Elisabeth S. Gruber Elisabeth S. Gruber Georg Oberhuber Georg Oberhuber Elisabeth Gurnhofer Elisabeth Gurnhofer Robert Eferl Robert Eferl Gerald Timelthaler Gerald Timelthaler Béla Teleky Béla Teleky D. I. Dietmar Georg D. I. Dietmar Georg Joachim Widder Joachim Widder William Tse William Tse Lukas Kenner Lukas Kenner Wiley 2025 Enhanced protein expression of ALL1-fused gene from chromosome 1q (AF1Q) after (chemo)radiotherapy has been described in vitro, but is largely understudied in gastrointestinal cancer. We aimed to investigate AF1q expression in rectal cancer (RC) patients treated with short-term radiation therapy and a possible correlation with markers crucial for RC prognosis. A cohort of 75 RC patients scheduled for surgery was defined and patients with moderately locally advanced tumors (cT3Nx) received preoperative hyperfractionated short-term radiation therapy (cumulative dose 25 Gy). Immunohistochemical analysis was conducted to assess AF1q, STAT1, IDO1 and other prognostic markers (CD3/CD8—Immunoscore, PD-L1) and marker correlations were evaluated. Irradiated tumors exhibited significantly higher AF1q expression than treatment-naïve samples (n = 60: AF1q + to AF1q+++ 98.3% (n = 59), AF1q- 1.7% (n = 1) vs. n = 15: AF1q + 78.6% (n = 11), AF1q- 21.4% (n = 4); p < 0.001). Specifically, irradiated tumors showed high STAT1, but low IDO1 expression compared to treatment-naïve samples (p = 0.019 and p = 0.015, respectively). Overall, enhanced tumoral AF1q expression was associated with negative lymph node stage (p = 0.012) as well as with diminished expression of STAT1 (rs = −0.468, p = 0.038) and IDO1 (rs = −0.246, p = 0.020). AF1q is expressed in RC, especially after short-term radiation therapy. Here, AF1q may support tumor suppression, possibly through the involvement of the pro-apoptotic STAT1 axis. Further mechanistic evidence and investigation involving a larger patient cohort are needed to validate a radiation-induced, AF1q-driven tumor-suppressing effect, which may impact RC patient outcomes. PDFDocument eng 2025-04-07T08:41:04.263777Z 2025 Humans Rectal Neoplasms Pathology Rectal Neoplasms Radiotherapy Rectal Neoplasms Metabolism Rectal Neoplasms Genetics Male Female Middle Aged Aged Neoplasm Staging STAT1 Transcription Factor Metabolism STAT1 Transcription Factor Genetics Prognosis Biomarkers, Tumor Metabolism Indoleamine-Pyrrole 2,3,-Dioxygenase Metabolism Indoleamine-Pyrrole 2,3,-Dioxygenase Genetics Adult Aged, 80 and over B7-H1 Antigen Metabolism B7-H1 Antigen Genetics 1021779 b application/pdf http://creativecommons.org/licenses/by/4.0/