Academic Journal
Prognostic, predictive, and pharmacogenomic assessments of CDX2 refine stratification of colorectal cancer
| العنوان: | Prognostic, predictive, and pharmacogenomic assessments of CDX2 refine stratification of colorectal cancer |
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| المؤلفون: | Jarle Bruun, Anita Sveen, Rita Barros, Peter W. Eide, Ina Eilertsen, Matthias Kolberg, Teijo Pellinen, Leonor David, Aud Svindland, Olli Kallioniemi, Marianne G. Guren, Arild Nesbakken, Raquel Almeida, Ragnhild A. Lothe |
| المصدر: | Molecular Oncology, Vol 12, Iss 9, Pp 1639-1655 (2018) |
| بيانات النشر: | Wiley, 2018. |
| سنة النشر: | 2018 |
| المجموعة: | LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| مصطلحات موضوعية: | CDX2, colorectal cancer, drug sensitivity, pharmacogenomics, predictive biomarker, prognostic biomarker, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: | We aimed to refine the value of CDX2 as an independent prognostic and predictive biomarker in colorectal cancer (CRC) according to disease stage and chemotherapy sensitivity in preclinical models. CDX2 expression was evaluated in 1045 stage I–IV primary CRCs by gene expression (n = 403) or immunohistochemistry (n = 642) and in relation to 5‐year relapse‐free survival (RFS), overall survival (OS), and chemotherapy. Pharmacogenomic associations between CDX2 expression and 69 chemotherapeutics were assessed by drug screening of 35 CRC cell lines. CDX2 expression was lost in 11.6% of cases and showed independent poor prognostic value in multivariable models. For individual stages, CDX2 was prognostic only in stage IV, independent of chemotherapy. Among stage I–III patients not treated in an adjuvant setting, CDX2 loss was associated with a particularly poor survival in the BRAF‐mutated subgroup, but prognostic value was independent of microsatellite instability status and the consensus molecular subtypes. In stage III, the 5‐year RFS rate was higher among patients with loss of CDX2 who received adjuvant chemotherapy than among patients who did not. The CDX2‐negative cell lines were significantly more sensitive to chemotherapeutics than CDX2‐positive cells, and the multidrug resistance genes MDR1 and CFTR were significantly downregulated both in CDX2‐negative cells and in patient tumors. Loss of CDX2 in CRC is an adverse prognostic biomarker only in stage IV disease and appears to be associated with benefit from adjuvant chemotherapy in stage III. Early‐stage patients not qualifying for chemotherapy might be reconsidered for such treatment if their tumor has loss of CDX2 and mutated BRAF. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1878-0261 1574-7891 |
| Relation: | https://doaj.org/toc/1574-7891; https://doaj.org/toc/1878-0261 |
| DOI: | 10.1002/1878-0261.12347 |
| URL الوصول: | https://doaj.org/article/86ace7d506a24870a91ce2572c977013 |
| رقم الانضمام: | edsdoj.86ace7d506a24870a91ce2572c977013 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 18780261 15747891 |
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| DOI: | 10.1002/1878-0261.12347 |