Radiation‐Enhanced AF1q Moves Center Stage as a Key Driver to Favorable Tumor Stage in Rectal Cancer Patients
ABSTRACT Background 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 r...
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| Format: | Article |
| Language: | English |
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Wiley
2025-03-01
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| Series: | Cancer Medicine |
| Online Access: | https://doi.org/10.1002/cam4.70658 |
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| author | Elisabeth S. Gruber Georg Oberhuber Elisabeth Gurnhofer Robert Eferl Gerald Timelthaler Béla Teleky D. I. Dietmar Georg Joachim Widder William Tse Lukas Kenner |
| author_facet | Elisabeth S. Gruber Georg Oberhuber Elisabeth Gurnhofer Robert Eferl Gerald Timelthaler Béla Teleky D. I. Dietmar Georg Joachim Widder William Tse Lukas Kenner |
| author_sort | Elisabeth S. Gruber |
| collection | DOAJ |
| description | ABSTRACT Background 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. Methods 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. Results 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). Conclusion 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. |
| format | Article |
| id | doaj-art-dcb10b802ba34d61bfa1fb37e969a92d |
| institution | DOAJ |
| issn | 2045-7634 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj-art-dcb10b802ba34d61bfa1fb37e969a92d2025-08-20T02:59:07ZengWileyCancer Medicine2045-76342025-03-01145n/an/a10.1002/cam4.70658Radiation‐Enhanced AF1q Moves Center Stage as a Key Driver to Favorable Tumor Stage in Rectal Cancer PatientsElisabeth S. Gruber0Georg Oberhuber1Elisabeth Gurnhofer2Robert Eferl3Gerald Timelthaler4Béla Teleky5D. I. Dietmar Georg6Joachim Widder7William Tse8Lukas Kenner9Division of Visceral Surgery, Department of General Surgery Medical University Vienna Vienna AustriaDepartment of Experimental and Animal Pathology Clinical Institute of Pathology, Medical University Vienna Vienna AustriaDepartment of Experimental and Animal Pathology Clinical Institute of Pathology, Medical University Vienna Vienna AustriaCenter for Cancer Research Medical University Vienna Vienna AustriaCenter for Cancer Research Medical University Vienna Vienna AustriaCenter for Biomedical Research and Translational Surgery Medical University Vienna Vienna AustriaDepartment of Radiation Oncology Medical University of Vienna Vienna AustriaComprehensive Cancer Center Medical University Vienna Vienna AustriaDepartment of Medicine, School of Medicine Case Western Reserve University Cleveland Ohio USADepartment of Experimental and Animal Pathology Clinical Institute of Pathology, Medical University Vienna Vienna AustriaABSTRACT Background 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. Methods 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. Results 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). Conclusion 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.https://doi.org/10.1002/cam4.70658 |
| spellingShingle | Elisabeth S. Gruber Georg Oberhuber Elisabeth Gurnhofer Robert Eferl Gerald Timelthaler Béla Teleky D. I. Dietmar Georg Joachim Widder William Tse Lukas Kenner Radiation‐Enhanced AF1q Moves Center Stage as a Key Driver to Favorable Tumor Stage in Rectal Cancer Patients Cancer Medicine |
| title | Radiation‐Enhanced AF1q Moves Center Stage as a Key Driver to Favorable Tumor Stage in Rectal Cancer Patients |
| title_full | Radiation‐Enhanced AF1q Moves Center Stage as a Key Driver to Favorable Tumor Stage in Rectal Cancer Patients |
| title_fullStr | Radiation‐Enhanced AF1q Moves Center Stage as a Key Driver to Favorable Tumor Stage in Rectal Cancer Patients |
| title_full_unstemmed | Radiation‐Enhanced AF1q Moves Center Stage as a Key Driver to Favorable Tumor Stage in Rectal Cancer Patients |
| title_short | Radiation‐Enhanced AF1q Moves Center Stage as a Key Driver to Favorable Tumor Stage in Rectal Cancer Patients |
| title_sort | radiation enhanced af1q moves center stage as a key driver to favorable tumor stage in rectal cancer patients |
| url | https://doi.org/10.1002/cam4.70658 |
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