scholarly journals Identification of significant genes as prognostic markers and potential tumor suppressors in lung adenocarcinoma via bioinformatical analysis

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Mingze Lu ◽  
Xiaowen Fan ◽  
Weilin Liao ◽  
Yijiao Li ◽  
Lijie Ma ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Ontology ◽  
Tumor Suppressor ◽  
Lung Adenocarcinoma ◽  
Tumor Suppressor Genes ◽  
Prognostic Markers ◽  
Ppi Network ◽  
Normal Tissues ◽  
Potential Tumor Suppressor ◽  
Six Genes

Abstract Background Lung adenocarcinoma (LAC) is the predominant histologic subtype of lung cancer and has a complicated pathogenesis with high mortality. The purpose of this study was to identify differentially expressed genes (DEGs) with prognostic value and determine their underlying mechanisms. Methods Gene expression data of GSE27262 and GSE118370 were acquired from the Gene Expression Omnibus database, enrolling 31 LAC and 31 normal tissues. Common DEGs between LAC and normal tissues were identified using the GEO2R tool and Venn diagram software. Next, the Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used to analyze the Gene Ontology and Kyoto Encyclopedia of Gene and Genome (KEGG) pathways. Then, protein-protein interaction (PPI) network of DEGs was visualized by Cytoscape with Search Tool for the Retrieval of Interacting Genes and central genes were identified via Molecular Complex Detection. Furthermore, the expression and prognostic information of central genes were validated via Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan-Meier analysis, respectively. Finally, DAVID, real-time PCR and immunohistochemistry were applied to re-analyze the identified genes, which were also further validated in two additional datasets from ArrayExpress database. Results First, 189 common DEGs were identified among the two datasets, including 162 downregulated and 27 upregulated genes. Next, Gene Ontology and KEGG pathway analysis of the DEGs were conducted through DAVID. Then, PPI network of DEGs was constructed and 17 downregulated central genes were identified. Furthermore, the 17 downregulated central genes were validated via GEPIA and datasets from ArrayExpress, and 12 of them showed a significantly better prognosis. Finally, six genes were identified significantly enriched in neuroactive ligand-receptor interactions (EDNRB, RXFP1, P2RY1, CALCRL) and Rap1 signaling pathway (TEK, P2RY1, ANGPT1) via DAVID, which were further validated to be weakly expressed in LAC tissues via RNA quantification and immunohistochemistry analysis. Conclusions The low expression pattern and relation to prognosis indicated that the six genes were potential tumor suppressor genes in LAC. In conclusion, we identified six significantly downregulated DEGs as prognostic markers and potential tumor suppressor genes in LAC based on integrated bioinformatics methods, which could act as potential molecular markers and therapeutic targets for LAC patients.

scholarly journals Computational Identification of Tumor Suppressor Genes Based on Gene Expression Profiles in Normal and Cancerous Gastrointestinal Tissues

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Qingrong Sun ◽  
Md. Nazim Uddin ◽  
Mengyuan Li ◽  
Xiaosheng Wang ◽  
Maode Lai
Keyword(s):  
Gene Expression ◽  
Small Intestine ◽  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Suppressor Genes ◽  
Expression Levels ◽  
Suppressive Function ◽  
Normal Tissues ◽  
Gi Cancers ◽  
Tumor Suppressive Function

Cancer prevails in various gastrointestinal (GI) organs, such as esophagus, stomach, and colon. However, the small intestine has an extremely low cancer risk. It is interesting to investigate the molecular cues that could explain the significant difference in cancer incidence rates among different GI tissues. Using several large-scale normal and cancer tissue genomics datasets, we compared the gene expression profiling between small intestine and other GI tissues and between GI cancers and normal tissues. We identified 17 tumor suppressor genes (TSGs) which showed significantly higher expression levels in small intestine than in other GI tissues and significantly lower expression levels in GI cancers than in normal tissues. These TSGs were mainly involved in metabolism, immune, and cell growth signaling-associated pathways. Many TSGs had a positive expression correlation with survival prognosis in various cancers, confirming their tumor suppressive function. We demonstrated that the downregulation of many TSGs was associated with their hypermethylation in cancer. Moreover, we showed that the expression of many TSGs inversely correlated with tumor purity and positively correlated with antitumor immune response in various cancers, suggesting that these TSGs may exert their tumor suppressive function by promoting antitumor immunity. Furthermore, we identified a transcriptional regulatory network of the TSGs and their master transcriptional regulators (MTRs). Many of MTRs have been recognized as tumor suppressors, such as HNF4A, ZBTB7A, p53, and RUNX3. The TSGs could provide new molecular cues associated with tumorigenesis and tumor development and have potential clinical implications for cancer diagnosis, prognosis, and treatment.

scholarly journals Bioinformatics study on genes related to a high-risk postoperative recurrence of lung adenocarcinoma

2021 ◽  
Vol 104 (3) ◽  
pp. 003685042110180
Author(s):  
Xiao Lin ◽  
Meng Zhou ◽  
Zehong Xu ◽  
Yusheng Chen ◽  
Fan Lin
Keyword(s):  
Cell Cycle ◽  
Gene Ontology ◽  
High Risk ◽  
Lung Adenocarcinoma ◽  
Candidate Genes ◽  
Postoperative Recurrence ◽  
High Expression ◽  
Ppi Network ◽  
Hub Genes ◽  
Expression Levels

In this study, we aimed to screen out genes associated with a high risk of postoperative recurrence of lung adenocarcinoma and investigate the possible mechanisms of the involvement of these genes in the recurrence of lung adenocarcinoma. We identify Hub genes and verify the expression levels and prognostic roles of these genes. Datasets of GSE40791, GSE31210, and GSE30219 were obtained from the Gene Expression Omnibus database. Enrichment analysis of gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed for the screened candidate genes using the DAVID database. Then, we performed protein–protein interaction (PPI) network analysis through the database STRING. Hub genes were screened out using Cytoscape software, and their expression levels were determined by the GEPIA database. Finally, we assessed the relationships of Hub genes expression levels and the time of survival. Forty-five candidate genes related to a high-risk of lung adenocarcinoma recurrence were screened out. Gene ontology analysis showed that these genes were enriched in the mitotic spindle assembly checkpoint, mitotic sister chromosome segregation, G2/M-phase transition of the mitotic cell cycle, and ATP binding, etc. KEGG analysis showed that these genes were involved predominantly in the cell cycle, p53 signaling pathway, and oocyte meiosis. We screened out the top ten Hub genes related to high expression of lung adenocarcinoma from the PPI network. The high expression levels of eight genes (TOP2A, HMMR, MELK, MAD2L1, BUB1B, BUB1, RRM2, and CCNA2) were related to short recurrence-free survival and they can be used as biomarkers for high risk of lung adenocarcinoma recurrence. This study screened out eight genes associated with a high risk of lung adenocarcinoma recurrence, which might provide novel insights into researching the recurrence mechanisms of lung adenocarcinoma as well as into the selection of targets in the treatment of the disease.

Genetic basis of ruminant headgear and rapid antler regeneration

Science ◽  
2019 ◽  
Vol 364 (6446) ◽  
pp. eaav6335 ◽  
Author(s):  
Yu Wang ◽  
Chenzhou Zhang ◽  
Nini Wang ◽  
Zhipeng Li ◽  
Rasmus Heller ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Genetic Basis ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Neural Crest Stem Cells ◽  
Organ Regeneration ◽  
Similar Gene

Ruminants are the only extant mammalian group possessing bony (osseous) headgear. We obtained 221 transcriptomes from bovids and cervids and sequenced three genomes representing the only two pecoran lineages that convergently lack headgear. Comparative analyses reveal that bovid horns and cervid antlers share similar gene expression profiles and a common cellular basis developed from neural crest stem cells. The rapid regenerative properties of antler tissue involve exploitation of oncogenetic pathways, and at the same time some tumor suppressor genes are under strong selection in deer. These results provide insights into the evolutionary origin of ruminant headgear as well as mammalian organ regeneration and oncogenesis.

E6-Associated Protein (E6-AP): A Potential Tumor Suppressor Protein for Non-Hodgkin Lymphoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4336-4336
Author(s):  
Shazia Zafar ◽  
Sathish Srinivasan ◽  
Zafar Nawaz
Keyword(s):  
T Cell ◽  
Tumor Suppressor ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Lymphoid Tissue ◽  
Tumor Suppressor Genes ◽  
Tumor Suppressor Protein ◽  
Non Hodgkin Lymphoma ◽  
T Cell Lymphomas ◽  
Potential Tumor Suppressor

Abstract Over the past decade considerable progress has been made in cloning and characterization of potential tumor suppressor genes. Tumor suppressors have a repressive effect on the regulation of the cell cycle or promote apoptosis and sometimes do both. The function of tumor suppressor proteins fall into several categories, tumor suppressor genes are presumed to encode negative regulator of proliferation and inhibit mitotic activity. Loss of tumor suppressor protein or function of a tumor suppressor protein has been shown to be associated with the cancer formation. Continued investigation into the biochemical and cell biological functions of the tumor suppressor is critical to elucidate the mechanisms by which they normally inhibit proliferation/tumor development and to provide a molecular explanation for their frequent inactivation in cancer. Our laboratory has previously shown that the expression of E6-associated protein (E6-AP), which is an E3 ubiquitin-protein ligase and a coactivator of nuclear hormone receptors, is significantly reduced in human cancers having epithelial cell origin such as breast cancer. In this prospective study, we want to extend our observation to the cancers originating from lymphoid tissue. Non-Hodgkin lymphoma is a cancer of lymphoid tissue. The main cell type found in lymphoid tissue is the lymphocyte. The 2 main types of lymphocytes are B-lymphocytes (B-cells) and T-lymphocytes (T-cells). B-cell lymphomas are much more common than T-cell lymphomas. In the U. S., 85% of all cases of non-Hodgkin lymphoma come from B lymphocytes (B-cell) and 15% from T lymphocytes (T-cell). We performed immunohistochemistry analysis to investigate the expression pattern of E6-AP in normal lymph nodes and lymphoid tumors. Tissue micro arrays representing samples from 60 different patients were analyzed in this study. Our analysis suggest that on an average there was about 55 % reduction in E6-AP protein levels in B-cell lymphomas (P =0.0001) and 98.5 % reduction in E6-AP levels in T-cell lymphomas (P =0.0002) compared to normal lymph node. Based on our previous studies in breast and prostate tumors and considering our current finding of reduced/loss of E6-AP in lymphoid tumors, we propose that E6-AP may act as a potential tumor suppressor protein. This proposed idea is consistent with our in vivo data generated from E6-AP null mice which shows that the number of B- and T-cells are significantly increased in spleen compared to normal wild-type animals. Taken together our data establish the role of E6-AP as a potential growth and tumor suppressor protein.

The ING tumor suppressor genes and their specific role in the pathogenesis of renal cell carcinoma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10045-10045
Author(s):  
E. Nichiporuk ◽  
T. Lebedeva ◽  
M. Gasser ◽  
F. Hillig ◽  
J. Lutz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Renal Cell Carcinoma ◽  
Tumor Suppressor ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Tumor Suppressor Genes ◽  
Stage I ◽  
Suppressor Genes ◽  
Tumor Stages ◽  
Ifn Γ

10045 Background: The inhibitor of growth (ING) family of tumor suppressor genes is involved in cell cycle arrest, regulation of gene transcription as well as DNA repair. p33ING1b plays an important role in the pathogenesis of certain carcinomas by modulation of p53. We analyzed p33ING1b and p29ING4 gene expression together with specific immune responses in patients with renal cell carcinoma (n=50) at different tumor stages. Methods: Peripheral blood lymphocytes (PBMCs) from patients (Robson stage I-IV) were stimulated with pools of synthetic overlapping peptides of the p33ING1b or p29ING4 sequences encompassing the full length sequence of these two genes. PBMCs and tumor specimens were further characterized (ELISPOT, FACS, immunohistology, Real Time PCR). Results: T cells from stage I/II patients expressed higher IL-10 (n=5) than IFN-γ (n=5) levels in response to p29ING4 peptides. However, distinct residues of peptides were found that induced a Th2 type response (IL 10, n=5) in stage III/IV patients. Interestingly, distinct residues induced a Th1 (IFN-γ, n=5) response in the latter patients. Lymphocytes stimulated with p33ING1b peptide pools expressed IFN-γ as well as IL-10, independently from the tumor stage. Remarkably, immunohistochemical staining as well as Real Time PCR analysis of tumor specimens revealed higher numbers of CD4/CD8, CD4/CD25, CD4/Foxp3, CD4/CTLA-4, and NK cells as well as IL-10, IFN-γ, and Annexin V expression at the tumor site of stage I/II patients than later tumor stages. However, stronger staining and gene expression of p33ING1b as well as p29ING4 together with a reduced staining and expression of p53 was observed in stage III/IV patients. A correlation between the stage and the grading of the tumor was not present. Conclusions: In order to exert its function as a growth arrest and apoptosis inducing protein, p53 needs to interact with other tumor suppressor genes like the ING gene family. Subsequently, the loss of ING function may be a potential mechanism for the inactivation of p53 function in renal cell carcinoma. The results of this study may provide the basis for immune therapeutical strategies (induction of apoptosis or of a Th1 response using a vaccination protocol in particular with p29ING4 in the early stage of the disease) in renal cell carcinoma. No significant financial relationships to disclose.

Detection and Analysis of RNAs Expression Profile for Methylated Candidate Tumor Suppressor Genes in Nasopharyngeal Carcinoma

2019 ◽  
Vol 19 (6) ◽  
pp. 772-782
Author(s):  
Shuang Zhao ◽  
Ye Zhang ◽  
Xujun Liang ◽  
Maoyu Li ◽  
Fang Peng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Nasopharyngeal Carcinoma ◽  
Tumor Suppressor ◽  
Promoter Methylation ◽  
Tumor Suppressor Genes ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Suppressor Genes ◽  
Multiple Tumor

Background:DNA methylation, which acts as an expression regulator for multiple Tumor Suppressor Genes (TSGs), is believed to play an important role in Nasopharyngeal Carcinoma (NPC) development.Methods:We compared the effects of 5-aza-2-deoxycytidine (decitabine, DAC) on gene expression using RNA sequencing in NPC cells.Results:We analyzed Differentially Expressed Genes (DEGs) in NPC cells using DAC demethylation treatment and found that 2182 genes were significantly upregulated (≥ 2-fold change), suggesting that they may play a key role in cell growth, proliferation, development, and death. For data analysis, we used the Gene Ontology database and pathway enrichment analysis of the DEGs to discover differential patterns of DNA methylation associated with changes in gene expression. Furthermore, we evaluated 74 methylated candidate TSGs from the DEGs in NPC cells and summarized these genes in several important signaling pathways frequently disrupted by promoter methylation in NPC tumorigenesis.Conclusion:Our study analyzes the DEGs and identifies a set of genes whose promoter methylation in NPC cells is reversed by DAC. These genes are potential substrates of DNMT inhibitors and may serve as tumor suppressors in NPC cells.

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