serve as a novel diagnostic and prognostic biomarker associating with immune infiltrates in lung adenocarcinoma.

scholarly journals Downregulated SPINK4 is associated with poor survival in colorectal cancer

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Xiaojie Wang ◽  
Qian Yu ◽  
Waleed M. Ghareeb ◽  
Yiyi Zhang ◽  
Xingrong Lu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Expression Data ◽  
Poor Survival ◽  
Protein Levels ◽  
Normal Tissues ◽  
Human Protein Atlas ◽  
Cancer Genome Atlas ◽  
Independent Indicator

Abstract Background SPINK4 is known as a gastrointestinal peptide in the gastrointestinal tract and is abundantly expressed in human goblet cells. The clinical significance of SPINK4 in colorectal cancer (CRC) is largely unknown. Methods We retrieved the expression data of 1168 CRC patients from 3 Gene Expression Omnibus (GEO) datasets (GSE24551, GSE39582, GSE32323) and The Cancer Genome Atlas (TCGA) to compare the expression level of SPINK4 between CRC tissues and normal colorectal tissues and to evaluate its value in predicting the survival of CRC patients. At the protein level, these results were further confirmed by data mining in the Human Protein Atlas and by immunohistochemical staining of samples from 81 CRC cases in our own center. Results SPINK4 expression was downregulated in CRC compared with that in normal tissues, and decreased SPINK4 expression at both the mRNA and protein levels was associated with poor prognosis in CRC patients from all 3 GEO datasets, the TCGA database and our cohort. Additionally, lower SPINK4 expression was significantly related to higher TNM stage. Moreover, in multivariate regression, SPINK4 was confirmed as an independent indicator of poor survival in CRC patients in all databases and in our own cohort. Conclusions We concluded that reduced expression of SPINK4 relates to poor survival in CRC, functioning as a novel indicator.

scholarly journals Inferring Homologous Recombination Deficiency of Ovarian Cancer From the Landscape of Copy Number Variation at Subchromosomal and Genetic Resolutions

2021 ◽  
Vol 11 ◽  
Author(s):  
Meng Zhang ◽  
Si-Cong Ma ◽  
Jia-Le Tan ◽  
Jian Wang ◽  
Xue Bai ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Homologous Recombination ◽  
Copy Number Variation ◽  
Copy Number ◽  
The Cancer Genome Atlas ◽  
Homologous Recombination Deficiency ◽  
Number Variation ◽  
Cancer Genome Atlas ◽  
Tumor Types ◽  
Pan Cancer

BackgroundHomologous recombination deficiency (HRD) is characterized by overall genomic instability and has emerged as an indispensable therapeutic target across various tumor types, particularly in ovarian cancer (OV). Unfortunately, current detection assays are far from perfect for identifying every HRD patient. The purpose of this study was to infer HRD from the landscape of copy number variation (CNV).MethodsGenome-wide CNV landscape was measured in OV patients from the Australian Ovarian Cancer Study (AOCS) clinical cohort and >10,000 patients across 33 tumor types from The Cancer Genome Atlas (TCGA). HRD-predictive CNVs at subchromosomal resolution were identified through exploratory analysis depicting the CNV landscape of HRD versus non-HRD OV patients and independently validated using TCGA and AOCS cohorts. Gene-level CNVs were further analyzed to explore their potential predictive significance for HRD across tumor types at genetic resolution.ResultsAt subchromosomal resolution, 8q24.2 amplification and 5q13.2 deletion were predominantly witnessed in HRD patients (both p < 0.0001), whereas 19q12 amplification occurred mainly in non-HRD patients (p < 0.0001), compared with their corresponding counterparts within TCGA-OV. The predictive significance of 8q24.2 amplification (p < 0.0001), 5q13.2 deletion (p = 0.0056), and 19q12 amplification (p = 0.0034) was externally validated within AOCS. Remarkably, pan-cancer analysis confirmed a cross-tumor predictive role of 8q24.2 amplification for HRD (p < 0.0001). Further analysis of CNV in 8q24.2 at genetic resolution revealed that amplifications of the oncogenes, MYC (p = 0.0001) and NDRG1 (p = 0.0004), located on this fragment were also associated with HRD in a pan-cancer manner.ConclusionsThe CNV landscape serves as a generalized predictor of HRD in cancer patients not limited to OV. The detection of CNV at subchromosomal or genetic resolution could aid in the personalized treatment of HRD patients.

scholarly journals Pan-cancer survey and evaluation of the oncogenic role of NF-κB1

2021 ◽  
Author(s):  
Lihong Huang ◽  
ruoling zheng ◽  
Huasong Gong ◽  
Yongchao Qiao
Keyword(s):  
Endometrial Carcinoma ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Data Sets ◽  
Carcinogenic Effect ◽  
Uterine Corpus ◽  
T Cell Infiltration ◽  
Cancer Genome Atlas ◽  
Survey And Evaluation ◽  
Pan Cancer

Abstract Although emerging cells or animals based evidence supports an association between nuclear factor kappa-B1 (NF-κB1) cells and cancers, there has no pan-cancer analysis. Therefore, based on TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus) data sets, we first studied the potential carcinogenic effect of NF-κB1 in 33 tumors. As we not only found high expression of NF-κB1 in most tumors, but also found that NF-κB1 expression is closely related to the prognosis of tumor patients. Enhanced phosphorylation of S893 was observed in several tumors, such as breast cancer, uterine corpus endometrial carcinoma or lung adenocarcinoma. In thymoma, NF-κB1 expression was relevant to CD8+ T-cell infiltration levels, and tumor-associated fibroblast infiltration has also seen in other tumors, such as uterine corpus endometrial carcinoma or glioblastoma multiforme. In addition, the functional mechanism of NF-κB1 also involves the related functions of protein processing and RNA metabolism. In this study, NF-κB1 was pan-cancer study in order to have a systematic and comprehensive understanding of the carcinogenic effect of NF-κB1 in different tumors.

scholarly journals Comprehensive Analysis of Immune Correlation of KIF20A in Pan-cancer

2020 ◽  
Author(s):  
Xiao-Han Cui ◽  
Qiu-Ju Peng ◽  
Peng Gao ◽  
Xu-Dong Zhang ◽  
Ren-Zhi Li ◽  
...  
Keyword(s):  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Immune Checkpoints ◽  
Rna Seq ◽  
Gene Set Enrichment ◽  
Related Information ◽  
Common Causes ◽  
Cancer Genome Atlas ◽  
Pan Cancer

Abstract Background: Cancer is one of the most common causes of death, and the morbidity and mortality are gradually increasing in the world. KIF20A plays an important role in tumors, but its immune relevance in pan-cancer needs to be further studied.Methods: KIF20A-related information was download from The Cancer Genome Atlas (TCGA). Collecting RNA-seq data is fragments per kilobase million (FPKM) style data. The ESTIMATE algorithm was used for estimating the stromal and immune scores for 33 tumors. Then, we analyzed the correlation between KIF20A in pan-cancer and immune checkpoints and performed gene set enrichment analysis (GSEA) analysis on the co-expressed genes of KIF20A in pan-cancer.Results: We have confirmed that the expression of KIF20A has a intensive correlation with prognosis in 33 kinds of tumors. Its expression of KIF20A was related to a variety of immune cells and immune checkpoints. Based on the results of GSEA for further analysis, in multiple tumors, KIF20A is related to immune-related pathways.Conclusion: We have demonstrated that KIF20A played an important role in pan-cancer and could affect the occurrence or development of a variety of tumors. Moreover, KIF20A was related to immunity, and KIF20A- related immune research in pan-cancer also needs to be further demonstrate.

Identification of the Expression Signature and Potential Mechanisms of miR-493-3p in NSCLC using Bioinformatics Strategy: A Comprehensive Study from TCGA and GEO Datasets

2020 ◽  
Author(s):  
hongbo zou ◽  
Hong Zou ◽  
Mao Luo ◽  
Qichao Xie ◽  
Lijun Zhong
Keyword(s):  
Target Genes ◽  
Tumor Stage ◽  
Tissue Expression ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Ph Domain ◽  
Hub Genes ◽  
Protein Protein Interaction ◽  
Human Protein Atlas ◽  
Protein Phosphatase 2

Abstract Background Recent evidence highlights that miR-493-3p serve as crucial regulators of tumorigenesis. Nevertheless, the expression and clinical roles of miR-493-3p has been rarely reported in non-small cell lung cancer (NSCLC). Thus, this study was aim to investigate the expression status and potential mechanism of miR-493-3p in NSCLC progression. Methods We initially examined the expression of miR-493-3p in NSCLC through The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) microarrays. The overlap of the conjecture miR-493-3p target genes and down-regulated genes in NSCLC from TCGA were identified as the possible miR-493-3p target genes. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses and protein-protein interaction (PPI) network were constructed to explore the biological function and hub genes of miR-493-3p targets. The expression pattern and prognosis value of key hub genes were examined by Genotype-Tissue Expression (GTEx) database, The Human Protein Atlas and Kaplan- Meier Plotter database. Results miR-493-3p was significantly increased in NSCLC tissues and connected with tumor stage in TCGA and GEO database. A total of 46 genes were identified as miR-493-3p targets, and those involved in various key pathways by GO and KEGG analysis. Furthermore, PH domain and leucine-rich repeat protein phosphatase 2 (PHLPP2) was indicated of miR-493-3p key targets, which low-expressed in NSCLC and predicted better overall survival. Conclusions Our study emphasized that up-regulated miR-493-3p may target PHLLP2 and predicate worse prognosis of NSCLC patients.

scholarly journals Abnormal Expression of NOS3 and Association with Clinical Outcome are Highly Cancer Dependent as Revealed through Pan-Cancer Analysis

2019 ◽  
Author(s):  
Dan Zou ◽  
Fei Lv ◽  
Yi Yang ◽  
Chunjiao Yang ◽  
Yang Chen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cancer Cell Line ◽  
Cancer Therapeutics ◽  
Tissue Expression ◽  
The Cancer Genome Atlas ◽  
Normal Tissues ◽  
Cancer Genome Atlas ◽  
Cancer Tissues ◽  
Oxide Synthase ◽  
Pan Cancer

Abstract Background: NOS3 (endothelial NOS, eNOS) is a member of the nitric oxide synthase (NOS) enzyme family, mainly participating in nitric oxide (NO) generation. NOS3 has been reported to inhibit apoptosis and promote angiogenesis, proliferation, and invasiveness. However, the expression pattern of NOS3 and its diagnostic and prognostic potential has not been investigated in a pan-cancer perspective. Methods: In this research, data from the Genotype-Tissue Expression (GTEx), the Cancer Genome Atlas (TCGA), the Cancer Cell Line Encyclopedia (CCLE) and the Cancer Therapeutics Response Portal (CTRP) were employed and NOS3 expression was comprehensively analysed in normal tissues, cancer tissues and cell lines. Its relationship with clinical phenotypes and drug responses was also analysed. Results: In normal tissues, NOS3 was expressed at the highest levels in the spleen and the lowest levels in the blood. Compared with the corresponding normal tissues, its expression in tumour was significantly increased in seven tumour types but decreased in eight tumour types. And NOS3 expression was positively or negatively related to tumour stage and overall survival of patients depending on the tumour types. The expression of NOS3 was related to the response to ‘SR8278’. Conclusions: NOS3 was differentially expressed in tumour tissues, and had prognosis value in some tumour types. And its correlation to drug response warrants further investigation.

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 Sex, age, tissue, and disease patterns of matrisome expression in GTEx transcriptome data

2021 ◽  
Author(s):  
Tim O. Nieuwenhuis ◽  
Avi Z. Rosenberg ◽  
Matthew N. McCall ◽  
Marc K. Halushka
Keyword(s):  
Gene Expression ◽  
Expression Patterns ◽  
Tissue Expression ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Normal Tissues ◽  
Disease Patterns ◽  
Cancer Genome Atlas ◽  
Unknown Gene ◽  
Gene Expression Levels

AbstractThe extracellular matrix (ECM) has historically been explored through proteomic methods. Whether or not global transcriptomics can yield meaningful information on the human matrisome is unknown. Gene expression data from 17,382 samples across 52 tissues, were obtained from the Genotype-Tissue Expression (GTEx) project. Additional datasets were obtained from The Cancer Genome Atlas (TCGA) program and the Gene Expression Omnibus for comparisons. Gene expression levels generally recapitulated proteome-derived matrisome expression patterns. Further, matrisome gene expression properly clustered tissue types, with some matrisome genes including SERPIN family members having tissue-restricted expression patterns. Deeper analyses revealed 388 genes varied by age and 222 varied by sex in at least one tissue, with expression correlating with digitally imaged histologic tissue features. A comparison of TCGA tumor, TCGA adjacent normal and GTEx normal tissues demonstrated robustness of the GTEx samples as a generalized control, while also determining a common primary tumor matrisome. Additionally, GTEx tissues served as a useful non-diseased control in a separate study of idiopathic pulmonary fibrosis matrix changes. Altogether, these findings indicate that the transcriptome, in general, and GTEx in particular, has value in understanding the state of organ ECM.

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