Phosphorylated FOXO1 Is a Novel Prognostic Factor for Patients with Pancreatic Cancer Receiving Multimodal Therapies.
Yu-Fen Jin, Miki Tomoeda, Shigenori Nagata, Katsuhiko Yoshizato, Masanori Kitamura, Michiko Yuki, Chiaki Kubo, Hidenori Yoshizawa, Hidenori Takahashi, Hiroaki Ohigashi, Osamu Ishikawa, Yasuhiko Tomita. Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan; Kobe International University, Hyogo, Japan
Background: Forkhead box O1 (FOXO1), a transcription factor, is a key regulator of cell cycle progression, and apoptosis, thus considered to be involved in cell transformation and tumorigenesis. Correlation of FOXO1 in tumor progression or prognosis has been reported in several human cancers, however, not in pancreatic ductal adenocarcinomas (PDAC).
Design: phosphorylated FOXO1 (p-FOXO1) expression in primary PDAC from 68 patients receiving neoadjuvant chemoradiotherapy, 43 male and 25 female, aged 41 to 81 (median 66) years, was evaluated by immunohistochemistry. Staining intensity of p-FOXO1 in the tumors was judged separately for the nucleus and cytoplasm and categorized as follows: level I, weaker than that of endothelial cells in the same specimen (including absent or faint staining); and level II, equal to or stronger than that of endothelial cells.
Results: Forty-three (63.2%) and 25 (36.8%) cases, and 54 (79.4%) and 14 (20.6%) cases showed p-FOXO level I and II expression in the nucleus and cytoplasm, respectively. Patinets with nuclear p-FOXO1 level I showed a significantly better overall survival rate than those with level II (P = 0.0003). No significant difference was observed in the cytoplasmic p-FOXO1 classification, however correlation between cytoplasmic p-FOXO1 expression and histological assessment of chemoradiation effect grade (I /IIa versus IIb/III) was observed (P = 0.01).
|Cytoplasmic p-FOXO1 expression||p value|
|Level I (n=54)||Level II (n=14)|
|Histological Assessment of||IIa||18||64.3%||10||35.7%|