scholarly journals Genes with Relevance for Early to Late Progression of Colon Carcinoma Based on Combined Genomic and Transcriptomic Information from the Same Patients

2010 ◽  
Vol 9 ◽  
pp. CIN.S4545 ◽  
Author(s):  
Kristina K. Lagerstedt ◽  
Erik Kristiansson ◽  
Christina Lönnroth ◽  
Marianne Andersson ◽  
Britt-Marie IresjÖ ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colon Cancer ◽  
Tumor Progression ◽  
Cancer Progression ◽  
Copy Number ◽  
Dna Copy Number ◽  
Colon Cancer Progression ◽  
Dna Alterations ◽  
Copy Number Changes ◽  
Dukes C

Background Genetic and epigenetic alterations in colorectal cancer are numerous. However, it is difficult to judge whether such changes are primary or secondary to the appearance and progression of tumors. Therefore, the aim of the present study was to identify altered DNA regions with significant covariation to transcription alterations along colon cancer progression. Methods Tumor and normal colon tissue were obtained at primary operations from 24 patients selected by chance. DNA, RNA and microRNAs were extracted from the same biopsy material in all individuals and analyzed by oligo-nucleotide array-based comparative genomic hybridization (CGH), mRNA- and microRNA oligo-arrays. Statistical analyses were performed to assess statistical interactions (correlations, co-variations) between DNA copy number changes and significant alterations in gene and microRNA expression using appropriate parametric and non-parametric statistics. Results Main DNA alterations were located on chromosome 7, 8, 13 and 20. Tumor DNA copy number gain increased with tumor progression, significantly related to increased gene expression. Copy number loss was not observed in Dukes A tumors. There was no significant relationship between expressed genes and tumor progression across Dukes A–D tumors; and no relationship between tumor stage and the number of microRNAs with significantly altered expression. Interaction analyses identified overall 41 genes, which discriminated early Dukes A plus B tumors from late Dukes C plus D tumor; 28 of these genes remained with correlations between genomic and transcriptomic alterations in Dukes C plus D tumors and 17 in Dukes D. One microRNA (microR-663) showed interactions with DNA alterations in all Dukes A-D tumors. Conclusions Our modeling confirms that colon cancer progression is related to genomic instability and altered gene expression. However, early invasive tumor growth seemed rather related to transcriptomic alterations, where changes in microRNA may be an early phenomenon, and less to DNA copy number changes.

scholarly journals Combined analysis of chromosomal instabilities and gene expression for colon cancer progression inference

2014 ◽  
Vol 4 (1) ◽  
pp. 2 ◽  
Author(s):  
Claudia Cava ◽  
Italo Zoppis ◽  
Manuela Gariboldi ◽  
Isabella Castiglioni ◽  
Giancarlo Mauri ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colon Cancer ◽  
Cancer Progression ◽  
Combined Analysis ◽  
Colon Cancer Progression ◽  
Chromosomal Instabilities

Peroxireduxin-4 is Over-Expressed in Colon Cancer and its Down-Regulation Leads to Apoptosis

2011 ◽  
Vol 4 ◽  
pp. CGM.S6584 ◽  
Author(s):  
Sandra M. Leydold ◽  
Michael Seewald ◽  
Christian Stratowa ◽  
Klaus Kaserer ◽  
Wolfgang Sommergruber ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colon Cancer ◽  
Cancer Progression ◽  
Expression Patterns ◽  
Morphological Characteristics ◽  
Normal Colon ◽  
Primary Tumors ◽  
Colon Cancer Progression ◽  
Primary Colon ◽  
Insight Into

The objective of this study was to gain insight into the biological basis of colon cancer progression by characterizing gene expression differences between normal colon epithelium, corresponding colorectal primary tumors and metastases. We found a close similarity in gene expression patterns between primary tumors and metastases, indicating a correlation between gene expression and morphological characteristics. PRDX4 was identified as highly expressed both in primary colon tumors and metastases, and selected for further characterization. Our study revealed that “Prdx4” (PrxIV, AOE372) shows functional similarities to other Prx family members by negatively affecting apoptosis induction in tumor cells. In addition, our study links Prdx4 with Hif-1α, a key regulatory factor of angiogenesis. Targeting Prdx4 may be an attractive approach in cancer therapy, as its inhibition is expected to lead to induction of apoptosis and blockage of Hif-1α-mediated tumor angiogenesis.

scholarly journals RBMS1 suppresses colon cancer metastasis through targeted stabilization of its mRNA regulon

2020 ◽  
Author(s):  
Johnny Yu ◽  
Bruce Culbertson ◽  
Hosseinali Asgharian ◽  
Albertas Navickas ◽  
Lisa Fish ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colon Cancer ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Rna Binding ◽  
Rna Stability ◽  
Transcriptional Regulator ◽  
Clinical Samples ◽  
Colon Cancer Metastasis ◽  
Colon Cancer Progression

AbstractBroad dysregulation of gene expression control is a hallmark of cancer progression. Identifying the underlying master regulators that drive pathological gene expression is a key challenge in precision oncology. Here, we have developed a network analytical framework, named PRADA, that identifies oncogenic RNA-binding proteins through the systematic detection of coordinated changes in their target regulons. Application of this approach to data collected from clinical samples, patient-derived xenografts, and cell line models of colon cancer metastasis revealed the RNA-binding protein RBMS1 as a suppressor of colon cancer progression. We observed that silencing RBMS1 results in increased metastatic capacity in xenograft mouse models, and that restoring its expression blunts metastatic liver colonization. We have found that RBMS1 functions as a post-transcriptional regulator of RNA stability by directly binding and stabilizing ~80 target mRNAs. Measurements in more than 180 clinical samples as well as survival analyses in publicly available datasets, have shown that RBMS1 silencing and the subsequent downregulation of its targets are strongly associated with disease progression and poor survival in colon cancer patients. Together, our findings establish a role for RBMS1 as a previously unknown regulator of RNA stability and as a suppressor of colon cancer metastasis with clinical utility for risk stratification of patients.SignificanceBy applying a new analytical approach to transcriptomic data from clinical samples and models of colon cancer progression, we have uncovered RBMS1 as a suppressor of metastasis and as a post-transcriptional regulator of RNA stability. Notably, RBMS1 silencing and downregulation of its targets are negatively associated with patient survival.

scholarly journals An Integrated Approach for RNA-seq Data Normalization

2016 ◽  
Vol 15 ◽  
pp. CIN.S39781 ◽  
Author(s):  
Shengping Yang ◽  
Donald E. Mercante ◽  
Kun Zhang ◽  
Zhide Fang
Keyword(s):  
Gene Expression ◽  
Dna Sequences ◽  
Copy Number ◽  
Differentially Expressed Gene ◽  
Integrated Approach ◽  
Gene Profiling ◽  
Data Normalization ◽  
Rna Seq ◽  
Dna Copy Number ◽  
Copy Number Changes

Background DNA copy number alteration is common in many cancers. Studies have shown that insertion or deletion of DNA sequences can directly alter gene expression, and significant correlation exists between DNA copy number and gene expression. Data normalization is a critical step in the analysis of gene expression generated by RNA-seq technology. Successful normalization reduces/removes unwanted nonbiological variations in the data, while keeping meaningful information intact. However, as far as we know, no attempt has been made to adjust for the variation due to DNA copy number changes in RNA-seq data normalization. Results In this article, we propose an integrated approach for RNA-seq data normalization. Comparisons show that the proposed normalization can improve power for downstream differentially expressed gene detection and generate more biologically meaningful results in gene profiling. In addition, our findings show that due to the effects of copy number changes, some housekeeping genes are not always suitable internal controls for studying gene expression. Conclusions Using information from DNA copy number, integrated approach is successful in reducing noises due to both biological and nonbiological causes in RNA-seq data, thus increasing the accuracy of gene profiling.

AML/MDS with 11q/MLLamplification show characteristic gene expression signature and interplay of DNA copy number changes

2009 ◽  
Vol 48 (6) ◽  
pp. 510-520 ◽  
Author(s):  
Andrea Zatkova ◽  
Sylvia Merk ◽  
Melanie Wendehack ◽  
Martin Bilban ◽  
Eva Maria Muzik ◽  
...  
Keyword(s):  
Gene Expression ◽  
Copy Number ◽  
Gene Expression Signature ◽  
Dna Copy Number ◽  
Expression Signature ◽  
Copy Number Changes
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