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• W4361943485 abstract "<div>Abstract<p><b>Purpose:</b> Prognostic studies on transcription factors acting at specific promoter elements have never been done so far. However, in tumors with long necessary follow-up, such as colorectal cancer, early-risk predictors would be needed. The invasion-related gene <i>u-PAR</i> is regulated via an activator protein 2 (AP-2)/Sp1 (−152/−135) and an AP-1 binding promoter motif (−190/−171), mediating <i>u-PAR</i> induction by K-Ras and Src. The present study was done to give first evidence for early prognostic relevance of transcription factors differentially bound to the <i>u-PAR</i> promoter, and their molecular inducers, in colorectal cancer.</p><p><b>Experimental Design:</b> Tumor/normal tissues of 92 prospectively followed (median = 26.3 months) patients were analyzed for Src activity/protein, <i>K-ras</i> mutations, and transcription factor binding to both <i>u-PAR</i> promoter motifs (<i>in vivo</i> gel shift, kinase assay, and PCR).</p><p><b>Results:</b> Kaplan-Meier/Mantel-Cox analysis showed a significant correlation among elevated Sp1/Sp3 binding to region −152/−135 (<i>P</i> = 0.002 and <i>P</i> = 0.006), the combinations of Sp1/AP-2 and Sp1/AP-1 binding to both motifs (<i>P</i> = 0.010 and <i>P</i> = 0.005), and Sp1 binding/high Src protein in tumors (<i>P</i> < 0.001), with poor survival. Survival decreased with the number of bound transcription factors to both motifs, with binding of three factors defining a high-risk group (<i>P</i> = 0.021). In multivariate analysis, elevated Sp1 binding, combinations of Sp1/AP-2 binding and Sp1/AP-1 binding, or Sp1 binding/high Src were independent prognostic variables; u-PAR expression itself being not yet prognostic. A first molecular staging model (CART) was defined, providing novel early high-risk groups (mean survival time as low as for non-curatively resected patients) from these variables.</p><p><b>Conclusions:</b> This study defines transcription factors acting at specific promoter elements of an invasion-related gene, mediating specific signaling, as novel, independent, early predictors of prognosis in colorectal cancer.</p></div>" @default.
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• W4361943485 date "2023-03-31" @default.
• W4361943485 modified "2023-10-14" @default.
• W4361943485 title "Data from Analysis of Specific Transcriptional Regulators as Early Predictors of Independent Prognostic Relevance in Resected Colorectal Cancer" @default.
• W4361943485 doi "https://doi.org/10.1158/1078-0432.c.6518377" @default.
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