Distinct gene expression profiles of proximal and distal colorectal cancer: implications for cytotoxic and targeted therapy.

摘要: Colorectal cancer (CRC) is a heterogeneous disease with genetic profiles and clinical outcomes dependent on the anatomic location of primary tumor. How has an impact molecular makeup tumor how prognostic predictive biomarkers differ between proximal versus distal colon cancers not well established. We investigated associations location, KRAS BRAF mutation status, messenger RNA (mRNA) expression proteins involved in major signaling pathways, including growth (epidermal factor receptor (EGFR)), angiogenesis (vascular endothelial 2 (VEGFR2)), DNA repair (excision cross complement group 1 (ERCC1)) fluoropyrimidine metabolism (thymidylate synthase (TS)). Formalin-fixed paraffin-embedded specimens from 431 advanced CRC patients were analyzed. The presence seven different base substitutions V600E was determined. ERCC1, TS, EGFR VEGFR2 mRNA levels detected by reverse transcriptase-PCR. mutations significantly more common (P<0.001), whereas occurred at similar frequencies throughout colorectum. Rectal had higher ERCC1 compared tumors (P=0.001), increased TS (P=0.02). Mutant status associated lower gene multivariate analysis. In subgroup analysis, this association remained significant for all genes rectal cancers. patterns biomarkers, as depend location. Prospective studies are warranted to confirm these findings determine underlying mechanisms.