Supplementary Material for: Early Loss of Forkhead Transcription Factor, O Subgroup, Member 1 Protein in the Development of Pancreatic Ductal Adenocarcinoma Al-Zoughbi W. Schauer S. Pichler M. Hoefler G. 10.6084/m9.figshare.7098002.v1 https://karger.figshare.com/articles/dataset/Supplementary_Material_for_Early_Loss_of_Forkhead_Transcription_Factor_O_Subgroup_Member_1_Protein_in_the_Development_of_Pancreatic_Ductal_Adenocarcinoma/7098002 <b><i>Objectives:</i></b> Forkhead transcription factor, O subgroup, member 1 (FOXO1) is a regulatory protein that plays an essential role in cellular homeostasis. A biological function as a tumor suppressor has been proposed. Here, we examined FOXO1 expression in human pancreatic ductal adenocarcinoma (PDAC) and its precursor lesions. <b><i>Methods:</i></b> We immunohistochemically labeled tissue samples from 47 patients with PDAC for FOXO1 protein. In addition, we extracted data from the Cancer Genome Atlas and the Cancer Cell Line Encyclopedia and studied a potential association with well-established genetic variants. A publicly available microarray dataset of 102 PDAC samples was used to explore the influence of <i>FOXO1</i> expression on patients’ clinical outcome. <b><i>Results:</i></b> Normal ductal epithelium universally expressed nuclear and cytoplasmic FOXO1. Reduced expression was observed in PanIN lesions and PDAC of all cases. Analysis of several datasets showed that the <i>FOXO1</i> gene transcript levels do not correlate with <i>KRAS</i>, <i>TP53</i>, <i>SMAD4</i>, or <i>CDKN2A</i> mutation status, but positively correlate with patients’ outcomes. <b><i>Conclusions:</i></b> Loss of FOXO1 protein is identified as an early event during PDAC development and may be independent of the top 4 mutated cancer genes. Because of its strong expression in normal ductal cells, immunohistochemical detection of FOXO1 can function as a valuable test to establish the diagnosis of transformation and malignancy in pancreatic tissues. 2018-09-18 11:43:16 Pancreas Pancreatic intraepithelial neoplasia Forkhead transcription factor, O subgroup, member 1 Immunohistochemistry KRAS Tumor suppressor