Mayer Philipp, Kraft Anne, Witzel Hagen R, Marnet Nicole, Hörner Nina, Roth Wilfried, Heinrich Stefan, Hackert Thilo, Bergmann Frank, Kauczor Hans-Ulrich, Klauss Miriam, Gaida Matthias M
Clinic for Diagnostic and Interventional Radiology, University Hospital Heidelberg, 69120 Heidelberg, Germany.
Institute of Pathology, University Medical Center Mainz, JGU-Mainz, 55131 Mainz, Germany.
Cancers (Basel). 2020 Dec 30;13(1):89. doi: 10.3390/cancers13010089.
Hypoxia is a hallmark of pancreatic cancer (PDAC) due to its compact and extensive fibrotic tumor stroma. Hypoxia contributes to high lethality of this disease, by inducing a more malignant phenotype and resistance to radiation and chemotherapy. Thus, non-invasive methods to quantify hypoxia could be helpful for treatment decisions, for monitoring, especially in non-resectable tumors, or to optimize personalized therapy. In the present study, we investigated whether tumor hypoxia in PDAC is reflected by diffusion-weighted magnetic resonance imaging (DW-MRI), a functional imaging technique, frequently used in clinical practice for identification and characterization of pancreatic lesions. DW-MRI assesses the tissue microarchitecture by measuring the diffusion of water molecules, which is more restricted in highly compact tissues. As reliable surrogate markers for hypoxia, we determined Blimp-1 (B-lymphocyte induced maturation protein), a transcription factor, as well as vascular endothelial growth factor (VEGF), which are up-regulated in response to hypoxia. In 42 PDAC patients, we observed a close association between restricted water diffusion in DW-MRI and tumor hypoxia in matched samples, as expressed by high levels of Blimp-1 and VEGF in tissue samples of the respective patients. In summary, our data show that DW-MRI is well suited for the evaluation of tumor hypoxia in PDAC and could potentially be used for the identification of lesions with a high hypoxic fraction, which are at high risk for failure of radiochemotherapy.
由于胰腺癌（PDAC）致密且广泛的纤维化肿瘤基质，缺氧是其一个标志。缺氧通过诱导更恶性的表型以及对放疗和化疗产生抗性，导致了这种疾病的高致死率。因此，量化缺氧的非侵入性方法可能有助于治疗决策、监测，尤其是对于不可切除的肿瘤，或者优化个性化治疗。在本研究中，我们调查了扩散加权磁共振成像（DW-MRI）这一在临床实践中常用于识别和表征胰腺病变的功能成像技术，是否能反映PDAC中的肿瘤缺氧情况。DW-MRI通过测量水分子的扩散来评估组织微结构，在高度致密的组织中水分子扩散受到更多限制。作为缺氧的可靠替代标志物，我们测定了转录因子Blimp-1（B淋巴细胞诱导成熟蛋白）以及血管内皮生长因子（VEGF），它们在缺氧时会上调。在42例PDAC患者中，我们观察到DW-MRI中受限的水扩散与匹配样本中的肿瘤缺氧之间存在密切关联，这表现为相应患者组织样本中高水平的Blimp-1和VEGF。总之，我们的数据表明DW-MRI非常适合评估PDAC中的肿瘤缺氧情况，并且有可能用于识别缺氧分数高的病变，这些病变对放化疗失败的风险很高。
