scholarly journals Prognostic Value and Immune Characteristics of RUNX Family in Human Cancers: A Pan-cancer Analysis

2021 ◽  
Author(s):  
Han Zhao ◽  
Yun Chen ◽  
Peijun Shen ◽  
Lan Gong
Keyword(s):  
Gene Expression ◽  
Gene Family ◽  
Immune Cell ◽  
Malignant Tumors ◽  
Genetic Alterations ◽  
Genetic Mutation ◽  
The Cancer Genome Atlas ◽  
Different Types ◽  
Cancer Types ◽  
Pan Cancer

Abstract Background: Runt‑related transcription factors (RUNX) are involved in numerous fundamental biological processes and play crucial parts in tumorigenesis and metastasis both directly and indirectly. However, the pan-cancer evidence of RUNX gene family is no available. Methods: In this study, we analyzed the potential association between RUNX gene family expression and patient’s prognosis, immune cell infiltration, drug response, and genetic mutation data across different types of tumors using based on The Cancer Genome Atlas, Gene Expression Omnibus, and Oncomine database. Results: The results showed that the expression of the RUNX family varied among different cancer types, revealing its heterogeneity in cancers, and that expression of RUNX2 was lower than that of RUNX1 and RUNX3 across all cancer types. RUNX family gene expression was related to prognosis in several cancers. Furthermore, our study revealed a clear association between RUNX family expression and ESTIMATE score, RNA stemness, and DNA stemness scores. Compared with RUNX1 and RUNX2, RUNX3 showed relatively low levels of genetic alterations. RUNX family genes had clear associations with immune infiltrate subtypes, and their expression was positively related to immune checkpoint genes and drug sensitivity in most cases. Conclusions: These findings will help to elucidate the potential oncogenic roles of RUNX family genes in different types of cancer and it can function as a prognostic marker in various malignant tumors.

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 Integrative Analysis Reveals Comprehensive Altered Metabolic Genes Linking with Tumor Epigenetics Modification in Pan-Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Yahui Shi ◽  
Jinfen Wei ◽  
Zixi Chen ◽  
Yuchen Yuan ◽  
Xingsong Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Histone Acetylation ◽  
Epigenetic Modification ◽  
Metabolic Reprogramming ◽  
The Cancer Genome Atlas ◽  
Altered Expression ◽  
Metabolic Genes ◽  
Cancer Types ◽  
Pan Cancer

Background. Cancer cells undergo various rewiring of metabolism and dysfunction of epigenetic modification to support their biosynthetic needs. Although the major features of metabolic reprogramming have been elucidated, the global metabolic genes linking epigenetics were overlooked in pan-cancer. Objectives. Identifying the critical metabolic signatures with differential expressions which contributes to the epigenetic alternations across cancer types is an urgent issue for providing the potential targets for cancer therapy. Method. The differential gene expression and DNA methylation were analyzed by using the 5726 samples data from the Cancer Genome Atlas (TCGA). Results. Firstly, we analyzed the differential expression of metabolic genes and found that cancer underwent overall metabolism reprogramming, which exhibited a similar expression trend with the data from the Gene Expression Omnibus (GEO) database. Secondly, the regulatory network of histone acetylation and DNA methylation according to altered expression of metabolism genes was summarized in our results. Then, the survival analysis showed that high expression of DNMT3B had a poorer overall survival in 5 cancer types. Integrative altered methylation and expression revealed specific genes influenced by DNMT3B through DNA methylation across cancers. These genes do not overlap across various cancer types and are involved in different function annotations depending on the tissues, which indicated DNMT3B might influence DNA methylation in tissue specificity. Conclusions. Our research clarifies some key metabolic genes, ACLY, SLC2A1, KAT2A, and DNMT3B, which are most disordered and indirectly contribute to the dysfunction of histone acetylation and DNA methylation in cancer. We also found some potential genes in different cancer types influenced by DNMT3B. Our study highlights possible epigenetic disorders resulting from the deregulation of metabolic genes in pan-cancer and provides potential therapy in the clinical treatment of human cancer.

scholarly journals Systematic Pan-Cancer Analysis Identifies TREM2 as an Immunological and Prognostic Biomarker

2021 ◽  
Vol 12 ◽  
Author(s):  
Xin Cheng ◽  
Xiaowei Wang ◽  
Kechao Nie ◽  
Lin Cheng ◽  
Zheyu Zhang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Immune Cell ◽  
Lung Squamous Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
Immunoglobulin Superfamily ◽  
Cancer Types ◽  
Pan Cancer

Triggering receptor expressed on myeloid cells-2 (TREM2) is a transmembrane receptor of the immunoglobulin superfamily and a crucial signaling hub for multiple pathological pathways that mediate immunity. Although increasing evidence supports a vital role for TREM2 in tumorigenesis of some cancers, no systematic pan-cancer analysis of TREM2 is available. Thus, we aimed to explore the prognostic value, and investigate the potential immunological functions, of TREM2 across 33 cancer types. Based on datasets from The Cancer Genome Atlas, and the Cancer Cell Line Encyclopedia, Genotype Tissue-Expression, cBioPortal, and Human Protein Atlas, we employed an array of bioinformatics methods to explore the potential oncogenic roles of TREM2, including analyzing the relationship between TREM2 and prognosis, tumor mutational burden (TMB), microsatellite instability (MSI), DNA methylation, and immune cell infiltration of different tumors. The results show that TREM2 is highly expressed in most cancers, but present at low levels in lung cancer. Further, TREM2 is positively or negatively associated with prognosis in different cancers. Additionally, TREM2 expression was associated with TMB and MSI in 12 cancer types, while in 20 types of cancer, there was a correlation between TREM2 expression and DNA methylation. Six tumors, including breast invasive carcinoma, cervical squamous cell carcinoma and endocervical adenocarcinoma, kidney renal clear cell carcinoma, lung squamous cell carcinoma, skin cutaneous melanoma, and stomach adenocarcinoma, were screened out for further study, which demonstrated that TREM2 gene expression was negatively correlated with infiltration levels of most immune cells, but positively correlated with infiltration levels of M1 and M2 macrophages. Moreover, correlation with TREM2 expression differed according to T cell subtype. Our study reveals that TREM2 can function as a prognostic marker in various malignant tumors because of its role in tumorigenesis and tumor immunity.

scholarly journals Pan-cancer driver copy number alterations identified by joint expression/CNA data analysis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Gaojianyong Wang ◽  
Dimitris Anastassiou
Keyword(s):  
Gene Expression ◽  
Copy Number ◽  
The Cancer Genome Atlas ◽  
Copy Number Alterations ◽  
Multiple Cancer ◽  
Cancer Driver ◽  
Large Gene ◽  
Cancer Genome Atlas ◽  
Cancer Types ◽  
Pan Cancer

Abstract Analysis of large gene expression datasets from biopsies of cancer patients can identify co-expression signatures representing particular biomolecular events in cancer. Some of these signatures involve genomically co-localized genes resulting from the presence of copy number alterations (CNAs), for which analysis of the expression of the underlying genes provides valuable information about their combined role as oncogenes or tumor suppressor genes. Here we focus on the discovery and interpretation of such signatures that are present in multiple cancer types due to driver amplifications and deletions in particular regions of the genome after doing a comprehensive analysis combining both gene expression and CNA data from The Cancer Genome Atlas.

scholarly journals Effect of LAMA4 on Prognosis and Its Correlation with Immune Infiltration in Gastric Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Mingming Wang ◽  
Changzheng Li ◽  
Ying Liu ◽  
Zuomin Wang
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Immune Cell ◽  
Expression Patterns ◽  
Disease Free Survival ◽  
Genetic Alterations ◽  
Clinicopathological Characteristics ◽  
Basement Membranes ◽  
The Cancer Genome Atlas ◽  
Receptor Interaction

Background. Laminin alpha 4 (LAMA4) is widely distributed in the basement membranes of various tissues. It can regulate cancer cell proliferation and migration. We investigated the effects of LAMA4 in gastric cancer (GC). Methods. LAMA4 expression patterns were analyzed in GC using the Gene Expression Omnibus (GEO), Gene Expression Profiling Interactive Analysis (GEPIA), and UALCAN. Correlations between LAMA4 expression and clinicopathological characteristics were evaluated using data from The Cancer Genome Atlas (TCGA). The survival analysis was examined using the Kaplan-Meier plotter and GEPIA and ascertained by multivariate Cox analysis. Genetic alterations and DNA methylation of LAMA4 were analyzed using cBioPortal and MethSurv. LinkedOmics was applied to identify coexpressed genes of LAMA4. The association between LAMA4 and infiltration of immune cells was explored using Tumor Immune Estimation Resource (TIMER) and GEPIA. Results. LAMA4 was highly expressed in GC, and its upregulation significantly correlated with T classification ( P = 0.040 ). LAMA4 expression was an independent risk factor for overall survival (OS, P = 0.033 ). Patients with genetic alterations of LAMA4 showed a significantly better disease-free survival (DFS, P = 0.022 ). Ten CpG sites of LAMA4 were significantly associated with prognosis in GC. The functions of LAMA4 and coexpression genes were mainly involved in extracellular matrix (ECM) receptor interaction. LAMA4 expression significantly correlated with infiltration of macrophages ( P < 0.001 ), CD4+ T cells ( P < 0.001 ), and dendritic cells ( P < 0.001 ). Furthermore, LAMA4 expression was significantly associated with markers of M2 and tumor-associated macrophages (TAMs). Conclusion. LAMA4 expression was linked to GC prognosis and immune cell infiltration, indicating its potential use as a prognostic biomarker and therapeutic target.

scholarly journals Glutamine Metabolism Regulators Associated with Cancer Development and the Tumor Microenvironment: A Pan-Cancer Multi-Omics Analysis

Genes ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1305
Author(s):  
Jingwen Zou ◽  
Kunpeng Du ◽  
Shaohua Li ◽  
Lianghe Lu ◽  
Jie Mei ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tumor Microenvironment ◽  
Drug Sensitivity ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Metabolic Reprogramming ◽  
Glutamine Metabolism ◽  
Molecular Networks ◽  
Cancer Types ◽  
Pan Cancer

Background: In recent years, metabolic reprogramming has been identified as a hallmark of cancer. Accumulating evidence suggests that glutamine metabolism plays a crucial role in oncogenesis and the tumor microenvironment. In this study, we aimed to perform a systematic and comprehensive analysis of six key metabolic node genes involved in the dynamic regulation of glutamine metabolism (referred to as GLNM regulators) across 33 types of cancer. Methods: We analyzed the gene expression, epigenetic regulation, and genomic alterations of six key GLNM regulators, including SLC1A5, SLC7A5, SLC3A2, SLC7A11, GLS, and GLS2, in pan-cancer using several open-source platforms and databases. Additionally, we investigated the impacts of these gene expression changes on clinical outcomes, drug sensitivity, and the tumor microenvironment. We also attempted to investigate the upstream microRNA–mRNA molecular networks and the downstream signaling pathways involved in order to uncover the potential molecular mechanisms behind metabolic reprogramming. Results: We found that the expression levels of GLNM regulators varied across cancer types and were related to several genomic and immunological characteristics. While the immune scores were generally lower in the tumors with higher gene expression, the types of immune cell infiltration showed significantly different correlations among cancer types, dividing them into two clusters. Furthermore, we showed that elevated GLNM regulators expression was associated with poor overall survival in the majority of cancer types. Lastly, the expression of GLNM regulators was significantly associated with PD-L1 expression and drug sensitivity. Conclusions: The elevated expression of GLNM regulators was associated with poorer cancer prognoses and a cold tumor microenvironment, providing novel insights into cancer treatment and possibly offering alternative options for the treatment of clinically refractory cancers.

scholarly journals FAM65A as a novel prognostic biomarker in human tumors reveal by a pan-cancer analysis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Wenken Liang ◽  
Chune Mo ◽  
Jianfen Wei ◽  
Wei Chen ◽  
Weiwei Gong ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Biomarker ◽  
Malignant Tumors ◽  
Sequence Similarity ◽  
Human Tumor ◽  
Colon Adenocarcinoma ◽  
Human Tumors ◽  
The Cancer Genome Atlas ◽  
Different Types ◽  
Pan Cancer

Abstract Background Family with sequence similarity 65 member A (FAM65A), also known as RIPOR1, is differentially expressed between human tumor and non-tumor tissues in kinds of cancers. In addition, it was reported that the product of FAM65A may be a biomarker for cholangiocarcinoma patients. However, there is still no evidence on the relationship between the FAM65A and different types of tumors. Our study is mainly for exploring the prognostic values of FAM65A in pan-cancer and for further discovering a potential therapeutics target. Methods We analyzed FAM65A expression, prognostic values, genetic alteration, protein phosphorylation, immune infiltration and enrichment analysis across different types of human malignant tumors based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Additionally, Real-Time PCR (RT-qPCR) was performed to further confirm the roles of FAM65A in the pathogenesis of colorectal cancer. Results We found that FAM65A expression was associated with the prognosis of multiple human tumors, especially colorectal cancer. Moreover, we also observed that FAM65A was highly expressed in colorectal cancer through RT-qPCR. We observed that decreasing phosphorylation level of the S351 locus in colon adenocarcinoma, uterine corpus endometrial carcinoma and lung adenocarcinoma. And the expression of FAM65A was positively related to cancer-associated fibroblasts (CAFs) infiltration in many tumors, such as colon adenocarcinoma. Therefore, FAM65A may be a potential prognostic biomarker of human tumors.

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 Pan-Cancer Genome-Wide DNA Methylation Analyses Revealed That Hypermethylation Influences 3D Architecture and Gene Expression Dysregulation in HOXA Locus During Carcinogenesis of Cancers

2021 ◽  
Vol 9 ◽  
Author(s):  
Gang Liu ◽  
Zhenhao Liu ◽  
Xiaomeng Sun ◽  
Xiaoqiong Xia ◽  
Yunhe Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Cell Lines ◽  
Dna Interaction ◽  
Gene Expression Omnibus ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Topological Domains ◽  
Cancer Types ◽  
Pan Cancer

DNA methylation dysregulation during carcinogenesis has been widely discussed in recent years. However, the pan-cancer DNA methylation biomarkers and corresponding biological mechanisms were seldom investigated. We identified differentially methylated sites and regions from 5,056 The Cancer Genome Atlas (TCGA) samples across 10 cancer types and then validated the findings using 48 manually annotated datasets consisting of 3,394 samples across nine cancer types from Gene Expression Omnibus (GEO). All samples’ DNA methylation profile was evaluated with Illumina 450K microarray to narrow down the batch effect. Nine regions were identified as commonly differentially methylated regions across cancers in TCGA and GEO cohorts. Among these regions, a DNA fragment consisting of ∼1,400 bp detected inside the HOXA locus instead of the boundary may relate to the co-expression attenuation of genes inside the locus during carcinogenesis. We further analyzed the 3D DNA interaction profile by the publicly accessible Hi-C database. Consistently, the HOXA locus in normal cell lines compromised isolated topological domains while merging to the domain nearby in cancer cell lines. In conclusion, the dysregulation of the HOXA locus provides a novel insight into pan-cancer carcinogenesis.

scholarly journals Evaluation of the prognostic value of CBXs in gastric cancer patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mengya He ◽  
Limin Yue ◽  
Haiyan Wang ◽  
Feiyan Yu ◽  
Mingyang Yu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Target Genes ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Genetic Alterations ◽  
Genetic Mutation ◽  
The Cancer Genome Atlas ◽  
Normal Tissues ◽  
Interactive Analysis ◽  
Gastric Cancer Patients

AbstractChromobox (CBX) proteins were suggested to exert epigenetic regulatory and transcriptionally repressing effects on target genes and might play key roles in the carcinogenesis of a variety of carcinomas. Nevertheless, the functions and prognostic significance of CBXs in gastric cancer (GC) remain unclear. The current study investigated the roles of CBXs in the prognosis of GC using the Oncomine, The Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, The Cancer Genome Atlas (TCGA), and cBioPortal databases. CBX1/2/3/4/5 were significantly upregulated in GC tissues compared with normal tissues, and CBX7 was downregulated. Multivariate analysis showed that high mRNA expression levels of CBX3/8 were independent prognostic factors for prolonged OS in GC patients. In addition, the genetic mutation rate of CBXs was 37% in GC patients, and genetic alterations in CBXs showed no association with OS or disease-free survival (DFS) in GC patients. These results indicated that CBX3/8 can be prognostic biomarkers for the survival of GC patients.

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