scholarly journals The Immunological Role of CDK4/6 and Potential Mechanism Exploration in Ovarian Cancer

2022 ◽  
Vol 12 ◽  
Author(s):  
Chen Liu ◽  
Yuhan Huang ◽  
Yaoyuan Cui ◽  
Jun Zhou ◽  
Xu Qin ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Poor Prognosis ◽  
Animal Experiments ◽  
Tissue Expression ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Public Data ◽  
Sting Pathway ◽  
And Function ◽  
Antigen Presenting

BackgroundOvarian cancer (OC) is one of the most lethal gynecologic cancers. Growing evidence has proven that CDK4/6 plays a key role in tumor immunity and the prognosis of many cancers. However, the expression and function of CDK4/6 in OC remain unclear. Therefore, we aimed to explore the influence of CDK4/6 in OC, especially on immunity.MethodsWe analyzed CDK4/6 expression and prognosis using The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and Genotype Tissue Expression (GTEx) data. Subsequently, we used the cytoHubba plug-in of Cytoscape software and starBase to identify the noncoding RNAs (ncRNAs) regulating CDK4/6. Finally, we verified the effect of CDK4/6 on immunity in OC cell lines and animal models.ResultsCDK4/6 expression was higher in OC tissues than in normal ovarian tissues, and the high expression levels of CDK4/6 contributed to the immunosuppressive state of OC and were thus related to the poor prognosis of OC patients. This was also in general agreement with the results of OC cell line and animal experiments. Mechanistically, the CDK4/6 inhibitor palbociclib increased the secretion of interferon (IFN)-γ and the interferon-stimulated gene (ISG) response, thereby upregulating the expression of antigen-presenting molecules; this effect was partly dependent on the STING pathway and thus activated immunity in OC. Additionally, according to public data, the LRRC75A-AS1-hsa-miR-330-5p axis could inhibit the immune response of OC patients by upregulating CDK4/6, leading to a poor prognosis.ConclusionCDK4/6 affects the immune microenvironment of OC and correlates with the prognosis of OC patients.

scholarly journals Prognostic Value of Genes Related with Tumor Microenvironment in Ovarian Cancer

2020 ◽  
Author(s):  
Shimei Li ◽  
Jiyi Yao ◽  
Shen Zhang ◽  
Xinchuan Zhou ◽  
Xinbao Zhao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ovarian Cancer ◽  
Tumor Microenvironment ◽  
Poor Prognosis ◽  
External Validation ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Gene Expression Signatures ◽  
Poor Outcomes ◽  
Geo Database

Abstract Background Ovarian cancer (OV) is the fifth leading cause of cancer death among females. Growing evidence supports a key role of tumor microenvironment in growth, progress, and metastasis of OV. However, the impacts of gene expression signatures related with OV microenvironment on prognosis have not been well-established . This study aimed to apply ESTIMATE algorithm to extract genes related with tumor microenvironment that predicted poor outcomes in OV patients. Methods The gene expression profile of OV samples were downloaded from The Cancer Genome Atlas (TCGA) database. The immune scores and stromal scores of 469 OV samples were available based on the ESTIMATE algorithm. To better understand impacts of gene expression signatures related with OV microenvironment on prognosis, these samples were categorized based on their ESTIMATE scores into high and low score groups. A different OV cohort from the Gene Expression Omnibus (GEO) database was used for external validation. Results The molecular subtypes in OV patients were correlated with stromal scores, in which the mesenchymal subtype had the highest stromal scores (p < 0.0001). Poor prognosis were found in patients (especially for patients with overall survivals (OS) < 5 years) with higher stromal score (p = 0.0376). 449 differentially expressed genes (DEGs) in stromal scores group were identified and 26 DEGs were significantly associated with poor prognosis in OV patients (p < 0.05). Eventually, 6 genes have further validated to be significantly associated with poor outcomes in 40 patients from a different OV cohort of GEO database (p < 0.05). Conclusion In this study, several genes related with tumor microenvironment that predicted poor prognosis in OV patients were extracted. In addition, some previously overlooked genes could be potential prognostic biomarkers for OV.

scholarly journals Novel Epigenetic Eight-Gene Signature Predictive of Poor Prognosis and MSI-Like Phenotype in Human Metastatic Colorectal Carcinomas

Cancers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 158
Author(s):  
Valentina Condelli ◽  
Giovanni Calice ◽  
Alessandra Cassano ◽  
Michele Basso ◽  
Maria Grazia Rodriquenz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Poor Prognosis ◽  
Cpg Island ◽  
Colon Adenocarcinoma ◽  
Gene Signature ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Cpg Island Methylator Phenotype ◽  
Prognostic Information ◽  
Global Methylation

Epigenetics is involved in tumor progression and drug resistance in human colorectal carcinoma (CRC). This study addressed the hypothesis that the DNA methylation profiling may predict the clinical behavior of metastatic CRCs (mCRCs). The global methylation profile of two human mCRC subgroups with significantly different outcome was analyzed and compared with gene expression and methylation data from The Cancer Genome Atlas COlon ADenocarcinoma (TCGA COAD) and the NCBI GENE expression Omnibus repository (GEO) GSE48684 mCRCs datasets to identify a prognostic signature of functionally methylated genes. A novel epigenetic signature of eight hypermethylated genes was characterized that was able to identify mCRCs with poor prognosis, which had a CpG-island methylator phenotype (CIMP)-high and microsatellite instability (MSI)-like phenotype. Interestingly, methylation events were enriched in genes located on the q-arm of chromosomes 13 and 20, two chromosomal regions with gain/loss alterations associated with adenoma-to-carcinoma progression. Finally, the expression of the eight-genes signature and MSI-enriching genes was confirmed in oxaliplatin- and irinotecan-resistant CRC cell lines. These data reveal that the hypermethylation of specific genes may provide prognostic information that is able to identify a subgroup of mCRCs with poor prognosis.

scholarly journals Development and Validation of a Prognostic Nomogram Based on DNA Methylation-Driven Genes for Patients With Ovarian Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Min Zhou ◽  
Shasha Hong ◽  
Bingshu Li ◽  
Cheng Liu ◽  
Ming Hu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dna Methylation ◽  
Mrna Expression ◽  
Risk Score ◽  
Cox Regression ◽  
Expression Profiles ◽  
Figo Stage ◽  
Prognostic Indicator ◽  
Tissue Expression ◽  
The Cancer Genome Atlas

Background: DNA methylation affects the development, progression, and prognosis of various cancers. This study aimed to identify DNA methylated-differentially expressed genes (DEGs) and develop a methylation-driven gene model to evaluate the prognosis of ovarian cancer (OC).Methods: DNA methylation and mRNA expression profiles of OC patients were downloaded from The Cancer Genome Atlas, Genotype-Tissue Expression, and Gene Expression Omnibus databases. We used the R package MethylMix to identify DNA methylation-regulated DEGs and built a prognostic signature using LASSO Cox regression. A quantitative nomogram was then drawn based on the risk score and clinicopathological features.Results: We identified 56 methylation-related DEGs and constructed a prognostic risk signature with four genes according to the LASSO Cox regression algorithm. A higher risk score not only predicted poor prognosis, but also was an independent poor prognostic indicator, which was validated by receiver operating characteristic (ROC) curves and the validation cohort. A nomogram consisting of the risk score, age, FIGO stage, and tumor status was generated to predict 3- and 5-year overall survival (OS) in the training cohort. The joint survival analysis of DNA methylation and mRNA expression demonstrated that the two genes may serve as independent prognostic biomarkers for OS in OC.Conclusion: The established qualitative risk score model was found to be robust for evaluating individualized prognosis of OC and in guiding therapy.

Synthesize Analysis of the IFN-γ and Immune Infiltrates of m6A RNA Methylation Regulators in Human Skin Cutaneous Melanoma

2021 ◽  
Author(s):  
Yuqi Wang ◽  
Le Huang ◽  
Mingxin Li ◽  
Yunfeng Qi
Keyword(s):  
Cutaneous Melanoma ◽  
Cox Regression ◽  
Tissue Expression ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Mortality And Morbidity ◽  
Tumour Immunity ◽  
Ifn Γ ◽  
Expression Pathways ◽  
Immune Pathway

Abstract Background: SKCM is a major common cancer with highly mortality and morbidity, causing about 72% of deaths in skin carcinoma. In recent years, more scholars have selected one or two m6A regulatory factors to explore the abnormal expression and potential mechanism of m6A in tumorigenesis and development. So as to find the relevant biomarkers in the whole tumorigenesis process.Methods: In current study, we used public transcriptome datasets from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and Genotype-Tissue Expression (GTEx) to investigate the relationships between N6-methyl adenosine(m6A) regulators genes and Skin cutaneous melanoma (SKCM). Then, SKCM patients were grouped based on the cluster analysis of m6A regulators expression. Compared the relationship between Interferon (IFN)-γ and immune infiltrates. Results: Based on the survival curves of subgroups, we selected 20 potential predictive m6A-related genes were overexpressed in SKCM. And based on the typing results, we got the 15 differential expression genes between the three groups. Four of them (CYP2U1, SEMA6A, GRIA2, and TSPAN13) were selected in Cox regression, which were significant expression in overall survival(p<0.05). Interferon (IFN)-γ is a central cytokine, which effecting immune-provoking and recognizing transformed cells in anti-tumour immunity. Conclusions: To investigate the correlation between IFN-γ and SKCM. We have identified that IFN-γ is a potential factor for cancer therapy, and affecting expression pathways of SKCM. Among them, IFN-γ and WTAP were the most positive correlation. These sights suggest that IFN-γ can potentially be utilized for immune pathway such as melanoma skin cancer.

scholarly journals OSmfs: An Online Interactive Tool to Evaluate Prognostic Markers for Myxofibrosarcoma

Genes ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1523
Author(s):  
Huimin Li ◽  
Longxiang Xie ◽  
Qiang Wang ◽  
Yifang Dang ◽  
Xiaoxiao Sun ◽  
...  
Keyword(s):  
Gene Expression ◽  
Poor Prognosis ◽  
Analysis Data ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Prognostic Biomarkers ◽  
Rank Test ◽  
Web Tool ◽  
Kaplan Meier ◽  
Cox Analysis

Myxofibrosarcoma is a complex genetic disease with poor prognosis. However, more effective biomarkers that forebode poor prognosis in Myxofibrosarcoma remain to be determined. Herein, utilizing gene expression profiling data and clinical follow-up data of Myxofibrosarcoma cases in three independent cohorts with a total of 128 Myxofibrosarcoma samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, we constructed an easy-to-use web tool, named Online consensus Survival analysis for Myxofibrosarcoma (OSmfs) to analyze the prognostic value of certain genes. Through retrieving the database, users generate a Kaplan–Meier plot with log-rank test and hazard ratio (HR) to assess prognostic-related genes or discover novel Myxofibrosarcoma prognostic biomarkers. The effectiveness and availability of OSmfs were validated using genes in ever reports predicting the prognosis of Myxofibrosarcoma patients. Furthermore, utilizing the cox analysis data and transcriptome data establishing OSmfs, seven genes were selected and considered as more potentially prognostic biomarkers through overlapping and ROC analysis. In conclusion, OSmfs is a promising web tool to evaluate the prognostic potency and reliability of genes in Myxofibrosarcoma, which may significantly contribute to the enrichment of novelly potential prognostic biomarkers and therapeutic targets for Myxofibrosarcoma.

scholarly journals Regulatory T Cells in Human Ovarian Cancer

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Dong-Jun Peng ◽  
Rebecca Liu ◽  
Weiping Zou
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Immune Suppression ◽  
Immune Cells ◽  
Clinical Settings ◽  
Human Ovarian Cancer ◽  
Cancer Microenvironment ◽  
Cellular Mechanisms ◽  
And Function ◽  
Antigen Presenting

Multiple layers of suppressive components including regulatory T (TReg) cells, suppressive antigen-presenting cells, and inhibitory cytokines form suppressive networks in the ovarian cancer microenvironment. It has been demonstrated that as a major suppressive element, TRegcells infiltrate tumor, interact with several types of immune cells, and mediate immune suppression through different molecular and cellular mechanisms. In this paper, we focus on human ovarian cancer and will discuss the nature of TRegcells including their subsets, trafficking, expansion, and function. We will briefly review the development of manipulation of TRegcells in preclinical and clinical settings.

Elucidating the pathogenesis of esophageal adenocarcinoma through meta-analysis of public data.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 71-71
Author(s):  
Kamal Khorfan ◽  
Jihad Aljabban ◽  
Saad Syed ◽  
Hussam Salhi ◽  
Aderinola Adejare ◽  
...  
Keyword(s):  
Gene Expression ◽  
Esophageal Adenocarcinoma ◽  
Poor Prognosis ◽  
Meta Analysis ◽  
Statistical Significance ◽  
Suppressor Gene ◽  
Gene Expression Omnibus ◽  
Incidence And Mortality ◽  
Public Data ◽  
Log Ratio

71 Background: Esophageal adenocarcinoma (EAC) is the sixth most common cause of cancer-related deaths worldwide. It commonly arises in the setting of reflux disease and Barett’s esophagus. It remains incurable and holds a poor prognosis. Dissecting the genetic signature of EAC can pave new therapeutic avenues. Methods: We employed our Search Tag Analyze Resource (STARGEO) platform to conduct meta-analysis using the National Center for Biotechnology’s (NCBI) Gene Expression Omnibus (GEO). We tagged 151 tumor samples from EAC patients and 62 normal esophageal samples as a control. We then analyzed the signature in Ingenuity Pathway Analysis, restricting genes that showed statistical significance (p < 0.05) and an absolute experimental log ratio greater than 0.15 between tumor and control. Results: Our analysis revealed granulocyte adhesion and diapedesis and FXR/RXR signaling as top canonical pathways. TGFB1, TNF, and beta-estradiol were top upstream regulators with predicted activation. TGFB1 and TNF expression have been correlated with poor prognosis in EAC. Also, beta-estradiol has tumorigenic activity in several cancers but has not been investigated in EAC. Among the top upregulated genes were oncogenic genes such as tetraspanin 8, the antiapoptotic factor OLFM4, and the protease cathepsin E (CTSE). SPINK1, a trypsin inhibitor with recently suggested role in cancer, and the choline transporter SLC44A4, a drug target for pancreatic cancer, were also upregulated. The most downregulated genes included alcohol dehydrogenase 7, associated with EAC in alcohol-drinkers, and the pro-apoptotic gene CRCT1. We also found downregulation of the serine peptidase inhibitor SPINK7. SPINK7 is involved in maintaining epithelial-barrier integrity and is implicated in eosinophilic esophagitis pathogenesis. Lastly, there was downregulation of the candidate tumor suppressor gene transglutaminase 3. Conclusions: Despite screening efforts, EAC incidence and mortality continues to increase as does the need for better treatment. This meta-analysis defines the significant gene expression changes within causal disease processes to provide markers for detection, prognostic insight, and therapeutic value for EAC.

Bioinformatics Combined with Quantitative Proteomics Analyses and Identification of Potential Biomarkers in Cholangiocarcinoma

2020 ◽  
Author(s):  
Zijian Da ◽  
Long Gao ◽  
Gang Su ◽  
Jia Yao ◽  
Wenkang Fu ◽  
...  
Keyword(s):  
Risk Factor ◽  
Poor Prognosis ◽  
Independent Risk Factor ◽  
Primary Tumour ◽  
Absolute Quantification ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Integrated Analysis ◽  
Protein Levels

Abstract Background Cholangiocarcinoma(CCA)is an invasive malignancy arising from biliary epithelial cells; it is the most common primary tumour of the bile tract and has a poor prognosis. The aim of this study was to screen prognostic biomarkers for CCA by integrated multiomics analysis. Methods The GSE32225 dataset was derived from the Gene Expression Omnibus (GEO) database and comprehensively analysed by using R software and The Cancer Genome Atlas (TCGA) database to obtain the differentially expressed RNAs (DERNAs) associated with CCA prognosis. Quantitative isobaric tags for relative and absolute quantification (iTRAQ) proteomics was used to screen differentially expressed proteins (DEPs) between CCA and nontumour tissues. Through integrated analysis of DERNA and DEP data, we obtained candidate proteins APOF, ITGAV and CASK, and immunohistochemistry was used to detect the expression of these proteins in CCA. The relationship between CASK expression and CCA prognosis was further analysed. Results Through bioinformatics analysis, 875 DERNAs were identified, of which 10 were associated with the prognosis of the CCA patients. A total of 487 DEPs were obtained by using the iTRAQ technique. Comprehensive analysis of multiomics data showed that CASK, ITGAV and APOF expression at both the mRNA and protein levels were different in CCA compared with nontumour tissues. CASK was found to be expressed in the cytoplasm and nucleus of CCA cells in 38 (45%) of 84 patients with CCA. Our results suggested that patients with positive CASK expression had significantly better overall survival (OS) and recurrence-free survival (RFS) than those with negative CASK expression. Univariate and multivariate analyses demonstrated that negative expression of CASK was a significantly independent risk factor for OS and RFS in CCA patients. Conclusions CASK may be a tumour suppressor; its low expression is an independent risk factor for a poor prognosis in CCA patients, and so it could be used as a clinically valuable prognostic marker.

Prognostic Values and Prospective Pathway Signaling of miR-30a in Ovarian Cancer: A Study Based on Gene Expression Omnibus and Bioinformatics Analysis

2020 ◽  
Author(s):  
Weijia Lu ◽  
Yunyu Wu ◽  
CanXiong Lu ◽  
Ting Zhu ◽  
ZhongLu Ren ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ovarian Cancer ◽  
Target Genes ◽  
Ovarian Tissue ◽  
Differentially Expressed Gene ◽  
Enrichment Analysis ◽  
Gene Expression Omnibus ◽  
Hub Genes ◽  
Protein Protein Interaction ◽  
Public Data

Abstract Objective MicroRNAs (MiRNAs) is considered to play an important role in the occurrence and development of ovarian cancer(OC). Although miRNAs has been widely recognized in ovarian cancer, the role of hsa-miR-30a-5p (miR-30a) in OC has not been fully elucidated. Methods Through the analysis of public data sets in Gene Expression Omnibus (GEO) database and literature review, the significance of miR-30a expression in OC is evaluated. Three mRNA datasets of OC and normal ovarian tissue, GSE14407, GSE18520 and GSE36668, were downloaded from GEO to find the differentially expressed gene (DEG). Then the target genes of hsa-miR-30a-5p were predicted by miRWALK3.0 and TargetScan. Then, the gene overlap between DEG and the predicted target genes of miR-30a in OC was analyzed by Gene Ontology (GO) enrichment analysis. Protein-protein interaction (PPI) network was constructed by STRING and Cytoscape, and the effect of HUB gene on the prognosis of OC was analyzed. Results A common pattern of up-regulation of miR-30a in OC was found. A total of 225 DEG, were identified, both OC-related and miR-30a-related. Many DEG are enriched in the interactions of intracellular matrix tissue, ion binding and biological process regulation. Among the 10 major Hub genes analyzed by PPI, five Hub genes were significantly related to the overall poor survival of OC patients, in which the low expression of ESR1 ,MAPK10, Tp53 and the high expression of YKT ,NSF were related to poor prognosis of OC.

scholarly journals microRNA-1271-5p/TIAM1 suppresses the progression of ovarian cancer through inactivating Notch signaling pathway

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Feng-Juan Han ◽  
Jia Li ◽  
Ying Shen ◽  
Ying Guo ◽  
Yi-Chao Liu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Target Gene ◽  
Notch Signaling Pathway ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Western Blot Assay

Abstract Objective Ovarian cancer (OC) has been regarded as the most malignant gynecological neoplasm and often confers grave outcomes owing to the frequent metastasis and high recurrence. A previous study has demonstrated that miR-1271-5p is implicated in OC progression, however, the possible mechanism of it remains unknown. The purpose of this investigation was to explore how miR-1271-5p regulates the progression of OC. Methods Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were employed to analyze the differentially expressed miRNAs or genes as well as their corresponding prognostic values. miR-1271-5p expression in OC cells was examined by qRT-PCR. Cell counting kit 8 (CCK-8), colony formation, and transwell tests were conducted to evaluate the proliferation, migration and invasion potentials. Bioinformatics prediction and luciferase activity analysis were utilized to predict and verify the target gene of miR-1271-5p. Western blot assay was carried out to measure protein expression. Results miR-1271-5p was significantly decreased in OC and its down-regulation was associated with the grave outcome of OC patients. Upregulation of miR-1271-5p inhibited cell viability, but miR-1271-5p knockdown promoted the proliferation of OC cells. TIAM1 was a direct target gene of miR-1271-5p and expressed in OC tissues at higher level. High expression of TIAM1 induced the poorer prognosis of patients with OC. Further functional analyses showed that the suppressive role of miR-1271-5p on OC cell malignant behaviors was overturned by the upregulation of TIAM1. The protein levels of Cyclin D1, HES1, NOTCH and NUMB were remarkably changed due to the abnormal expression of miR-1271-5p and TIAM1. Conclusion To sum up, miR-1271-5p inhibits proliferation, invasion and migration of OC cells by directly repressing TIAM1 to inactivate the Notch signaling pathway, which provides an alternative therapeutic candidate for the advancement of OC treatment.

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