TRIM58 is a prognostic biomarker remodeling tumor microenvironment in KRAS-driven lung adenocarcinoma

2021 ◽  
Author(s):  
Xiaowei Chen ◽  
Yu Wang ◽  
Xiao Qu ◽  
Fenglong Bie ◽  
Yadong Wang ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Lung Adenocarcinoma ◽  
Prognostic Biomarker ◽  
Expression Profiles ◽  
The Cancer Genome Atlas ◽  
Follicular Helper ◽  
Follicular Helper T Cell ◽  
Cancer Genome Atlas ◽  
Genome Atlas ◽  
Potential Biomarkers

Aim: To comprehensively analyze the expression profiles of ubiquitin-related genes (URGs) and determine potential biomarkers in KRAS-driven lung adenocarcinoma (LUAD). Materials & methods: Differential expression analyses were performed between KRAS-wild and KRAS-mutant LUAD samples from The Cancer Genome Atlas database, and 34 URGs were screened out. ESTIMATE and CIBERSORT methods were used to calculate the ratio of immune and stromal components. Results & conclusion: TRIM58 was positively correlated with abundances of M2 macrophages and resting mast cells and negatively correlated with follicular helper T-cell abundances in KRAS-driven LUAD. TRIM58 was a potential prognosis-associated indicator for tumor microenvironment modulation and played a key role in TME-specific AS landscapes alterations in KRAS-driven LUAD.

scholarly journals ITGB1-DT/ARNTL2 axis may be a novel biomarker in lung adenocarcinoma: a bioinformatics analysis and experimental validation

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Bai-Quan Qiu ◽  
Xia-Hui Lin ◽  
Song-Qing Lai ◽  
Feng Lu ◽  
Kun Lin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Cox Regression ◽  
Malignant Tumors ◽  
Expression Profiles ◽  
The Cancer Genome Atlas ◽  
Hub Genes ◽  
Immune Infiltration ◽  
Prognostic Effect ◽  
Cancer Genome Atlas

Abstract Background Lung cancer is one of the most lethal malignant tumors that endangers human health. Lung adenocarcinoma (LUAD) has increased dramatically in recent decades, accounting for nearly 40% of all lung cancer cases. Increasing evidence points to the importance of the competitive endogenous RNA (ceRNA) intrinsic mechanism in various human cancers. However, behavioral characteristics of the ceRNA network in lung adenocarcinoma need further study. Methods Groups based on SLC2A1 expression were used in this study to identify associated ceRNA networks and potential prognostic markers in lung adenocarcinoma. The Cancer Genome Atlas (TCGA) database was used to obtain the patients' lncRNA, miRNA, and mRNA expression profiles, as well as clinical data. Informatics techniques were used to investigate the effect of hub genes on prognosis. The Cox regression analyses were performed to evaluate the prognostic effect of hub genes. The methylation, GSEA, and immune infiltration analyses were utilized to explore the potential mechanisms of the hub gene. The CCK-8, transwell, and colony formation assays were performed to detect the proliferation and invasion of lung cancer cells. Results We eventually identified the ITGB1-DT/ARNTL2 axis as an independent fact may promote lung adenocarcinoma progression. Furthermore, methylation analysis revealed that hypo-methylation may cause the dysregulated ITGB1-DT/ARNTL2 axis, and immune infiltration analysis revealed that the ITGB1-DT/ARNTL2 axis may affect the immune microenvironment and the progression of lung adenocarcinoma. The CCK-8, transwell, and colonu formation assays suggested that ITGB1-DT/ARNTL2 promotes the progression of lung adenocarcinoma. And hsa-miR-30b-3p reversed the ITGB1/ARNTL2-mediated oncogenic processes. Conclusion Our study identified the ITGB1-DT/ARNTL2 axis as a novel prognostic biomarker affects the prognosis of lung adenocarcinoma.

scholarly journals Screening and Identifying m6A Regulators as an Independent Prognostic Biomarker in Pancreatic Cancer Based on The Cancer Genome Atlas Database

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Bi Lin ◽  
Yangyang Pan ◽  
Dinglai Yu ◽  
Shengjie Dai ◽  
Hongwei Sun ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cox Regression ◽  
Malignant Tumors ◽  
Expression Profiles ◽  
Tumor Therapy ◽  
Disease Free Survival ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Background. Pancreatic cancer is one of the most malignant tumors of the digestive system, and its treatment has rarely progressed for the last two decades. Studies on m6A regulators for the past few years have seemingly provided a novel approach for malignant tumor therapy. m6A-related factors may be potential biomarkers and therapeutic targets. This research is focused on the gene characteristics and clinical values of m6A regulators in predicting prognosis in pancreatic cancer. Methods. In our study, we obtained gene expression profiles with copy number variation (CNV) data and clinical characteristic data of 186 patients with pancreatic cancer from The Cancer Genome Atlas (TCGA) portal. Then, we determined the alteration of m6a regulators and their correlation with clinicopathological features using the log-rank tests, Cox regression model, and chi-square test. Additionally, we validated the prognostic value of m6A regulators in the International Cancer Genome Consortium (ICGC). Results. The results suggested that pancreatic cancer patients with ALKBH5 CNV were associated with worse overall survival and disease-free survival than those with diploid genes. Additionally, upregulation of the writer gene ALKBH5 had a positive correlation with the activation of AKT pathways in the TCGA database. Conclusion. Our study not only demonstrated genetic characteristic changes of m6A-related genes in pancreatic cancer and found a strong relationship between the changes of ALKBH5 and poor prognosis but also provided a novel therapeutic target for pancreatic cancer therapy.

scholarly journals METTL3-Mediated m6A mRNA Modification of FBXW7 Suppresses Lung Adenocarcinoma

2020 ◽  
Author(s):  
Yingtong Wu ◽  
Ning Chang ◽  
Yong Zhang ◽  
Xinxin Zhang ◽  
Leidi Xu ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Cell Model ◽  
Biological Effects ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Luciferase Reporter ◽  
Rna Immunoprecipitation ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Abstract BackgroundFBXW7 m6A modification plays an important role in lung adenocarcinoma (LUAD) progression; however, the underlying mechanisms remain unclear.MethodsThe correlation between FBXW7 and various genes related to m6A modification was analyzed using The Cancer Genome Atlas database. The regulatory effects of METTL3 on FBXW7 mRNA m6A modification were examined in a cell model, and the underlying mechanism was determined by methylated RNA immunoprecipitation, RNA immunoprecipitation, luciferase reporter, and mutagenesis assays. In vitro experiments were performed to further explore the biological effects of METTL3-mediated FBXW7 m6A modification on LUAD development.ResultsDecreased FBXW7 expression was accompanied by downregulated METTL3 expression in human LUAD tissues and was associated with a worse prognosis for LUAD in The Cancer Genome Atlas database. m6A was highly enriched in METTL3-mediated FBXW7 transcripts, and increased m6A modification in the coding sequence region increased its translation. Functionally, METTL3 overexpression or knockdown affected the apoptosis and proliferation phenotype of LUAD cells by regulating FBXW7 m6A modification and expression. Furthermore, FBXW7 overexpression in METTL3-depleted cells partially restored the suppression of LUAD cells in vitro and in vivo.ConclusionsOur findings reveal that METTL3 positively regulates FBXW7 expression and confirm the tumor-suppressive role of m6A-modified FBXW7, thus providing insight into its epigenetic regulatory mechanisms in LUAD initiation and development.

scholarly journals Aging-Related Tumor Microenvironment Changes Could Worsen The Prognosis of GBM Patients

2020 ◽  
Author(s):  
Hongwang Song ◽  
Xiaojun Fu ◽  
Chenxing Wu ◽  
Shouwei Li
Keyword(s):  
Tumor Microenvironment ◽  
Epithelial Mesenchymal Transition ◽  
Close Correlation ◽  
Underlying Mechanism ◽  
The Cancer Genome Atlas ◽  
Future Research ◽  
Mesenchymal Transition ◽  
Cancer Genome Atlas ◽  
Differential Expressed Genes ◽  
Genome Atlas

Abstract Background: Glioblastoma multiforme (GBM) is the most malignant tumor in human brain, with highly heterogeneity among different patients. Age could function as an incidence and prognosis risk factor for many tumors.Method: A series of bioinformatic experiments were conducted to evaluate the differences of incidence, differential expressed genes, enriched pathways with the data from Surveillance, Epidemiology, and End Results (SEER) program, the cancer genome atlas (TCGA) and Chinese glioma genome atlas (CGGA) project.Results: We discovered in our present study that distinct difference of incidence and prognosis of different aged GBM patients. By a series of bioinformatic method, we found that the tumor associated fibroblasts (TAFs) was the most crucial tumor microenvironment (TME) component that led to this phenomenon. Epithelial-mesenchymal transition (EMT) could be the mechanism by which TAFs regulate the progression of GBM. Conclusion: We have proposed a close correlation between age and GBM incidence and prognosis, and propose the underlying mechanism behind this correlation by mining different databases, which laid the foundation for future research.

scholarly journals The Cancer Genome Atlas expression profiles of low-grade gliomas

2014 ◽  
Vol 36 (4) ◽  
pp. E23 ◽  
Author(s):  
David D. Gonda ◽  
Vincent J. Cheung ◽  
Karra A. Muller ◽  
Amit Goyal ◽  
Bob S. Carter ◽  
...  
Keyword(s):  
Cpg Island ◽  
Expression Profiles ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Molecular Characteristics ◽  
Low Grade ◽  
Cpg Island Methylator Phenotype ◽  
Low Grade Gliomas ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Differentiating between low-grade gliomas (LGGs) of astrocytic and oligodendroglial origin remains a major challenge in neurooncology. Here the authors analyzed The Cancer Genome Atlas (TCGA) profiles of LGGs with the goal of identifying distinct molecular characteristics that would afford accurate and reliable discrimination of astrocytic and oligodendroglial tumors. They found that 1) oligodendrogliomas are more likely to exhibit the glioma-CpG island methylator phenotype (G-CIMP), relative to low-grade astrocytomas; 2) relative to oligodendrogliomas, low-grade astrocytomas exhibit a higher expression of genes related to mitosis, replication, and inflammation; and 3) low-grade astrocytic tumors harbor microRNA profiles similar to those previously described for glioblastoma tumors. Orthogonal intersection of these molecular characteristics with existing molecular markers, such as IDH1 mutation, TP53 mutation, and 1p19q status, should facilitate accurate and reliable pathological diagnosis of LGGs.

scholarly journals Molecular Profiling of Core Immune-Escape Genes Highlights LCK Has Potential to Reshape TME in Melanoma

2021 ◽  
Author(s):  
Duoli Zhang ◽  
Zhuo Zhang ◽  
Shixin Xiang ◽  
Mintao Xiao ◽  
Yao Zhang ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Immune System ◽  
Tumor Microenvironment ◽  
Immune Escape ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Cox Regression Analysis ◽  
Tumor Environment ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Abstract Background: The game between the immune system of the organism and the tumor is a dynamic course of events. Once the escape phase is reached, the tumor will overcome the limitations of the immune system and the tumor will progress. Objective: This study aimed to determine the potential tumor environment-based prognostic biomarkers related to immunotherapy in melanoma. Methods: 471 tumor samples and 398 normal samples were extracted from The Cancer Genome Atlas and The Genotype-Tissue Expression. Furthermore, a core set of immune-escape genes were collected from previous studies and a set of immune-related genes were obtained from IMMPORT database. Through overlapping these two sets of genes, a set of core immune-escape related genes were identified. In the next place, we conducted a systematic analysis of core immune-escape related genes through The Cancer Genome Atlas cohort and identified independent prognostic factors in melanoma. Through CIBERSORT, ssGSEA algorithm and TIMER database, we explored the potential of independent prognostic factors to reshape the tumor microenvironment.Results: Through Kaplan-Meier as well as univariate cox regression analysis of expression profiles and clinical information obtained from the TCGA cohort, we found that high LCK expression was associated with prolonged overall survival. In addition, the expression level of LCK was significantly correlated with the dysregulation of the infiltration level of immune cells in the tumor microenvironment. Conclusions: In this study, we determined LCK as a biomarker that is significantly associated with tumor environment and has significant prognostic significance. Meanwhile, immunotherapeutic approaches targeting LCK in tumor cells may provide a new perspective for the treatment of melanoma.

scholarly journals Expression profiles and prognostic significance of WNT family members in glioma via bioinformatic analysis

2020 ◽  
Vol 40 (3) ◽  
Author(s):  
Anqi Xu ◽  
Huiping Yang ◽  
Kunjie Gao ◽  
Zhengming Zhan ◽  
Zibin Song ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Expression Profiles ◽  
Prognostic Significance ◽  
Bioinformatic Analysis ◽  
The Cancer Genome Atlas ◽  
Poor Overall Survival ◽  
Cancer Genome Atlas ◽  
Expression Status ◽  
Genome Atlas

Abstract Aims: The dysregulation and essential role of WNTs in glioma have been widely implicated. However, there is a paucity of literature on the expression status of all the 19 WNTs in glioma. Our study was aimed to evaluate the expression and prognostic values of the 19 WNTs in glioma. Methods: mRNA expression and clinical data were retrieved from the Cancer Genome Atlas (TCGA) database, Chinese Glioma Genome Atlas (CGGA), GTEx and ONCOMINE databases. The 50 frequent neighbor genes of WNT5A and WNT10B were shown with PPI network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Results: We found that the mRNA expression of WNT5A was significantly higher in glioma; however, the WNT10B expression was significantly lower in glioma. Furthermore, the expression of WNT5A and WNT10B was associated with the clinicopathology of glioma. The survival analysis revealed that the higher expressions of WNT5A and WNT16 were associated poor overall survival (OS) in patients with glioma. Conversely, overexpression of WNT3, WNT5B, and WNT10B was associated with better OS. Finally, Go and KEGG analysis revealed WNT5A was associated with multiple signal translations, and crucial oncogenes (EGFR and MDM2) and 2 important tumor suppressors (PTEN and IKN4a/ARF) were found closely correlated with WNT5A in glioma. Conclusion: Among 19WNTs, WNT5A can serve as a candidate to diagnose and therapy glioma, while WNT10B might be valuable for anti-glioma research. The presumed direction was provided to explore the relation of WNTs signal and multiple pathways in glioma.

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