Prostate cancer survivors with symptoms of radiation cystitis have elevated fibrotic and vascular proteins in urine.
Prostate cancer survivors with symptoms of radiation cystitis have elevated fibrotic and vascular proteins in urine.
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DOI：
10.1371/journal.pone.0241388
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发表时间：
2020
期刊：
影响因子：
3.7
通讯作者：
Lamb LE
中科院分区：
文献类型：
--
作者：
Zwaans BMM;Nicolai HE;Chancellor MB;Lamb LE
盆腔癌的放射治疗可导致严重的膀胱损伤和放射性膀胱炎（RC），其特征在于慢性炎症、纤维化和血管损伤。由于膀胱活检很难获得，因此对RC的发展知之甚少。本研究的目的是利用有放射治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。从有（n = 85）和无（n = 9）放射治疗史的前列腺癌幸存者中采集94份尿样。15例有放射史的患者被正式诊断为放射性膀胱炎。使用Multiplex Luminex测量47种不同蛋白质的水平。在未辐照和辐照样品之间以及辐照样品内基于放射性膀胱炎诊断、症状评分或血尿进行比较。使用Welch t检验进行统计分析。在有放射治疗史的前列腺癌幸存者中，在接受放射性膀胱炎诊断的患者中检测到派1、TIMP 1、TIMP 2、HGF和VEGF-A水平升高。这些蛋白质在患有血尿或高症状评分的患者中也增加。除肉眼血尿和终末期放射性膀胱炎患者外，尿中未检测到炎性蛋白。活动性纤维化和血管窘迫可通过尿液中相关蛋白水平升高检测到。炎症仅在终末期放射性膀胱炎患者的尿液中检测到。这些结果表明，纤维化和血管损伤驱动放射性膀胱炎的发展，并可能导致更有针对性的治疗方法的发展。
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.