For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
4
views
40
references
 Top references
cited by
1
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      152
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Transcriptome of sessile serrated adenoma/polyps is associated with MSI‐high colorectal cancer and decreased expression of CDX2

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The objective of this study was to elucidate the molecular background of sessile serrated adenoma/polyp (SSA/P) endoscopically resected with comprehensive gene expression analysis. Gene expression profiling was performed for 10 tumor‐normal pairs of SSA/P. Cluster analysis, gene set enrichment analysis (GSEA), and consensus molecular subtype (CMS) classification of colorectal cancer (CRC) were applied to our transcriptome analysis. Unsupervised cluster analysis showed that the gene expression profile of SSA/Ps is different from that of adjacent normal epithelial cells, even in the very early stage of tumorigenesis. According to the CMS classification, our microarray data indicated that SSA/Ps were classified as CMS1. GSEA demonstrated a strong association between SSA/P and microsatellite instability‐high (MSI‐H) CRC ( p < 10 −5). Transcriptome analysis of five MSI‐related genes ( MSH2, MSH6, MLH1, PMS1, and PMS2) and five CRC‐related genes ( BRAF, KRAS, APC, TP53, and CDX2) showed that CDX2 expression was most severely decreased in SSA/P. Immunohistochemical staining confirmed that CDX2 protein was reduced compared with the surrounding mucosa. Direct sequencing of the BRAF gene showed that the BRAF V600E mutation was detected in only nine of 36 cases. In a mouse model, BRAF, APC, or CDX2 deficiency indicated that the gene expression pattern with loss of CDX2 is more similar to our SSA/Ps compared with those induced by BRAF or APC mutation. Transcriptome analysis of SSA/Ps showed characteristic gene expression with a strong resemblance to MSI‐H CRC. Downregulation of CDX2 expression is an essential molecular mechanism involved in the initial stage of SSA/P tumorigenesis. (UMIN000027365).

          Abstract

          SSA/Ps showed characteristic gene expression with a strong resemblance to microsatellite instability‐high colorectal cancer. And the downregulation of CDX2 expression is an essential molecular mechanism involved in the initial stage of SSA/P tumorigenesis.

          Related collections

          Most cited references40

          • Record: found
          • Abstract: found
          • Article: not found

          Cancer Statistics, 2021

          Rebecca Siegel, Kimberly D Miller, Hannah Fuchs … (2021)
          Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence. Incidence data (through 2017) were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2018) were collected by the National Center for Health Statistics. In 2021, 1,898,160 new cancer cases and 608,570 cancer deaths are projected to occur in the United States. After increasing for most of the 20th century, the cancer death rate has fallen continuously from its peak in 1991 through 2018, for a total decline of 31%, because of reductions in smoking and improvements in early detection and treatment. This translates to 3.2 million fewer cancer deaths than would have occurred if peak rates had persisted. Long-term declines in mortality for the 4 leading cancers have halted for prostate cancer and slowed for breast and colorectal cancers, but accelerated for lung cancer, which accounted for almost one-half of the total mortality decline from 2014 to 2018. The pace of the annual decline in lung cancer mortality doubled from 3.1% during 2009 through 2013 to 5.5% during 2014 through 2018 in men, from 1.8% to 4.4% in women, and from 2.4% to 5% overall. This trend coincides with steady declines in incidence (2.2%-2.3%) but rapid gains in survival specifically for nonsmall cell lung cancer (NSCLC). For example, NSCLC 2-year relative survival increased from 34% for persons diagnosed during 2009 through 2010 to 42% during 2015 through 2016, including absolute increases of 5% to 6% for every stage of diagnosis; survival for small cell lung cancer remained at 14% to 15%. Improved treatment accelerated progress against lung cancer and drove a record drop in overall cancer mortality, despite slowing momentum for other common cancers.
          Article 0 comments Cited 6868 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The Consensus Molecular Subtypes of Colorectal Cancer

            Justin Guinney, Rodrigo Dienstmann, Xin Ke Wang … (2015)
            Colorectal cancer (CRC) is a frequently lethal disease with heterogeneous outcomes and drug responses. To resolve inconsistencies among the reported gene expression–based CRC classifications and facilitate clinical translation, we formed an international consortium dedicated to large-scale data sharing and analytics across expert groups. We show marked interconnectivity between six independent classification systems coalescing into four consensus molecular subtypes (CMS) with distinguishing features: CMS1 (MSI Immune, 14%), hypermutated, microsatellite unstable, strong immune activation; CMS2 (Canonical, 37%), epithelial, chromosomally unstable, marked WNT and MYC signaling activation; CMS3 (Metabolic, 13%), epithelial, evident metabolic dysregulation; and CMS4 (Mesenchymal, 23%), prominent transforming growth factor β activation, stromal invasion, and angiogenesis. Samples with mixed features (13%) possibly represent a transition phenotype or intra-tumoral heterogeneity. We consider the CMS groups the most robust classification system currently available for CRC – with clear biological interpretability – and the basis for future clinical stratification and subtype–based targeted interventions.
            Article 0 comments Cited 1239 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Consensus molecular subtypes and the evolution of precision medicine in colorectal cancer

              Rodrigo Dienstmann, Louis Vermeulen, Justin Guinney … (2017)
              In this Review, Dienstmann et al. analyse the complex nature of colorectal cancer and the different subtypes in which this disease can be classified, advocating for a 'multi-molecular' perspective for the development of therapies to treat it.
              Article 0 comments Cited 327 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Contributors
                Nobutake Yamamichi:
                ORCID: https://orcid.org/0000-0002-5741-9887
                nobutakeyamamichi@gmail.com
                Journal
                Journal ID (nlm-ta): Cancer Med
                Journal ID (iso-abbrev): Cancer Med
                Journal ID (doi): 10.1002/(ISSN)2045-7634
                Journal ID (publisher-id): CAM4
                Title: Cancer Medicine
                Publisher: John Wiley and Sons Inc. (Hoboken )
                ISSN (Electronic): 2045-7634
                Publication date (Electronic): 10 May 2022
                Publication date Collection: December 2022
                Volume: 11
                Issue: 24 ( doiID: 10.1002/cam4.v11.24 )
                Pages: 5066-5078
                Affiliations
                [ 1 ] Department of Gastroenterology, Graduate School of Medicine The University of Tokyo Tokyo Japan
                [ 2 ] Department of Joint Research Laboratory of Clinical Medicine Fujita Health University School of Medicine Aichi Japan
                [ 3 ] Center for Comprehensive Genomic Medicine Okayama University Hospital Okayama Japan
                Author notes
                [*] [* ] Correspondence

                Nobutake Yamamichi, Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7‐3‐1 Hongo, Bunkyo‐ku, Tokyo 113‐8655, Japan.

                Email: nobutakeyamamichi@ 123456gmail.com

                Author information
                https://orcid.org/0000-0002-5741-9887
                Article
                Publisher ID: CAM44810 Other ID: CAM4-2022-03-1083.R3
                DOI: 10.1002/cam4.4810
                PMC ID: 9761061
                PubMed ID: 35535692
                SO-VID: e189c533-0c51-4890-8df9-472063e694c4
                Copyright © © 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
                License:

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                Date revision received : 21 April 2022
                Date received : 18 March 2022
                Date accepted : 25 April 2022
                Page count
                Figures: 6, Tables: 2, Pages: 13, Words: 6111
                Funding
                Funded by: JSPS KAKENHI
                Award ID: JP20K16980
                Categories
                Subject: Research Article
                Subject: Research Articles
                Subject: Bioinformatics
                Custom metadata
                source-schema-version-number 2.0
                cover-date December 2022
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:6.2.3 mode:remove_FC converted:19.12.2022

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: cdx2,comprehensive gene expression analysis,microsatellite instability‐high colorectal cancer,sessile serrated adenoma/polyp,transcriptome analysis
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: cdx2, comprehensive gene expression analysis, microsatellite instability‐high colorectal cancer, sessile serrated adenoma/polyp, transcriptome analysis

                Comments

                Comment on this article