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  • Li, XingruUmeå universitet,Patologi (author)

A modified protein marker panel to identify four consensus molecular subtypes in colorectal cancer using immunohistochemistry

  • Article/chapterEnglish2021

Publisher, publication year, extent ...

  • Elsevier,2021
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:umu-181731
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-181731URI
  • https://doi.org/10.1016/j.prp.2021.153379DOI

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  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Colorectal cancer (CRC) is a heterogeneous disease with different genetic and molecular backgrounds, leading to a diverse patient prognosis and treatment response. Four consensus molecular subtypes (CMS 1–4) have recently been proposed based on transcriptome profiling. A clinically practical immunohistochemistry (IHC) based CMS classifier consisting of the four markers FRMD6, ZEB1, HTR2B, and CDX2 was then demonstrated. However, the IHC-CMS classifier did not distinguish between CMS2 and CMS3 tumours. In this study, we have applied the proposed transcriptome based and IHC-based CMS classifiers in a CRC cohort of 65 patients and found a concordance of 77.5 %. Further, we modified the IHC-CMS classifier by analysing the differentially expressed genes between CMS2 and CMS3 tumours using RNA-sequencing data from the TCGA dataset. The result showed that WNT signalling was among the most upregulated pathways in CMS2 tumours, and the expression level of CTNNB1 (encoding β-catenin), a WNT pathway hallmark, was significantly upregulated (P = 1.15 × 10−6). We therefore introduced nuclear β-catenin staining to the IHC-CMS classifier. Using the modified classifier in our cohort, we found a 71.4 % concordance between the IHC and RNA-sequencing based CMS classifiers. Moreover, β-catenin staining could classify 16 out of the 19 CMS2/3 tumours into CMS2 or CMS3, thereby showing an 84.2 % concordance with the RNA-sequencing-based classifier. In conclusion, we evaluated CMS classifiers based on transcriptome and IHC analysis. We present a modified IHC panel that categorizes CRC tumours into the four CMS groups. To our knowledge, this is the first study using IHC to identify all four CMS groups.

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Added entries (persons, corporate bodies, meetings, titles ...)

  • Larsson, PärUmeå universitet,Patologi(Swepub:umu)pala0006 (author)
  • Ljuslinder, Ingrid,1968-Umeå universitet,Onkologi(Swepub:umu)inlj0001 (author)
  • Ling, AgnesUmeå universitet,Patologi(Swepub:umu)agslig01 (author)
  • Löfgren Burström, AnnaUmeå universitet,Patologi(Swepub:umu)anlo0002 (author)
  • Zingmark, Carl,1975-Umeå universitet,Patologi(Swepub:umu)cazi0001 (author)
  • Edin, SofiaUmeå universitet,Patologi(Swepub:umu)soed0001 (author)
  • Palmqvist, RichardUmeå universitet,Patologi(Swepub:umu)ripa0001 (author)
  • Umeå universitetPatologi (creator_code:org_t)

Related titles

  • In:Pathology, Research and Practice: Elsevier2200344-03381618-0631

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