Figure 10.

Association of AP4 with metastasis and poor patient survival. (A) The intensity of nuclear AP4 staining was assigned the following scores: none = −, weak = +, moderate = ++, and strong = +++ expression. Examples of representative immunohistochemistry results are shown. Bars, 100 µm. (B) AP4 expression in primary colon cancer samples of 110 patients who underwent surgical tumor resection at the Ludwig-Maximilians University of Munich between 1994 and 2005. Percentage values are given in parentheses. 55 control cases had colon cancers without distant metastases at the time of diagnosis and disease-free survival of at least 5 yr after primary surgical resection. Data were analyzed using the χ² test. (C) Kaplan–Meier plot of CRC specimens (n = 227) with weak (1+), moderate (2+), and strong (3+) AP4 expression. A log-rank test indicated statistical significance (P = 0.016). (D) The expression of AP4 and c-MYC mRNA was analyzed in the TCGA CRC dataset (http://cancergenome.nih.gov/). 197 of 276 CRC samples were informative. The linear regression was determined using a Pearson correlation analyses. Dashed lines indicate the confidence interval. (E) Model summarizing the main findings of this study. c-MYC induces expression of AP4, which either induces or represses target genes, of which selected examples are depicted. The biological outcomes of the AP4-mediated regulations with relevance to cancer are indicated in gray boxes. Dotted lines indicate inferred biological functions of AP4 that remain to be proven experimentally. The gene or genes linking AP4 to the regulation of stemness remain to be characterized.