scholarly journals FXYD5 is a Marker for Poor Prognosis and a Potential Driver for Metastasis in Ovarian Carcinomas

2015 ◽  
Vol 14 ◽  
pp. CIN.S30565 ◽  
Author(s):  
Pichai Raman ◽  
Timothy Purwin ◽  
Richard Pestell ◽  
Aydin Tozeren

Ovarian cancer (OC) is a leading cause of cancer mortality, but aside from a few well-studied mutations, very little is known about its underlying causes. As such, we performed survival analysis on ovarian copy number amplifications and gene expression datasets presented by The Cancer Genome Atlas in order to identify potential drivers and markers of aggressive OC. Additionally, two independent datasets from the Gene Expression Omnibus web platform were used to validate the identified markers. Based on our analysis, we identified FXYD5, a glycoprotein known to reduce cell adhesion, as a potential driver of metastasis and a significant predictor of mortality in OC. As a marker of poor outcome, the protein has effective antibodies against it for use in tissue arrays. FXYD5 bridges together a wide variety of cancers, including ovarian, breast cancer stage II, thyroid, colorectal, pancreatic, and head and neck cancers for metastasis studies.

2021 ◽  
Vol 65 (2) ◽  
Author(s):  
Lulu Le ◽  
Ji Luo ◽  
Haifang Wu ◽  
Ling Chen ◽  
Xiaoli Tang ◽  
...  

Endometrial cancer (EC) is the most common gynecologic malignancy and still remains clinically challenging. We aimed to explore the potential biomarkers of EC and provide a theoretical basis for early screening and targeted therapy. The available transcriptome data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were analyzed to identify differentially expressed genes. Immunohistochemistry was performed to detect gene expression. We analyzed the associations of MYBL2 with clinicopathological features and survival time and the biological effect of MYBL2 on the proliferation of EC cells. The effect of MYBL2 silencing on the transcriptome of EC cell model was analyzed by RNA-Seq. MYBL2 was significantly upregulated with obvious copy number alteration (CNA) in EC. Copy number amplification significantly increased MYBL2 mRNA expression, which led to a poor prognosis and severe pathological types of EC. Additionally, MYBL2 silencing significantly inhibited proliferation and induced apoptosis and G1-phase cell cycle arrest in EC cell lines. Our results indicate that MYBL2 is closely related to the cell cycle and apoptosis pathways in EC. The findings in this study provide evidence that MYBL2 can serve as a new candidate prognostic marker and a target for future therapeutic intervention in EC.


Cancers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 158
Author(s):  
Valentina Condelli ◽  
Giovanni Calice ◽  
Alessandra Cassano ◽  
Michele Basso ◽  
Maria Grazia Rodriquenz ◽  
...  

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.


2020 ◽  
Vol 40 (11) ◽  
Author(s):  
Wei Han ◽  
Biao Huang ◽  
Xiao-Yu Zhao ◽  
Guo-Liang Shen

Abstract Skin cutaneous melanoma (SKCM) is one of the most deadly malignancies. Although immunotherapies showed the potential to improve the prognosis for metastatic melanoma patients, only a small group of patients can benefit from it. Therefore, it is urgent to investigate the tumor microenvironment in melanoma as well as to identify efficient biomarkers in the diagnosis and treatments of SKCM patients. A comprehensive analysis was performed based on metastatic melanoma samples from the Cancer Genome Atlas (TCGA) database and ESTIMATE algorithm, including gene expression, immune and stromal scores, prognostic immune-related genes, infiltrating immune cells analysis and immune subtype identification. Then, the differentially expressed genes (DEGs) were obtained based on the immune and stromal scores, and a list of prognostic immune-related genes was identified. Functional analysis and the protein–protein interaction network revealed that these genes enriched in multiple immune-related biological processes. Furthermore, prognostic genes were verified in the Gene Expression Omnibus (GEO) databases and used to predict immune infiltrating cells component. Our study revealed seven immune subtypes with different risk values and identified T cells as the most abundant cells in the immune microenvironment and closely associated with prognostic outcomes. In conclusion, the present study thoroughly analyzed the tumor microenvironment and identified prognostic immune-related biomarkers for metastatic melanoma.


Genes ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1523
Author(s):  
Huimin Li ◽  
Longxiang Xie ◽  
Qiang Wang ◽  
Yifang Dang ◽  
Xiaoxiao Sun ◽  
...  

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.


2021 ◽  
Author(s):  
Jianting Du ◽  
Li-rong Xiao ◽  
Guobing Xu ◽  
Bin Zheng ◽  
Chun Chen

Abstract Background: Esophageal cancer (ESCA) is one of the most aggressive and lethal human malignant cancers. It is associated with poor overall survival (OS) and ranks sixth among the causes of cancer-related mortalities. MiR-1301-3p plays vital roles in a majority of malignancies. The aim of this study was to investigate the correlation between miR-1301-3p/NBL1 axis and prognosis of ESCA patients.Methods: We compared the miR-1301-3p expression levels between ESCA and normal esophageal tissues using MiRNAseq data retrieved from The Cancer Genome Atlas (TCGA) database. We employed UALCAN web platform, starBase v3.0 database, R software and GEPIA web platform to perform statistical analysis and data visualization. We then used TargetScan Human, miRDB and DIANA Tools databases to predict the miR-1301-3p target genes. Finally, we analyzed the expression patterns of the target genes as well as their prognostic value in ESCA.Results: There was an overexpression of miR-1301-3p in most malignancies, including ESCA (P<0.001). The miR-1301-3p expression levels were significantly related to age and histologic grade in primary ESCA (P<0.05), with high expression of miR-1301-3p being significantly associated with poor prognosis (Hazard ratio [HR]=1.88, P=0.012). NBL1 was identified as a potential target gene for miR-1301-3p and a negatively correlation in expression levels between the two genes was observed (r=-0.282, P<0.001). Notably, NBL1 was significantly downregulated in ESCA (P<0.001) and its low expression was significantly associated with poor prognosis of ESCA patients (HR=0.53, P=0.0063).Conclusion: miR-1301-3p is a potential biomarker for predicting prognosis of ESCA patients. It may regulate ESCA progression by regulating NBL1 expression.


2019 ◽  
Author(s):  
Quanhua Mu ◽  
Jiguang Wang

AbstractCopy number alteration (CNA), the abnormal number of copies of genomic regions, plays a key role in cancer initiation and progression. Current high-throughput CNA detection methods, including DNA arrays and genomic sequencing, are relatively expensive and require DNA samples at a microgram level, which are not achievable in certain occasions such as clinical biopsies or single-cell genomes. Here we proposed an alternative method—CNAPE to computationally infer CNA using gene expression data. A prior knowledge-aided machine learning model was proposed, trained and tested on the transcriptomic profiles with matched CNA data of 9,740 cancers from The Cancer Genome Atlas. Using brain tumors as a proof-of-concept study, CNAPE achieved over 90% accuracy in the prediction of arm-level CNAs. Prediction performance for 12 gene-level CNAs (commonly altered genes in glioma) was also evaluated, and CNAPE achieved reasonable accuracy. CNAPE is developed as an easy-to-use tool at http://wang-lab.ust.hk/software/Software.html.


2018 ◽  
Vol 33 (3) ◽  
pp. 293-300 ◽  
Author(s):  
Min-hang Zhou ◽  
Hong-wei Zhou ◽  
Mo Liu ◽  
Jun-zhong Sun

Purpose: The role of microRNA (miRNA) in cholangiocarcinoma was not clear. The aim of this study was to find the potential diagnostic and prognostic miRNA in cholangiocarcinoma patients. Methods: The miRNA expression profiles in cholangiocarcinoma patients from The Cancer Genome Atlas and Gene Expression Omnibus (GSE53870) were analyzed. The comparison of overall survival was performed using the Kaplan–Meier method. The targeted genes of prognostic miRNA were identified in miRanda, PicTar, or TargetScan, and their cell signaling pathways were analyzed by the Database for Annotation, Visualization and Integrated Discovery. Results: In The Cancer Genome Atlas and the Gene Expression Omnibus miRNA dataset, miR-92b and miR-99a were found with concordant directionality, up-regulated and down-regulated, respectively. In The Cancer Genome Atlas survival data, patients with the high level of miR-99b had obviously shorter overall survival time ( P=0.038). However, the level of miR-99a was not found to be significant. The 17 shared target genes of miR-92b were identified, such as DAB21IP, BCL21L11, SPHK2, PER2, and TSC1. The related pathways included positive regulation of transcription, positive regulation of cellular biosynthetic process, regulation of programmed cell death, etc. Conclusion: miR-92b was up-regulated in cholangiocarcinoma compared with normal controls. The high level of miR-92b was associated with adverse outcomes in cholangiocarcinoma patients, which might be partly explained by the targeted genes of miR-92b and their signaling pathways.


2021 ◽  
Vol 41 (1) ◽  
Author(s):  
Xianxue Zhang ◽  
Feng Yang ◽  
Zhenbao Wang

Abstract Immunotherapy is remarkably affected by the immune environment of the principal tumor. Nonetheless, the immune environment’s clinical relevance in stage IV gastric cancer (GC) is largely unknown. The gene expression profiles of 403 stage IV GC patients in the three cohorts: GEO (Gene Expression Omnibus, GSE84437 (n=292) and GSE62254 (n=77), and TCGA (The Cancer Genome Atlas, n=34) were used in the present study. Using four publicly available stage IV GC expression datasets, 29 immune signatures were expression profiled, and on this basis, we classified stage IV GC. The classification was conducted using the hierarchical clustering method. Three stage IV GC subtypes L, M, and H were identified representing low, medium, and high immunity, respectively. Immune correlation analysis of these three types revealed that Immune H exhibited a better prognostic outcome as well as a higher immune score compared with other subtypes. There was a noticeable difference in the three subgroups of HLA genes. Further, on comparing with other subtypes, CD86, CD80, CD274, CTLA4, PDCD1, and PDCD1LG2 had higher expression in the Immunity H subtype. In stage IV GC, potentially positive associations between immune and pathway activities were displayed, due to the enrichment of pathways including TNF signaling, Th-17 cell differentiation, and JAK-STAT signaling pathways in Immunity H vs Immunity L subtypes. External cohorts from TCGA cohort ratified these results. The identification of stage IV GC subtypes has potential clinical implications in stage IV GC treatment.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Gaojianyong Wang ◽  
Dimitris Anastassiou

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.


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