scholarly journals Overexpression of HPRT1 is associated with poor prognosis in head and neck squamous cell carcinoma

2020 ◽  
Author(s):  
Mohsen Ahmadi ◽  
Pegah Mousavi ◽  
Negin Saffarzadeh ◽  
Fatemeh Hajiesmaeili ◽  
Leila Habibipour
Keyword(s):  
Cell Cycle ◽  
Head And Neck ◽  
Squamous Cell ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Hypoxanthine Phosphoribosyl Transferase ◽  
Pcr Analysis ◽  
Clinical Value

AbstractHypoxanthine phosphoribosyl transferase (HPRT1), as a salvage pathway enzyme, plays a crucial role in modulating the cell cycle and has been reported to be overexpressed in multiple cancers. Nevertheless, the relationship between the HPRT1 and Head and Neck Squamous Cell Carcinomas (HNSCC) has not been investigated so far. We first evaluated the expression of HPRT1 at transcriptomic and proteomic levels in tumor and healthy control tissues and its clinical value using The Cancer Genome Atlas (TCGA), Human Protein Atlas, Kaplan-Meier Plotter databases, GSE107591, and quantitative real-time PCR analysis. Then, we employed the COSMIC and cBioPortal databases to assess the mutations of the HPRT1 gene and their association with survival outcomes of patients with HNSCC. Finally, we performed the functional enrichment analysis for HPRT1 co-expressed genes in HNSCC utilizing the Enrichr database. The mRNA and protein expressions of HPRT1 were significantly elevated in HNSCC compared with normal tissues. Besides, the upregulation of HPRT1 expression was correlated with age, sex, pathological stage, and histological grades of HNSCC patients. Moreover, the increased expression of HPRT1 in cancer tissues exhibited a strong capacity for being a promising biomarker for the diagnosis and prognosis of patients with HNSCC. The co-expressed genes of HPRT1 were mainly enriched in several cancer-related processes such as DNA replication and cell cycle. The present study demonstrated that the overexpression of HPRT1 is significantly correlated with the progression of HNSCC and may serve as a useful biomarker for the early detection and risk stratification of patients with HNSCC.

scholarly journals CCTs as new biomarkers for the prognosis of head and neck squamous cancer

Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 672-688
Author(s):  
Yanbo Dong ◽  
Siyu Lu ◽  
Zhenxiao Wang ◽  
Liangfa Liu
Keyword(s):  
Head And Neck ◽  
Survival Data ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Advanced Tumor Stage ◽  
Expression Levels ◽  
T Complex ◽  
Advanced Tumor ◽  
Squamous Cancer

AbstractThe chaperonin-containing T-complex protein 1 (CCT) subunits participate in diverse diseases. However, little is known about their expression and prognostic values in human head and neck squamous cancer (HNSC). This article aims to evaluate the effects of CCT subunits regarding their prognostic values for HNSC. We mined the transcriptional and survival data of CCTs in HNSC patients from online databases. A protein–protein interaction network was constructed and a functional enrichment analysis of target genes was performed. We observed that the mRNA expression levels of CCT1/2/3/4/5/6/7/8 were higher in HNSC tissues than in normal tissues. Survival analysis revealed that the high mRNA transcriptional levels of CCT3/4/5/6/7/8 were associated with a low overall survival. The expression levels of CCT4/7 were correlated with advanced tumor stage. And the overexpression of CCT4 was associated with higher N stage of patients. Validation of CCTs’ differential expression and prognostic values was achieved by the Human Protein Atlas and GEO datasets. Mechanistic exploration of CCT subunits by the functional enrichment analysis suggests that these genes may influence the HNSC prognosis by regulating PI3K-Akt and other pathways. This study implies that CCT3/4/6/7/8 are promising biomarkers for the prognosis of HNSC.

scholarly journals Identification of a prognostic long non-coding RNA signature in breast cancer

2020 ◽  
Author(s):  
Gaochen Lan ◽  
Xiaoling Yu ◽  
Yanna Zhao ◽  
Jinjian Lan ◽  
Wan Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cox Regression ◽  
Prognostic Biomarker ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Cox Regression Analysis

Abstract Background: Breast cancer is the most common malignant disease among women. At present, more and more attention has been paid to long non-coding RNAs (lncRNAs) in the field of breast cancer research. We aimed to investigate the expression profiles of lncRNAs and construct a prognostic lncRNA for predicting the overall survival (OS) of breast cancer.Methods: The expression profiles of lncRNAs and clinical data with breast cancer were obtained from The Cancer Genome Atlas (TCGA). Differentially expressed lncRNAs were screened out by R package (limma). The survival probability was estimated by the Kaplan‑Meier Test. The Cox Regression Model was performed for univariate and multivariate analysis. The risk score (RS) was established on the basis of the lncRNAs’ expression level (exp) multiplied regression coefficient (β) from the multivariate cox regression analysis with the following formula: RS=exp a1 * β a1 + exp a2 * β a2 +……+ exp an * β an. Functional enrichment analysis was performed by Metascape.Results: A total of 3404 differentially expressed lncRNAs were identified. Among them, CYTOR, MIR4458HG and MAPT-AS1 were significantly associated with the survival of breast cancer. Finally, The RS could predict OS of breast cancer (RS=exp CYTOR * β CYTOR + exp MIR4458HG * β MIR4458HG + exp MAPT-AS1 * β MAPT-AS1). Moreover, it was confirmed that the three-lncRNA signature could be an independent prognostic biomarker for breast cancer (HR=3.040, P=0.000).Conclusions: This study established a three-lncRNA signature, which might be a novel prognostic biomarker for breast cancer.

scholarly journals Transcriptomic Analysis Revealed an Emerging Role of Alternative Splicing in Embryonal Tumor with Multilayered Rosettes

Genes ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 1108
Author(s):  
Dina Hesham ◽  
Shahenda El-Naggar
Keyword(s):  
Cell Cycle ◽  
Alternative Splicing ◽  
Wnt Signaling Pathway ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Embryonal Tumor ◽  
Alternative Splicing Events ◽  
Regulation Of Cell Cycle

Embryonal tumor with multilayered rosettes (ETMR) is an aggressive and rare pediatric embryonal brain tumor. Amplification of C19MC microRNA cluster and expression of LIN28 are distinctive features of ETMR. Despite the increasing efforts to decipher ETMR, the biology remains poorly understood. To date, the role of aberrant alternative splicing in ETMR has not been thoroughly investigated. In the current study, a comprehensive analysis was performed on published unprocessed RNA-seq reads of tissue-matched ETMR and fetal controls datasets. Gene expression was quantified in samples using Kallisto/sleuth pipeline. For the alternative splicing analysis, STAR, SplAdder and rMATS were used. Functional enrichment analysis was subsequently performed using Metascape. The expression analysis identified a total of 3622 differentially expressed genes (DEGs) between ETMR and fetal controls while 1627 genes showed differential alternative splicing patterns. Interestingly, genes with significant alternative splicing events in ETMR were identified to be involved in signaling pathways such as ErbB, mTOR and MAPK pathways as well as ubiquitin-mediated proteolysis, cell cycle and autophagy. Moreover, up-regulated DEGs with alternative splicing events were involved in important biological processes including nuclear transport, regulation of cell cycle and regulation of Wnt signaling pathway. These findings highlight the role of aberrant alternative splicing in shaping the ETMR tumor landscape, and the identified pathways constitute potential therapeutic targets.

Functional Enrichment Analysis by David in Transgenic MYCN Zebrafish Model

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5114-5114
Author(s):  
Li-Jing Shen ◽  
Fang-Yuan Chen ◽  
Lan-Fang Cao ◽  
Yong Zhang ◽  
Hua Zhong
Keyword(s):  
Cell Cycle ◽  
Signaling Pathways ◽  
Microarray Analysis ◽  
Conflicts Of Interest ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Mapk Signaling ◽  
Functional Enrichment ◽  
Tgfβ Signaling ◽  
Apoptosis Pathway

Abstract Abstract 5114 Introduction The MYCN oncogene encodes a basic helix-loop-helix/leucine zipper (bHLH/LZ) transcription factor that is frequently overexpressed in hematologic malignancies neoplasms (including acute leukemia, T-cell lymphoma, and so on). MYCN acts as a poor prognostic marker to promote an aggressive phenotype. However, the mechanisms of action and pathways affected by MYCN are still largely unclear. Methods We induced murine MYCN gene overexpression in embryonic zebrafish through heat-shock promoter and established stable germline Tg(MYCN:HSE:EGFP) zebrafish. RNA was extracted at 3 days post fertilization from wild type (WT) and transgenic zebrafish F1 generation (TG) embryo hematopoietic cells, collected by the flow cytometer, for microarray analysis. The samples were processed and subsequently analyzed in triplicate on Zebrafish Oligo Microarrays (Agilent Technologies), containing 43, 554 sets of probe, at the Advanced Throughput Inc. The microarrays were scanned in an Agilent DNA Microarray Scanner and the images were processed using Feature Extraction software. A False Discovery Rate≤0. 05 for overall interactions effect and P<0. 001 between comparisons were used to determine differentially expressed genes (DEG). Ingenuity Pathway Analysis and DAVID performed the functional analysis of DEG. Results Microarray analysis revealed 626 (342 genes up-regulated and 284 genes down-regulated) DEG that showed >2-fold change in TG comparing with that of WT. Using functional enrichment analysis by DAVID, several signaling pathways were regulated in TG samples (Table 1). MAPK signaling pathway was high activated through FGF, PDGF, BDNF and CACN high expression, promoting up-regulated of Ras and MKP, enhancing phosphorylation and leading to increase of cells proliferation. TGFβ signaling was inhibited by up-regulation of IFN Ã and Smad 6/7, which negative control of TGFβR and Smad 2/3. Further, we found that MYCN enhances the expression of skp2, via decreased p21 and increased CDK2, promoting cell cycle progression (Fig. 1). In addition, overexpression of MYCN weakened the function of mismatch repair, base excision repair, while increased apoptosis pathway mediated by p53 (up-regulated Bid gene). Meanwhile, Glycolysis/gluconeogenesis pathway was significantly up-regulated in TG fish. Conclusions Overexpression of MYCN induced up-regulation of cell proliferation and Glycolysis/gluconeogenesis pathway (as the Warburg effect in rapidly proliferating tumors), attenuation of repair function, all of which are phenomena associated with proliferation and malignancies transformation of blood cell feature. We found that MYCN down-regulates p27kip1, p57kip2 and p21cip1 through up-regulate Skp2, thus up-regulates CDK2, CycA, CycB, CycD and CycE. All above changes shortened the time taken to progress through the cell cycle. Increased MARK signaling and decreased TGFβ signaling pathways also contributed to promote cell cycle. (Red star marks the up-regulated genes). Disclosures: No relevant conflicts of interest to declare.

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 Long Noncoding RNA RP11-357H14.17 Plays an Oncogene Role in Gastric Cancer by Activating ATF2 Signaling and Enhancing Treg Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Tang Xiaoli ◽  
Wang Wenting ◽  
Zhang Meixiang ◽  
Zuo Chunlei ◽  
Hu Chengxia
Keyword(s):  
Gastric Cancer ◽  
Noncoding Rna ◽  
Prognostic Value ◽  
Malignant Tumors ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Treg Cells ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Biological Behavior

Background. Gastric cancer (GC) is one of the most common malignant tumors in the world. The potential functions and mechanisms of long noncoding RNAs (lncRNAs) in GC development are still unclear. It is of great significance to explore the prognostic value of LncRNA signatures for GC. Methods. LncRNAs differently expressed in GC and their prognostic value were studied based on The Cancer Genome Atlas (TCGA) database. The functional regulatory network and immune infiltration of RP11-357H14.17 were further studied using a variety of bioinformatics tools and databases. Results. We found that the high expression of RP11-357H14.17 was closely associated with shortened overall survival (OS) and poor prognosis in gastric cancer patients. We also found that its expression was related to clinical features including tumor volume, metastasis, and differentiation. Functional enrichment analysis revealed that RP11-357H14.17 is closely related to enhanced DNA replication and metabolism; ssGSEA analysis implied the oncogenic roles of RP11-357H14.17 was related to ATF2 signaling and Treg cell differentiation. Furthermore, we verified such link by using real-time PCR and IHC staining in human GC samples. Conclusion. We demonstrate that RP11-357H14.17 may play a crucial role in the occurrence, development, and malignant biological behavior of gastric cancer as a potential prognostic marker for gastric cancer.

scholarly journals Identification of long noncoding RNA RP11-89K21.1 and RP11-357H14.17 as prognostic signature of endometrial carcinoma via integrated bioinformatics analysis

2020 ◽  
Author(s):  
Lingling Gao ◽  
Xin Nie ◽  
Wenchao Zhang ◽  
Rui Gou ◽  
Yuexin Hu ◽  
...  
Keyword(s):  
Endometrial Carcinoma ◽  
Noncoding Rna ◽  
Growth Regulation ◽  
Malignant Tumors ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Biological Behavior ◽  
Vessel Development

Abstract Background: Endometrial carcinoma (EC) is one of the most common malignant tumors in gynecology. The potential functions and mechanisms of long noncoding RNAs (lncRNAs) in the occurrence and progression of EC remains unclear. It’s meaningful to explore lncRNAs signature for providing prognostic value of EC. Methods：The differentially expressed lncRNAs and their prognostic values in EC were investigated based on The Cancer Genome Atlas (TCGA) database; the transcriptional factors (TFs), the competing endogenous RNA (ceRNA) mechanism, functional regulatory network and immune infiltration of RP11-89K21.1 and RP11-357H14.17 were further explored by various bioinformatics tools and databases. Results: We first identified high expression of RP11-89K21.1 and RP11-357H14.17 were closely associated with shorten overall survival (OS) and poor prognosis in patients with EC. We also elucidated the networks of transcription factor and co-expression genes associated with RP11-89K21.1 and RP11-357H14.17. Furthermore, the ceRNA network mechanism was successfully constructed through 2 lncRNAs (RP11-89K21.1 and RP11-357H14.17), 11 miRNAs and 183 mRNAs. Functional enrichment analysis revealed that the targeting genes of RP11-89K21.1 and RP11-357H14.17 were strongly associated with microRNAs in cancer, vessel development, growth regulation, growth factor and cell differentiation, and involved in pathways including pathways in cancer, microRNAs in cancer and apoptotic signaling pathway. Conclusions: We demonstrated for the first time that RP11-89K21.1 and RP11-357H14.17 may play crucial roles in the occurrence, development and malignant biological behavior of EC, and can be regarded as potential prognostic biomarkers for EC.

scholarly journals Six-long Non-coding RNA Signature to Predict the Prognosis of Lung Adenocarcinoma

2020 ◽  
Author(s):  
Yang Wang ◽  
Chengping Hu
Keyword(s):  
Lung Adenocarcinoma ◽  
Cox Regression ◽  
Survival Rates ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Protein Coding ◽  
Cox Regression Analysis ◽  
Protein Coding Genes

Abstract Background: Long non-coding RNAs (lncRNAs) have been reported to play essential roles in tumorigenesis and cancers prognosis, and they can be a potential cancer prognostic markers. However, in lung adenocarcinoma(LUAD), how lncRNA signatures predict the survival of patients is poorly understood. Our study aims to explore lncRNA signatures and prognostic function in LUAD.Methods: The expression and prognosis data of lncRNAs in LUAD patients was collected from the Cancer Genome Atlas (TCGA) data. All analyses were performed using the R package (version 3.6.2). Metascape, STRING and Cytoscape were used for enrichment analysis and function prediction of the lncRNA co-expressed protein-coding genes.Results: We have collected lncRNA expression data in 466 LUAD tumors, and a six-lncRNA signature(RP11-79H23.3, RP11-309M7.1, CTD-2357A8.3, RP11-108P20.4, U47924.29, LHFPL3-AS2) has been shown to be significantly related to LUAD patients’ overall survival. According to the lncRNA signatures, the high-risk and low-risk groups were divided in LUAD patients with different survival rates. Further multivariable cox regression analysis showed that the prognostic value of this signature was independent of clinical factors. The potential functional roles and hub co-expressed protein-coding genes in the six prognostic lncRNAs are shown in the functional enrichment analysis.Conclusions: These results showed that these six lncRNAs could be independent predicted prognostic biomarkers in LUAD patients.

scholarly journals A novel ferroptosis-related gene signature associated with cell cycle for prognosis prediction in patients with clear cell renal cell carcinoma

BMC Cancer ◽  
2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Siteng Chen ◽  
Encheng Zhang ◽  
Tuanjie Guo ◽  
Jialiang Shao ◽  
Tao Wang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Renal Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Related Gene ◽  
Cell Renal Cell Carcinoma ◽  
Prognosis Model

Abstract Background It is of great urgency to explore useful prognostic markers for patients with clear cell renal cell carcinoma (ccRCC). Prognostic models based on ferroptosis-related gene (FRG) in ccRCC is poorly reported for now. Methods Comprehensive analysis of 22 FRGs were performed in 629 ccRCC samples from two independent patient cohorts. We carried out least absolute shrinkage and selection operator analysis to screen out prognosis-related FRGs and constructed prognosis model for patients with ccRCC. Weighted gene co-expression network analysis was also carried out for potential functional enrichment analysis. Results Based on the TCGA cohort, a total of 11 prognosis-associated FRGs were selected for the construction of the prognosis model. Significantly differential overall survival (hazard ratio = 3.61, 95% CI: 2.68–4.87, p < 0.0001) was observed between patients with high and low FRG score in the TCGA cohort, which was further verified in the CPTAC cohort with hazard ratio value of 5.13 (95% CI: 1.65–15.90, p = 0.019). Subgroup survival analysis revealed that our FRG score could significantly distinguish patients with high survival risk among different tumor stages and different tumor grades. Functional enrichment analysis illustrated that the process of cell cycle, including cell cycle-mitotic pathway, cytokinesis pathway and nuclear division pathway, might be involved in the regulation of ccRCC through ferroptosis. Conclusions We developed and verified a FRG signature for the prognosis prediction of patients with ccRCC, which could act as a risk factor and help to update the tumor staging system when integrated with clinicopathological characteristics. Cell cycle-related pathways might be involved in the regulation of ccRCC through ferroptosis.

scholarly journals Identification of Key Genes Affecting the Tumor Microenvironment and Prognosis of Triple-Negative Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Jiarong Yi ◽  
Wenjing Zhong ◽  
Haoming Wu ◽  
Jikun Feng ◽  
Xiazi Zouxu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Ppi Network ◽  
Key Genes

Although the tumor microenvironment (TME) plays an important role in the development of many cancers, its roles in breast cancer, especially triple-negative breast cancer (TNBC), are not well studied. This study aimed to identify genes related to the TME and prognosis of TNBC. Firstly, we identified differentially expressed genes (DEG) in the TME of TNBC, using Expression data (ESTIMATE) datasets obtained from the Cancer Genome Atlas (TCGA) and Estimation of Stromal and Immune cells in Malignant Tumor tissues. Next, survival analysis was performed to analyze the relationship between TME and prognosis of TNBC, as well as determine DEGs. Genes showing significant differences were scored as alternative genes. A protein-protein interaction (PPI) network was constructed and functional enrichment analysis conducted using the DEG. Proteins with a degree greater than 5 and 10 in the PPI network correspond with hub genes and key genes, respectively. Finally, CCR2 and CCR5 were identified as key genes in TME and prognosis of TNBC. Finally, these results were verified using Gene Expression Omnibus (GEO) datasets and immunohistochemistry of TNBC patients. In conclusion, CCR2 and CCR5 are key genes in the TME and prognosis of TNBC with the potential of prognostic biomarkers in TNBC.

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