Loss of CDX2 and high COX2 ( PTGS2 ) expression in metastatic colorectal cancer

Lack of expression of the tumour suppressor gene caudal-type homeobox 2 ( ) associates with poor outcomes in early stage colorectal cancer (CRC). Yet its prognostic value in the context of other prognostic biomarkers in metastatic CRC (mCRC) is unknown. Overexpressed cyclooxygenase-2 (COX2) has been...

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Published inEcancermedicalscience Vol. 18; p. 1666
Main Authors Caldas, Álvaro M C, Nunes, Warley A, Taboada, Rodrigo, Cesca, Marcelle G, Germano, Janaína N, Riechelmann, Rachel P
Format Journal Article
LanguageEnglish
Published England Cancer Intelligence 2024
Subjects
Biomarkers
Cancer therapies
Cell growth
Chemotherapy
Colorectal cancer
Epidermal growth factor
Genes
Inflammation
Kinases
Medical prognosis
Metastasis
Mutation
Patients
Protein expression
Proteins
Tumors
Brazil
COX2
metastatic colorectal cancer
BRAF
CDX2
chemotherapy
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Summary:Lack of expression of the tumour suppressor gene caudal-type homeobox 2 ( ) associates with poor outcomes in early stage colorectal cancer (CRC). Yet its prognostic value in the context of other prognostic biomarkers in metastatic CRC (mCRC) is unknown. Overexpressed cyclooxygenase-2 (COX2) has been reported in advanced CRC. However, CDX2 and COX2 relationship in mCRC remains undetermined. We aimed to assess their expression in mCRC tumours from a clinically characterised cohort and their influence on overall survival (OS) and progression-free survival (PFS) in first line. Among 720 consecutive mCRC patients, 346 had tumour samples appropriate for tissue microarray assembly and immunohistochemistry analyses. Clinical and survival data were retrospectively assessed. Loss of expression was detected in 27 (7.8%) samples, enriched in poorly differentiated tumours (20%; < 0.01) and in those with the p.V600E variant (40%; < 0.01). Most tumours (93.4%) expressed COX2. COX2-negative samples were enriched in poorly differentiated mCRC. In unadjusted analyses, median OS ( < 0.001) and median PFS ( < 0.05) were inferior for patients with CDX2-negative versus CDX2-positive tumours. In conclusion, loss of was significantly associated with poorly differentiated mCRC and p. allele and a prognostic marker of worse OS.
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ISSN:1754-6605
1754-6605
DOI:10.3332/ecancer.2024.1666