Department of Urology, William Beaumont Hospital, Royal Oak, Michigan, United States of America.
Oakland University William Beaumont School of Medicine, Rochester, Michigan, United States of America.
PLoS One. 2020 Oct 29;15(10):e0241388. doi: 10.1371/journal.pone.0241388. eCollection 2020.
Radiation for pelvic cancers can result in severe bladder damage and radiation cystitis (RC), which is characterized by chronic inflammation, fibrosis, and vascular damage. RC development is poorly understood because bladder biopsies are difficult to obtain. The goal of this study is to gain understanding of molecular changes that drive radiation-induced cystitis in cancer survivors using urine samples from prostate cancer survivors with history of radiation therapy. 94 urine samples were collected from prostate cancer survivors with (n = 85) and without (n = 9) history of radiation therapy. 15 patients with radiation history were officially diagnosed with radiation cystitis. Levels of 47 different proteins were measured using Multiplex Luminex. Comparisons were made between non-irradiated and irradiated samples, and within irradiated samples based on radiation cystitis diagnosis, symptom scores or hematuria. Statistical analysis was performed using Welch's t-test. In prostate cancer survivors with history of radiation therapy, elevated levels of PAI 1, TIMP1, TIMP2, HGF and VEGF-A were detected in patients that received a radiation cystitis diagnosis. These proteins were also increased in patients suffering from hematuria or high symptom scores. No inflammatory proteins were detected in the urine, except in patients with gross hematuria and end stage radiation cystitis. Active fibrosis and vascular distress is detectable in the urine through elevated levels of associated proteins. Inflammation is only detected in urine of patients with end-stage radiation cystitis disease. These results suggest that fibrosis and vascular damage drive the development of radiation cystitis and could lead to the development of more targeted treatments.
盆腔癌症的放射治疗可能导致严重的膀胱损伤和放射性膀胱炎（RC），其特征为慢性炎症、纤维化和血管损伤。RC 的发展机制尚未完全阐明，因为难以获取膀胱活检样本。本研究的目的是通过收集有放疗史的前列腺癌幸存者的尿液样本，了解导致癌症幸存者放射性膀胱炎的分子变化。共收集了 94 份来自有（n=85）和无（n=9）放疗史的前列腺癌幸存者的尿液样本。有放疗史的 15 名患者被正式诊断为放射性膀胱炎。使用 Multiplex Luminex 测定了 47 种不同蛋白质的水平。在非照射和照射样本之间以及根据放射性膀胱炎诊断、症状评分或血尿在照射样本内进行了比较。使用 Welch's t 检验进行了统计分析。在有放疗史的前列腺癌幸存者中，接受放射性膀胱炎诊断的患者尿液中检测到 PAI 1、TIMP1、TIMP2、HGF 和 VEGF-A 的水平升高。血尿或高症状评分的患者中这些蛋白也增加。尿液中未检测到炎症蛋白，除了有肉眼血尿和终末期放射性膀胱炎的患者。通过相关蛋白的水平升高，可以检测到活跃的纤维化和血管窘迫。仅在终末期放射性膀胱炎疾病的患者尿液中检测到炎症。这些结果表明纤维化和血管损伤是放射性膀胱炎发展的驱动因素，并可能导致更有针对性的治疗方法的发展。
