Distinct gene expression profiles of proximal and distal colorectal cancer: implications for cytotoxic and targeted therapy
| Autor: | Martin K. H. Maus, Afsaneh Barzi, Stephanie H. Astrow, Gary Zeger, Diana L. Hanna, Fotios Loupakis, Jack Hsiang, Heinz-Josef Lenz, Takeru Wakatsuki, Craig Stephens, Peter P. Grimminger, Dongyun Yang |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Colorectal cancer Angiogenesis medicine.medical_treatment medicine.disease_cause Thymidylate synthase Targeted therapy predictive biomarkers Drug Delivery Systems 0302 clinical medicine Prospective Studies Epidermal growth factor receptor Aged 80 and over 0303 health sciences Middle Aged Prognosis Primary tumor 3. Good health DNA-Binding Proteins ErbB Receptors 030220 oncology & carcinogenesis Colonic Neoplasms Molecular Medicine Female KRAS Colorectal Neoplasms Adult Proto-Oncogene Proteins B-raf colorectal cancer Antineoplastic Agents Biology Article BRAF Proto-Oncogene Proteins p21(ras) 03 medical and health sciences Biomarkers Tumor Genetics medicine Humans RNA Messenger neoplasms tumor location Aged 030304 developmental biology Pharmacology Rectal Neoplasms Gene Expression Profiling Endonucleases medicine.disease Vascular Endothelial Growth Factor Receptor-2 digestive system diseases biology.protein Cancer research ERCC1 |
| Zdroj: | The pharmacogenomics journal |
| ISSN: | 1473-1150 1470-269X |
| DOI: | 10.1038/tpj.2014.73 |
| Popis: | Colorectal cancer (CRC) is a heterogeneous disease with genetic profiles and clinical outcomes dependent on the anatomic location of the primary tumor. How location has an impact on the molecular makeup of a tumor and how prognostic and predictive biomarkers differ between proximal versus distal colon cancers is not well established. We investigated the associations between tumor location, KRAS and BRAF mutation status, and the messenger RNA (mRNA) expression of proteins involved in major signaling pathways, including tumor growth (epidermal growth factor receptor (EGFR)), angiogenesis (vascular endothelial growth factor receptor 2 (VEGFR2)), DNA repair (excision repair cross complement group 1 (ERCC1)) and fluoropyrimidine metabolism (thymidylate synthase (TS)). Formalin-fixed paraffin-embedded tumor specimens from 431 advanced CRC patients were analyzed. The presence of seven different KRAS base substitutions and the BRAF V600E mutation was determined. ERCC1, TS, EGFR and VEGFR2 mRNA expression levels were detected by reverse transcriptase-PCR. BRAF mutations were significantly more common in the proximal colon (P |
| Databáze: | OpenAIRE |
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