uu.seUppsala universitets publikationer
Ändra sökning
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
CDX2: A Prognostic Marker in Metastatic Colorectal Cancer Defining a Better BRAF Mutated and a Worse KRAS Mutated Subgroup
Univ Bergen, Dept Clin Sci, Bergen, Norway.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi. Department of Pathology, Uppsala University Hospital, Uppsala, Sweden.ORCID-id: 0000-0003-2777-8114
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi. Department of Pathology, Uppsala University Hospital, Uppsala, Sweden.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.ORCID-id: 0000-0002-4394-2634
Visa övriga samt affilieringar
2020 (Engelska)Ingår i: Frontiers in Oncology, ISSN 2234-943X, E-ISSN 2234-943X, Vol. 10, artikel-id 8Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background: Survival of metastatic colorectal cancer (mCRC) patients has improved, but mainly for trial patients. New predictive and prognostic biomarkers validated in the general mCRC population are needed. Caudal-type homeobox 2 (CDX2) is an intestine-specific transcription factor with potential prognostic and predictive effect, but the importance in mCRC has not been fully investigated. Methods: Immunohistochemistry analysis of CDX2 was performed in a Scandinavian population-based cohort of mCRC (n = 796). Frequency, clinical and tumor characteristics, response rate, progression-free survival, and overall survival (OS) were estimated. Results: Loss of CDX2 expression was found in 87 (19%) of 452 stained cases, in 53% if BRAF mutated (BRAFmut) and in 9% if KRAS mutated (KRASmut). CDX2 loss was associated with microsatellite instability, BRAFmut, and poor differentiation and inversely associated with KRASmut. Patients with CDX2 loss received less first-line (53 vs. 64%, p = 0.050) and second-line (23 vs. 39%, p = 0.006) chemotherapy and secondary surgery (1 vs. 9%, p = 0.019). Median progression-free survival and OS for patients given first-line combination chemotherapy was 4 and 10 months if CDX2 loss vs. 9 and 24 months if CDX2 expressed (p = 0.001, p < 0.001). Immediate progression on first-line combination chemotherapy was seen in 35% of patients with CDX2 loss vs. 10% if CDX2 expressed (p = 0.003). Median OS in patients with BRAFmut or KRASmut and CDX2 expressed in tumor (both 21 months) was comparable to wild-type patients (27 months). However, if CDX2 loss, median OS was only 8 and 11 months in BRAFmut and KRASmut cases, respectively, and 10 months in double wild-type patients. In multivariate analysis, CDX2 loss (hazard ratio: 1.50, p = 0.027) and BRAFmut (hazard ratio: 1.62, p = 0.012) were independent poor prognostic markers for OS. Conclusion: In a population-based cohort of mCRC patients, CDX2 loss is an independent poor prognostic marker. Expression of CDX2 defines a new subgroup of BRAFmut cases with a much better prognosis. Loss of CDX2 defines a small group of KRASmut cases with a worse prognosis. Patients with CDX2 loss receive less palliative chemotherapy with less benefit and rarely reach secondary surgery.

Ort, förlag, år, upplaga, sidor
FRONTIERS MEDIA SA , 2020. Vol. 10, artikel-id 8
Nyckelord [en]
caudal type homeobox transcription factor, CDX2, colorectal cancer, metastatic disease, stage 4 colorectal cancer, prognosis, population based
Nationell ämneskategori
Cell- och molekylärbiologi
Identifikatorer
URN: urn:nbn:se:uu:diva-407365DOI: 10.3389/fonc.2020.00008ISI: 000517487200001PubMedID: 32117703OAI: oai:DiVA.org:uu-407365DiVA, id: diva2:1427199
Forskningsfinansiär
CancerfondenTillgänglig från: 2020-04-29 Skapad: 2020-04-29 Senast uppdaterad: 2020-04-29Bibliografiskt granskad

Open Access i DiVA

fulltext(1678 kB)9 nedladdningar
Filinformation
Filnamn FULLTEXT01.pdfFilstorlek 1678 kBChecksumma SHA-512
b75b4d6fdec0e59472d130b12dd4a6c5358e78bc7cf61d058fb165d6a0bc927c590ab2f6204f8a4f7578d8d188d7d03ae17cc11c797f7ffdbcaac266e0e99dd3
Typ fulltextMimetyp application/pdf

Övriga länkar

Förlagets fulltextPubMed

Personposter BETA

Dragomir, AncaSundström, MagnusMezheyeuski, ArturEdqvist, Per-Henrik DPontén, FredrikGlimelius, Bengt

Sök vidare i DiVA

Av författaren/redaktören
Dragomir, AncaSundström, MagnusMezheyeuski, ArturEdqvist, Per-Henrik DPontén, FredrikGlimelius, Bengt
Av organisationen
Klinisk och experimentell patologiExperimentell och klinisk onkologiScience for Life Laboratory, SciLifeLab
I samma tidskrift
Frontiers in Oncology
Cell- och molekylärbiologi

Sök vidare utanför DiVA

GoogleGoogle Scholar
Totalt: 9 nedladdningar
Antalet nedladdningar är summan av nedladdningar för alla fulltexter. Det kan inkludera t.ex tidigare versioner som nu inte längre är tillgängliga.

doi
pubmed
urn-nbn

Altmetricpoäng

doi
pubmed
urn-nbn
Totalt: 19 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf