Mohamed Ahmed Allam, Eble Michael J, Dahl Edgar, Jonigk Danny, Warkentin Svetlana
Department of Radiation Oncology, RWTH Aachen University, Aachen, Germany.
Center for Integrated Oncology Aachen, Bonn, Cologne and Duesseldorf (CIO ABCD), Aachen, Germany.
Clin Transl Radiat Oncol. 2024 Sep 3;49:100853. doi: 10.1016/j.ctro.2024.100853. eCollection 2024 Nov.
Hypoxia-inducible factor-1α (HIF-1α) is a crucial transcription factor activated under hypoxic conditions, known to regulate genes associated with tumor survival, progression, and response to therapy. This study aimed to evaluate the prognostic significance of HIF-1α expression in patients with anal squamous cell carcinoma (ASCC) undergoing chemoradiation therapy.
We conducted a retrospective analysis of 28 ASCC patients treated with intensity-modulated radiotherapy (IMRT) at our center from 2009 to 2022. HIF-1α expression was assessed via immunohistochemistry on formalin-fixed paraffin-embedded tissue specimens. Quantitative analysis of HIF-1α expression was performed, and its relationship with clinical outcomes, including disease-free survival (DFS), locoregional relapse-free survival (LRRFS), and overall survival (OS), was examined using Cox regression models. Furthermore, ASCC tissue specimens from 17 patients were analyzed for potential mutations using Sanger sequencing.
High HIF-1α expression was significantly associated with poorer DFS (p = 0.005), LRRFS (p = 0.012), and OS (p = 0.009). HIF1α expression was marginally significantly higher in males compared to females (p = 0.056) while there was no significant difference found based on tumor stage or p16 status. However, a positive correlation was identified between BMI and HIF-1α levels (Pearson correlation r = 0.5, p = 0.0084), suggesting a link between metabolic status and tumor hypoxia. Only one patient exhibited a PIK3CA mutation, preventing a reliable assessment of its correlation with HIF-1α expression.
Our findings underscore the importance of HIF-1α as a potential biomarker for predicting survival outcomes in ASCC patients treated with chemoradiation. The association between higher BMI and increased HIF-1α expression may provide insights into the interplay between metabolic health and tumor biology in ASCC. Further studies with larger cohorts are needed to validate these findings and explore targeted therapies focusing on HIF-1α modulation.
缺氧诱导因子-1α（HIF-1α）是一种在缺氧条件下被激活的关键转录因子，已知其可调节与肿瘤存活、进展及治疗反应相关的基因。本研究旨在评估HIF-1α表达在接受放化疗的肛管鳞状细胞癌（ASCC）患者中的预后意义。
我们对2009年至2022年在本中心接受调强放疗（IMRT）的28例ASCC患者进行了回顾性分析。通过对福尔马林固定石蜡包埋组织标本进行免疫组织化学评估HIF-1α表达。对HIF-1α表达进行定量分析，并使用Cox回归模型检查其与包括无病生存期（DFS）、局部区域无复发生存期（LRRFS）和总生存期（OS）在内的临床结局的关系。此外，使用桑格测序分析了17例患者的ASCC组织标本中的潜在突变。
高HIF-1α表达与较差的DFS（p = 0.005）、LRRFS（p = 0.012）和OS（p = 0.009）显著相关。男性的HIF1α表达略高于女性（p = 0.056），而基于肿瘤分期或p16状态未发现显著差异。然而，确定BMI与HIF-1α水平之间存在正相关（Pearson相关系数r = 0.5，p = 0.0084），表明代谢状态与肿瘤缺氧之间存在联系。仅1例患者出现PIK3CA突变，无法可靠评估其与HIF-1α表达的相关性。
我们的研究结果强调了HIF-1α作为预测接受放化疗的ASCC患者生存结局的潜在生物标志物的重要性。较高的BMI与增加的HIF-1α表达之间的关联可能为ASCC中代谢健康与肿瘤生物学之间的相互作用提供见解。需要更大队列的进一步研究来验证这些发现并探索针对HIF-1α调节的靶向治疗。
