Deep Sequencing the MicroRNA Transcriptome in Colorectal Cancer
Publication Date
June 18, 2013
Journal
PLOS ONE
Authors
Kristina Schee, Susanne Lorenz, Merete Molton Worren, Clara Cecilie Günther, et al
Volume
8
Issue
6
Pages
e66165
DOI
https://dx.plos.org/10.1371/journal.pone.0066165
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0066165
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/23824282
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3688869
Europe PMC
http://europepmc.org/abstract/MED/23824282
Web of Science
000320576400062
Scopus
84879174920
Mendeley
http://www.mendeley.com/research/deep-sequencing-microrna-transcriptome-colorectal-cancer
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Mendeley | Further Information

{"title"=>"Deep Sequencing the MicroRNA Transcriptome in Colorectal Cancer", "type"=>"journal", "authors"=>[{"first_name"=>"Kristina", "last_name"=>"Schee", "scopus_author_id"=>"36524014200"}, {"first_name"=>"Susanne", "last_name"=>"Lorenz", "scopus_author_id"=>"55266491400"}, {"first_name"=>"Merete Molton", "last_name"=>"Worren", "scopus_author_id"=>"55769417300"}, {"first_name"=>"Clara Cecilie", "last_name"=>"Günther", "scopus_author_id"=>"55769283500"}, {"first_name"=>"Marit", "last_name"=>"Holden", "scopus_author_id"=>"7102163440"}, {"first_name"=>"Eivind", "last_name"=>"Hovig", "scopus_author_id"=>"7004194119"}, {"first_name"=>"Øystein", "last_name"=>"Fodstad", "scopus_author_id"=>"7006432621"}, {"first_name"=>"Leonardo A.", "last_name"=>"Meza-Zepeda", "scopus_author_id"=>"6602589294"}, {"first_name"=>"Kjersti", "last_name"=>"Flatmark", "scopus_author_id"=>"6603644461"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"369142296", "sgr"=>"84879174920", "issn"=>"19326203", "pmid"=>"23824282", "scopus"=>"2-s2.0-84879174920", "doi"=>"10.1371/journal.pone.0066165", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)"}, "id"=>"0611acc7-de3b-3301-8cb4-74bf15e0284e", "abstract"=>"Colorectal cancer (CRC) is one of the leading causes of cancer related deaths and the search for prognostic biomarkers that might improve treatment decisions is warranted. MicroRNAs (miRNAs) are short non-coding RNA molecules involved in regulating gene expression and have been proposed as possible biomarkers in CRC. In order to characterize the miRNA transcriptome, a large cohort including 88 CRC tumors with long-term follow-up was deep sequenced. 523 mature miRNAs were expressed in our cohort, and they exhibited largely uniform expression patterns across tumor samples. Few associations were found between clinical parameters and miRNA expression, among them, low expression of miR-592 and high expression of miR-10b-5p and miR-615-3p were associated with tumors located in the right colon relative to the left colon and rectum. High expression of miR-615-3p was also associated with poorly differentiated tumors. No prognostic biomarker candidates for overall and metastasis-free survival were identified by applying the LASSO method in a Cox proportional hazards model or univariate Cox. Examination of the five most abundantly expressed miRNAs in the cohort (miR-10a-5p, miR-21-5p, miR-22-3p, miR-143-3p and miR-192-5p) revealed that their collective expression represented 54% of the detected miRNA sequences. Pathway analysis of the target genes regulated by the five most highly expressed miRNAs uncovered a significant number of genes involved in the CRC pathway, including APC, TGFβ and PI3K, thus suggesting that these miRNAs are relevant in CRC.", "link"=>"http://www.mendeley.com/research/deep-sequencing-microrna-transcriptome-colorectal-cancer", "reader_count"=>79, "reader_count_by_academic_status"=>{"Unspecified"=>4, "Professor > Associate Professor"=>3, "Student > Doctoral Student"=>4, "Researcher"=>18, "Student > Ph. D. Student"=>19, "Student > Postgraduate"=>2, "Student > Master"=>22, "Other"=>1, "Student > Bachelor"=>6}, "reader_count_by_user_role"=>{"Unspecified"=>4, "Professor > Associate Professor"=>3, "Student > Doctoral Student"=>4, "Researcher"=>18, "Student > Ph. D. Student"=>19, "Student > Postgraduate"=>2, "Student > Master"=>22, "Other"=>1, "Student > Bachelor"=>6}, "reader_count_by_subject_area"=>{"Unspecified"=>6, "Biochemistry, Genetics and Molecular Biology"=>15, "Agricultural and Biological Sciences"=>44, "Medicine and Dentistry"=>9, "Neuroscience"=>1, "Computer Science"=>1, "Immunology and Microbiology"=>3}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>9}, "Neuroscience"=>{"Neuroscience"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>44}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>15}, "Unspecified"=>{"Unspecified"=>6}}, "reader_count_by_country"=>{"Brazil"=>1, "South Africa"=>1, "Italy"=>1, "Malaysia"=>1, "India"=>2}, "group_count"=>3}

CrossRef

Scopus | Further Information

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Figshare

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  • {"files"=>["https://ndownloader.figshare.com/files/1091456"], "description"=>"<p>High expression of miR-10b-5p and miR-615-3p and low expression of miR-592 were associated with tumor localized in the right colon relative to the left colon and rectum (q <0.001 and p<0.001).</p>", "links"=>[], "tags"=>["Biochemistry", "Nucleic acids", "rna", "genomics", "Genome sequencing", "Diagnostic medicine", "pathology", "General pathology", "biomarkers", "Gastroenterology and hepatology", "Gastrointestinal cancers", "oncology", "Cancers and neoplasms", "Gastrointestinal tumors", "Rectal cancer", "mir-615-3p", "mir-592"], "article_id"=>723916, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Kristina Schee", "Susanne Lorenz", "Merete Molton Worren", "Clara-Cecilie Günther", "Marit Holden", "Eivind Hovig", "Øystein Fodstad", "Leonardo A. Meza-Zepeda", "Kjersti Flatmark"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066165.g008", "stats"=>{"downloads"=>2, "page_views"=>36, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Boxplot_of_miR_10b_5p_miR_615_3p_and_miR_592_and_tumor_localization_/723916", "title"=>"Boxplot of miR-10b-5p, miR-615-3p and miR-592 and tumor localization.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-18 01:05:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/1091452"], "description"=>"<p>The normalized expression values were log2 transformed and analyzed by unsupervised two-way hierarchical clustering using weighted average linkage (WPGMA). The global map contains all expressed miRNAs shown vertically and the patient samples horizontally.</p>", "links"=>[], "tags"=>["Biochemistry", "Nucleic acids", "rna", "genomics", "Genome sequencing", "Diagnostic medicine", "pathology", "General pathology", "biomarkers", "Gastroenterology and hepatology", "Gastrointestinal cancers", "oncology", "Cancers and neoplasms", "Gastrointestinal tumors", "Rectal cancer", "clustering", "mirna", "crc"], "article_id"=>723912, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Kristina Schee", "Susanne Lorenz", "Merete Molton Worren", "Clara-Cecilie Günther", "Marit Holden", "Eivind Hovig", "Øystein Fodstad", "Leonardo A. Meza-Zepeda", "Kjersti Flatmark"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066165.g006", "stats"=>{"downloads"=>3, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Hierarchical_clustering_of_miRNA_expression_levels_in_the_CRC_cohort_/723912", "title"=>"Hierarchical clustering of miRNA expression levels in the CRC cohort.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-18 01:05:12"}
  • {"files"=>["https://ndownloader.figshare.com/files/1091446"], "description"=>"<p>Differential expression of the five most abundantly expressed miRNAs in our CRC cohort. The total numbers of miRNA reads are log2 transformed. The circles represent outliers and the stars represent extreme outliers.</p>", "links"=>[], "tags"=>["Biochemistry", "Nucleic acids", "rna", "genomics", "Genome sequencing", "Diagnostic medicine", "pathology", "General pathology", "biomarkers", "Gastroenterology and hepatology", "Gastrointestinal cancers", "oncology", "Cancers and neoplasms", "Gastrointestinal tumors", "Rectal cancer"], "article_id"=>723906, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Kristina Schee", "Susanne Lorenz", "Merete Molton Worren", "Clara-Cecilie Günther", "Marit Holden", "Eivind Hovig", "Øystein Fodstad", "Leonardo A. Meza-Zepeda", "Kjersti Flatmark"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066165.g003", "stats"=>{"downloads"=>2, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Boxplot_of_the_five_most_highly_expressed_miRNAs_/723906", "title"=>"Boxplot of the five most highly expressed miRNAs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-18 01:05:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/1091459"], "description"=>"<p>Clinical and histopathological characteristics of the investigated patient cohort (n = 88).</p>", "links"=>[], "tags"=>["Biochemistry", "Nucleic acids", "rna", "genomics", "Genome sequencing", "Diagnostic medicine", "pathology", "General pathology", "biomarkers", "Gastroenterology and hepatology", "Gastrointestinal cancers", "oncology", "Cancers and neoplasms", "Gastrointestinal tumors", "Rectal cancer", "histopathological", "investigated", "cohort"], "article_id"=>723919, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Kristina Schee", "Susanne Lorenz", "Merete Molton Worren", "Clara-Cecilie Günther", "Marit Holden", "Eivind Hovig", "Øystein Fodstad", "Leonardo A. Meza-Zepeda", "Kjersti Flatmark"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066165.t001", "stats"=>{"downloads"=>6, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Clinical_and_histopathological_characteristics_of_the_investigated_patient_cohort_n_8202_8202_88_/723919", "title"=>"Clinical and histopathological characteristics of the investigated patient cohort (n = 88).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-06-18 01:05:19"}
  • {"files"=>["https://ndownloader.figshare.com/files/1091460"], "description"=>"<div><p>Colorectal cancer (CRC) is one of the leading causes of cancer related deaths and the search for prognostic biomarkers that might improve treatment decisions is warranted. MicroRNAs (miRNAs) are short non-coding RNA molecules involved in regulating gene expression and have been proposed as possible biomarkers in CRC. In order to characterize the miRNA transcriptome, a large cohort including 88 CRC tumors with long-term follow-up was deep sequenced. 523 mature miRNAs were expressed in our cohort, and they exhibited largely uniform expression patterns across tumor samples. Few associations were found between clinical parameters and miRNA expression, among them, low expression of miR-592 and high expression of miR-10b-5p and miR-615-3p were associated with tumors located in the right colon relative to the left colon and rectum. High expression of miR-615-3p was also associated with poorly differentiated tumors. No prognostic biomarker candidates for overall and metastasis-free survival were identified by applying the LASSO method in a Cox proportional hazards model or univariate Cox. Examination of the five most abundantly expressed miRNAs in the cohort (miR-10a-5p, miR-21-5p, miR-22-3p, miR-143-3p and miR-192-5p) revealed that their collective expression represented 54% of the detected miRNA sequences. Pathway analysis of the target genes regulated by the five most highly expressed miRNAs uncovered a significant number of genes involved in the CRC pathway, including APC, TGFβ and PI3K, thus suggesting that these miRNAs are relevant in CRC.</p></div>", "links"=>[], "tags"=>["Biochemistry", "Nucleic acids", "rna", "genomics", "Genome sequencing", "Diagnostic medicine", "pathology", "General pathology", "biomarkers", "Gastroenterology and hepatology", "Gastrointestinal cancers", "oncology", "Cancers and neoplasms", "Gastrointestinal tumors", "Rectal cancer", "sequencing", "microrna", "transcriptome", "colorectal"], "article_id"=>723920, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Kristina Schee", "Susanne Lorenz", "Merete Molton Worren", "Clara-Cecilie Günther", "Marit Holden", "Eivind Hovig", "Øystein Fodstad", "Leonardo A. Meza-Zepeda", "Kjersti Flatmark"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066165", "stats"=>{"downloads"=>1, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Deep_Sequencing_the_MicroRNA_Transcriptome_in_Colorectal_Cancer_/723920", "title"=>"Deep Sequencing the MicroRNA Transcriptome in Colorectal Cancer", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-06-18 01:05:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/1091458"], "description"=>"<p>Table showing two class unpaired significance analysis with 10000 permutations of the miRNAs which exhibited significant associations with tumor localization and differentiation. FDR: False discovery rate.</p>", "links"=>[], "tags"=>["Biochemistry", "Nucleic acids", "rna", "genomics", "Genome sequencing", "Diagnostic medicine", "pathology", "General pathology", "biomarkers", "Gastroenterology and hepatology", "Gastrointestinal cancers", "oncology", "Cancers and neoplasms", "Gastrointestinal tumors", "Rectal cancer", "localization"], "article_id"=>723918, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Kristina Schee", "Susanne Lorenz", "Merete Molton Worren", "Clara-Cecilie Günther", "Marit Holden", "Eivind Hovig", "Øystein Fodstad", "Leonardo A. Meza-Zepeda", "Kjersti Flatmark"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066165.t003", "stats"=>{"downloads"=>3, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_SAM_analysis_of_tumor_localization_and_differentiation_/723918", "title"=>"SAM analysis of tumor localization and differentiation.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-06-18 01:05:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/1091455"], "description"=>"<p>Expression of six miRNAs (miR-21, miR-31, miR-92a, miR-101, miR-106a and miR-145) is shown from deep sequencing and qRT-PCR for 88 patient samples that were analyzed with both methods. <b>A.</b> The bars represent the sum of the total number of reads (x10<sup>6</sup>) for each miRNA from deep sequencing. <b>B.</b> The bars represent the sum of the relative expression (2<sup>−dCt</sup> ) from qRT-PCR.</p>", "links"=>[], "tags"=>["Biochemistry", "Nucleic acids", "rna", "genomics", "Genome sequencing", "Diagnostic medicine", "pathology", "General pathology", "biomarkers", "Gastroenterology and hepatology", "Gastrointestinal cancers", "oncology", "Cancers and neoplasms", "Gastrointestinal tumors", "Rectal cancer", "mirnas", "sequencing"], "article_id"=>723915, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Kristina Schee", "Susanne Lorenz", "Merete Molton Worren", "Clara-Cecilie Günther", "Marit Holden", "Eivind Hovig", "Øystein Fodstad", "Leonardo A. Meza-Zepeda", "Kjersti Flatmark"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066165.g007", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_of_six_selected_miRNAs_with_deep_sequencing_and_qRT_PCR_/723915", "title"=>"Expression of six selected miRNAs with deep sequencing and qRT-PCR.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-18 01:05:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/1091449"], "description"=>"<p>Pathway analysis results for the target genes of the five most highly expressed miRNAs in the colorectal cancer pathway. The illustration was taken from the KEGG database and the miRNAs were added in blue font to indicate the targets regulated by these miRNAs.</p>", "links"=>[], "tags"=>["Biochemistry", "Nucleic acids", "rna", "genomics", "Genome sequencing", "Diagnostic medicine", "pathology", "General pathology", "biomarkers", "Gastroenterology and hepatology", "Gastrointestinal cancers", "oncology", "Cancers and neoplasms", "Gastrointestinal tumors", "Rectal cancer", "mirnas", "crc"], "article_id"=>723909, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Kristina Schee", "Susanne Lorenz", "Merete Molton Worren", "Clara-Cecilie Günther", "Marit Holden", "Eivind Hovig", "Øystein Fodstad", "Leonardo A. Meza-Zepeda", "Kjersti Flatmark"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066165.g005", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_five_most_highly_expressed_miRNAs_and_the_CRC_pathway_/723909", "title"=>"The five most highly expressed miRNAs and the CRC pathway.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-18 01:05:09"}
  • {"files"=>["https://ndownloader.figshare.com/files/1091448"], "description"=>"<p><b>A.</b> MiR-143-3p is found in the same gene cluster as miR-145-5p on chromosome 5 (positions 148808481-148808586 and 148810209-148810296, respectively). MiR-192-5p is found in the same gene cluster as miR-194-5p on chromosome 11 (positions 64658609-64658718 and 64658827-64658911, respectively). Although the miRNAs in each gene cluster is <10kb apart, co-expression was not observed.</p>", "links"=>[], "tags"=>["Biochemistry", "Nucleic acids", "rna", "genomics", "Genome sequencing", "Diagnostic medicine", "pathology", "General pathology", "biomarkers", "Gastroenterology and hepatology", "Gastrointestinal cancers", "oncology", "Cancers and neoplasms", "Gastrointestinal tumors", "Rectal cancer", "mirnas", "respective"], "article_id"=>723908, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Kristina Schee", "Susanne Lorenz", "Merete Molton Worren", "Clara-Cecilie Günther", "Marit Holden", "Eivind Hovig", "Øystein Fodstad", "Leonardo A. Meza-Zepeda", "Kjersti Flatmark"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066165.g004", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Two_of_the_most_highly_expressed_miRNAs_shown_with_miRNAs_from_their_respective_gene_clusters_/723908", "title"=>"Two of the most highly expressed miRNAs shown with miRNAs from their respective gene clusters.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-18 01:05:08"}
  • {"files"=>["https://ndownloader.figshare.com/files/1091443"], "description"=>"<p><b>A.</b> Comparison of the technical replicates between run 1 and run 2<b>.</b> Each dot represents the total expression of a single miRNA from all the patient samples. The miRNA expression data was normalized and log2 transformed. <b>B.</b> Unnormalized miRNA read counts (log2) for five randomly selected patients. <b>C.</b> Normalized miRNA read counts (log2) for the same five patients as in B.</p>", "links"=>[], "tags"=>["Biochemistry", "Nucleic acids", "rna", "genomics", "Genome sequencing", "Diagnostic medicine", "pathology", "General pathology", "biomarkers", "Gastroenterology and hepatology", "Gastrointestinal cancers", "oncology", "Cancers and neoplasms", "Gastrointestinal tumors", "Rectal cancer", "replicates", "normalization", "mirna"], "article_id"=>723903, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Kristina Schee", "Susanne Lorenz", "Merete Molton Worren", "Clara-Cecilie Günther", "Marit Holden", "Eivind Hovig", "Øystein Fodstad", "Leonardo A. Meza-Zepeda", "Kjersti Flatmark"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066165.g002", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Technical_replicates_and_normalization_of_miRNA_read_counts_/723903", "title"=>"Technical replicates and normalization of miRNA read counts.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-18 01:05:03"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"26", "full-text"=>"34", "pdf"=>"13", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"5"}
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  • {"unique-ip"=>"17", "full-text"=>"15", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2016", "month"=>"8"}
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Relative Metric

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