Expression of DUSP4 transcript variants as a potential biomarker for colorectal cancer

2020 ◽  
Vol 14 (8) ◽  
pp. 639-650
Author(s):  
Tatiana Varela ◽  
Vincent Laizé ◽  
Natércia Conceição ◽  
Paulo Caldeira ◽  
Ana Marreiros ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Kras Mutations ◽  
Normal Tissues ◽  
Potential Biomarker ◽  
Tumor Stages ◽  
Cancer Genome Atlas ◽  
Poorly Differentiated ◽  
Genome Atlas

Aim: To provide novel data on the expression of DUSP4 transcripts in colorectal cancer (CRC) tissues and to explore their potential as biomarkers. Materials & methods: DUSP4 transcripts expression was determined by quantitative real-time PCR in tissues from 28 CRC patients. Their association with clinicopathological factors and survival analysis was performed. Data from 380 CRC patients available at The Cancer Genome Atlas project were also analyzed. Results: All transcripts were overexpressed in CRC tissues. Variant X1 was the most upregulated and associated with KRAS mutations and poorly differentiated tumor. Overexpression of DUSP4 transcripts could distinguish all tumor stages from normal tissues. Similar results were found in The Cancer Genome Atlas cohort. Conclusion: DUSP4 transcripts have the potential to serve as diagnostic biomarkers for CRC, particularly variant X1.

scholarly journals Exceptional Chemotherapy Response in Metastatic Colorectal Cancer Associated With Hyper-Indel–Hypermutated Cancer Genome and Comutation of POLD1 and MLH1

2017 ◽  
pp. 1-12
Author(s):  
Manish R. Sharma ◽  
James T. Auman ◽  
Nirali M. Patel ◽  
Juneko E. Grilley-Olson ◽  
Xiaobei Zhao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Somatic Mutation ◽  
Mutation Rate ◽  
Germ Line ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Response To Chemotherapy ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Purpose A 73-year-old woman with metastatic colon cancer experienced a complete response to chemotherapy with dose-intensified irinotecan that has been durable for 5 years. We sequenced her tumor and germ line DNA and looked for similar patterns in publicly available genomic data from patients with colorectal cancer. Patients and Methods Tumor DNA was obtained from a biopsy before therapy, and germ line DNA was obtained from blood. Tumor and germline DNA were sequenced using a commercial panel with approximately 250 genes. Whole-genome amplification and exome sequencing were performed for POLE and POLD1. A POLD1 mutation was confirmed by Sanger sequencing. The somatic mutation and clinical annotation data files from the colon (n = 461) and rectal (n = 171) adenocarcinoma data sets were downloaded from The Cancer Genome Atlas data portal and analyzed for patterns of mutations and clinical outcomes in patients with POLE- and/or POLD1-mutated tumors. Results The pattern of alterations included APC biallelic inactivation and microsatellite instability high (MSI-H) phenotype, with somatic inactivation of MLH1 and hypermutation (estimated mutation rate > 200 per megabase). The extremely high mutation rate led us to investigate additional mechanisms for hypermutation, including loss of function of POLE. POLE was unaltered, but a related gene not typically associated with somatic mutation in colon cancer, POLD1, had a somatic mutation c.2171G>A [p.Gly724Glu]. Additionally, we noted that the high mutation rate was largely composed of dinucleotide deletions. A similar pattern of hypermutation (dinucleotide deletions, POLD1 mutations, MSI-H) was found in tumors from The Cancer Genome Atlas. Conclusion POLD1 mutation with associated MSI-H and hyper-indel–hypermutated cancer genome characterizes a previously unrecognized variant of colon cancer that was found in this patient with an exceptional response to chemotherapy.

Genome-wide methylation and expression profiling identify methylation-associated genes in colorectal cancer

Epigenomics ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 19-36 ◽  
Author(s):  
Xiaohui Sun ◽  
Diyu Chen ◽  
Ziqi Jin ◽  
Tianhui Chen ◽  
Aifen Lin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Expression Profiling ◽  
The Cancer Genome Atlas ◽  
Gene Overexpression ◽  
Normal Tissues ◽  
Atlas Data ◽  
Genome Wide ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Aim: To identify methylation-associated genes in the carcinogenesis of colorectal cancer (CRC). Materials & methods: Genome-wide patterns of DNA methylation and gene expression in CRC tissues and adjacent normal tissues were determined and further validated in The Cancer Genome Atlas data and Chinese CRC patients, respectively. Gene overexpression and knockdown cells were constructed to investigate their biological roles in CRC. Results: After validations, hypermethylation of eight genes were found to be correlated with their reduced transcription, and hypomethyaltion of three genes were associated with their upregulation. CADM3, CNRIP1, GRHL2, GRIA4, GSTM2 and NRXN1 were associated with the overall survival of CRC patients. CNRIP1 and GSTM2 were mainly responsible for the proliferation in CRC cells. Conclusion: A total of 11 genes may be promising biomarkers for CRC.

scholarly journals ECM–Receptor Regulatory Network and Its Prognostic Role in Colorectal Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Stepan Nersisyan ◽  
Victor Novosad ◽  
Narek Engibaryan ◽  
Yuri Ushkaryov ◽  
Sergey Nikulin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Regulatory Network ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Receptor Interaction ◽  
Survival Prediction ◽  
Concordance Index ◽  
Logrank Test ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Interactions of the extracellular matrix (ECM) and cellular receptors constitute one of the crucial pathways involved in colorectal cancer progression and metastasis. With the use of bioinformatics analysis, we comprehensively evaluated the prognostic information concentrated in the genes from this pathway. First, we constructed a ECM–receptor regulatory network by integrating the transcription factor (TF) and 5’-isomiR interaction databases with mRNA/miRNA-seq data from The Cancer Genome Atlas Colon Adenocarcinoma (TCGA-COAD). Notably, one-third of interactions mediated by 5’-isomiRs was represented by noncanonical isomiRs (isomiRs, whose 5’-end sequence did not match with the canonical miRBase version). Then, exhaustive search-based feature selection was used to fit prognostic signatures composed of nodes from the network for overall survival prediction. Two reliable prognostic signatures were identified and validated on the independent The Cancer Genome Atlas Rectum Adenocarcinoma (TCGA-READ) cohort. The first signature was made up by six genes, directly involved in ECM–receptor interaction: AGRN, DAG1, FN1, ITGA5, THBS3, and TNC (concordance index 0.61, logrank test p = 0.0164, 3-years ROC AUC = 0.68). The second hybrid signature was composed of three regulators: hsa-miR-32-5p, NR1H2, and SNAI1 (concordance index 0.64, logrank test p = 0.0229, 3-years ROC AUC = 0.71). While hsa-miR-32-5p exclusively regulated ECM-related genes (COL1A2 and ITGA5), NR1H2 and SNAI1 also targeted other pathways (adhesion, cell cycle, and cell division). Concordant distributions of the respective risk scores across four stages of colorectal cancer and adjacent normal mucosa additionally confirmed reliability of the models.

scholarly journals Trophinin Is an Important Biomarker and Prognostic Factor in Osteosarcoma: Data Mining from Oncomine and the Cancer Genome Atlas Databases

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Pan Cai ◽  
Yan Lu ◽  
Zhifeng Yin ◽  
Xiuhui Wang ◽  
Xiaoxiao Zhou ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factor ◽  
Prognostic Significance ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Osteosarcoma Cell ◽  
Online Tool ◽  
Potential Biomarker ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Osteosarcoma (OS) is a type of bone malignancy with a high rate of treatment failure. To date, few evident biomarkers for the prognostic significance of OS have been established. Oncomine was used to integrate RNA and DNA-seq data from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and the published literature. The correlation of the gene Trophinin (TRO) and different types of cancers was generated using the Cancer Cell Line Encyclopedia (CCLE) online tool. Prognostic values of featured Melanoma Antigen Gene (MAGE) members were further assessed by establishing the overall survival using the Kaplan-Meier plotter. Moreover, the online tool, Database for Annotation, Visualization and Integrated Discovery version (DAVID), was used to understand the biological meaning list of the genes. MAGEB10, MAGED2, TRO, MAGEH1, MAGEB18, MAGEB6, MAGEB4, MAGEB1, MAGED4B, MAGED1, MAGEB2, and MAGEB3 were significantly overexpressed in sarcoma. TRO was further demonstrated to be distinctively upregulated in osteosarcoma cell lines and associated with shorter overall survival. TRO may play an important role in the development of OS and may be a promising potential biomarker and prognostic factor.

scholarly journals Glutamyl-Prolyl tRNA Synthetase mRNA is Highly Expressed in Hepatocellular Carcinoma and May be Associated with Poor Prognosis

2021 ◽  
Author(s):  
Jinyong Shu ◽  
Yi Gao ◽  
Guifeng Zhang ◽  
Pan Luo
Keyword(s):  
Hepatocellular Carcinoma ◽  
Histological Grade ◽  
Mrna Level ◽  
Trna Synthetase ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Poor Overall Survival ◽  
Normal Tissues ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Abstract BackgroundAlthough glutamyl-prolyl tRNA synthetase (EPRS) mRNA is overexpressed and plays an important role in most tumors, its role in the development and progression of hepatocellular carcinoma (HCC) remains unclear. MethodsThe expression of EPRS in tumor and adjacent tissues was queried using TIMER and The Cancer Genome Atlas. The results were validated using the real-time reverse transcription polymerase chain reaction on RNA extracted from tumor and adjacent non-tumor samples from 10 HCC patients.ResultsUsing bioinformatics analysis, we found that EPRS mRNA was overexpressed in HCC tumor tissues, and the expression level of EPRS mRNA in The Cancer Genome Atlas database was significantly correlated with tumor size (p = 0.0010), histological grade (p = 0.0002), TNM stage (p = 0.0001), and vascular invasion (p = 0.0123) of HCC. The Kaplan-Meier survival analysis demonstrated that the expression of EPRS mRNA was associated with poor overall survival (p = 0.0004). Ten pairs of tumor and adjacent normal tissues were collected from patients with HCC, and the expression of EPRS mRNA was verified. The results showed that the EPRS mRNA level in HCC tissues was higher than that in paracancerous tissues (p = 0.0401). ConclusionOverexpression of EPRS mRNA may be associated with tumorigenesis and the progression of HCC.

KRAB ZNF explorer—the online tool for the exploration of the transcriptomic profiles of KRAB-ZNF factors in The Cancer Genome Atlas

2019 ◽  
Author(s):  
Rafał Cylwa ◽  
Kornel Kiełczewski ◽  
Marta Machnik ◽  
Urszula Oleksiewicz ◽  
Przemysław Biecek
Keyword(s):  
Zinc Finger Protein ◽  
Methylation Status ◽  
Source Code ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Web Based ◽  
Normal Tissues ◽  
Cancer Genome Atlas ◽  
Cancer Tissues ◽  
Genome Atlas

Abstract Summary Krüppel-associated box domain zinc finger protein (KRAB ZNF) explorer is a web-based tool for comprehensive characterization of the mRNA expression status of KRAB-ZNF transcription factors in the data from The Cancer Genome Atlas study. Key functionalities cover a comparative analysis of KRAB-ZNF expression between normal and cancer tissues, an association of KRAB-ZNF expression with various pathological features, including survival analysis, association with global DNA methylation status, analyses of KRAB-ZNF isoform expressions and analysis of KRAB-ZNF levels in normal tissues. Availability and implementation KRAB ZNF explorer is available at http://mi2.mini.pw.edu.pl: 8080/KRAB_ZNF/. The source code for shiny application is available at: https://github.com/MI2DataLab/KRAB_ZNF/tree/master/app and the source code for analyses and precalculations are available at: https://github.com/MI2DataLab/KRAB_ZNF/tree/master/work

scholarly journals Downregulation of SPINK13 Promotes Metastasis by Regulating uPA in Ovarian Cancer Cells

2018 ◽  
Vol 45 (3) ◽  
pp. 1061-1071 ◽  
Author(s):  
Shengyun Cai ◽  
Pei Zhang ◽  
Suhe Dong ◽  
Li Li ◽  
Jianming Cai ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Regression Analysis ◽  
Cellular Proliferation ◽  
Cox Regression ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Cox Regression Analysis ◽  
Normal Tissues ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Background/Aims: Ovarian cancer (OC) is the fifth leading cause of cancer-related death in women, and it is difficult to diagnose at an early stage. The purpose of this study was to explore the prognostic biological markers of OC. Methods: Univariate Cox regression analysis was used to identify genes related to OC prognosis from the Cancer Genome Atlas(TCGA) database. Immunohistochemistry was used to analyse the level of SPINK13 in OC and normal tissues. Cell proliferation, apoptosis and invasion were performed using MTT assay, flow cytometric analysis and Transwell assay, respectively. Results: We identified the Kazal-type serine protease inhibitor-13 (SPINK13) gene related to OC prognosis from the Cancer Genome Atlas (TCGA) database by univariate Cox regression analysis. Overexpression of SPINK13 was associated with higher overall survival rate in OC patients. Immunohistochemistry showed that the level of SPINK13 protein was significantly lower in OC tissues than in normal tissues (P < 0.05).In vitro experiments showed that the overexpression of SPINK13 inhibited cellular proliferation and promoted apoptosis. Moreover, SPINK13 inhibited cell migration and epithelial to mesenchymal transition (EMT). SPINK13 was found to inhibit the expression of urokinase-type plasminogen activator (uPA), while recombinant uPA protein could reverse the inhibitory effect of SPINK13 on OC metastasis. Conclusion: These results indicate that SPINK13 functions as a tumour suppressor. The role of SPINK13 in cellular proliferation, apoptosis and migration is uPA dependent, and SPINK13 may be used as a potential biomarker for diagnosis and targeted therapy in OC.

scholarly journals Association Between Obesity and Incident Colorectal Cancer: An Analysis Based on Colorectal Cancer Database in the Cancer Genome Atlas

2021 ◽  
Author(s):  
Su Yongxian ◽  
Chen Tonghua
Keyword(s):  
Colorectal Cancer ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Obese Group ◽  
Pathway Enrichment Analysis ◽  
Ppi Network ◽  
Hub Genes ◽  
Significant Difference ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Abstract Background To investigate gene factors of colorectal cancer (CRC) in obesity and potential molecular markers. Methods Clinical data and mRNA expression data from The Cancer Genome Atlas (TCGA) was collected and divided into obese group and non-obese group according to BMI. The differential expressed genes (DEGs) were screened out by “Limma” package of R software based on (|log2(fold change)|>2 and p < 0.05). The functions of DEGs were revealed with Gene Ontology and Kyoto Encyclopedia Genes and Genomes pathway enrichment analysis using the DAVID database. Then STRING database and Cytoscape were used to construct a protein-protein interaction (PPI) network and identify hub genes. Kaplan-Meier analysis was used to assess the potential prognostic genes for CRC patients. Results It has revealed 2055 DEGs in obese group with CRC, 7615 DEGs in non-obese group and 9046 DEGs in total group. MS4A12, TMIGD1, CA2, GBA3 and SLC51B were the top five downregulated genes in obese group. A PPI network consisted of 1042 nodes and 4073 edges, and top ten hub genes SST, PYY, GNG12, CCL13, MCHR2, CCL28, ADCY9, SSTR1, CXCL12 and ADRA2A were identified in obese group. PDCD11 may well predict overall survivals of CRC patients in non-obese group. The survival time of obese group was shorter than that of non-obese group, but there was no significant difference. Conclusions PDCD11 may be a potential molecular marker for non-obese patients with CRC.

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