Radiation-Enhanced AF1q Moves Center Stage as a Key Driver to Favorable Tumor Stage in Rectal Cancer Patients

IF 3.1 2区医学 Q2 ONCOLOGY Cancer Medicine Pub Date : 2025-03-10 DOI:10.1002/cam4.70658

Elisabeth S. Gruber, Georg Oberhuber, Elisabeth Gurnhofer, Robert Eferl, Gerald Timelthaler, Béla Teleky, D. I. Dietmar Georg, Joachim Widder, William Tse, Lukas Kenner

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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 (r_s = −0.468, p = 0.038) and IDO1 (r_s = −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.

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放射增强的AF1q作为直肠癌患者有利肿瘤分期的关键驱动因素移动中心阶段

体外（化疗）放疗后染色体1q （AF1Q）中all1融合基因的蛋白表达增强已被描述，但在胃肠道癌症中尚未得到充分研究。我们旨在研究AF1q在接受短期放射治疗的直肠癌（RC）患者中的表达，以及与RC预后关键标志物的可能相关性。方法选择75例计划手术的RC患者，局部中度晚期肿瘤（cT3Nx）患者术前接受高分割短期放射治疗（累积剂量25 Gy）。采用免疫组化分析评估AF1q、STAT1、IDO1等预后标志物（CD3/ CD8-Immunoscore、PD-L1）及标志物相关性。结果放疗肿瘤的AF1q表达量显著高于treatment-naïve样本(n = 60: AF1q+ vs 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)。具体而言，与treatment-naïve样本相比，放疗后的肿瘤显示高STAT1表达，但低IDO1表达（p = 0.019和p = 0.015）。总体而言，肿瘤AF1q表达增强与阴性淋巴结分期（p = 0.012）以及STAT1 （rs = - 0.468, p = 0.038）和IDO1表达降低（rs = - 0.246, p = 0.020）相关。结论AF1q在RC中表达，尤其是在短期放疗后。在这里，AF1q可能支持肿瘤抑制，可能通过参与促凋亡的STAT1轴。需要进一步的机制证据和涉及更大患者队列的研究来验证辐射诱导的、af1q驱动的肿瘤抑制作用，这可能会影响RC患者的预后。

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来源期刊

Cancer Medicine ONCOLOGY-

CiteScore

5.50

自引率

2.50%

发文量

907

审稿时长

19 weeks

期刊介绍： Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas: Clinical Cancer Research Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations Cancer Biology: Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery. Cancer Prevention: Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach. Bioinformatics: Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers. Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.