Department of Urology, Medical School, University of Pecs, Pecs, Hungary.
Department of Urology, Medical School, University of Debrecen, Debrecen, Hungary.
Anticancer Res. 2020 Nov;40(11):6525-6530. doi: 10.21873/anticanres.14676.
BACKGROUND/AIM: End-stage kidney disease is characterized by chronic inflammation and frequent development of cancer. The level of circulating vitamin D is generally low in patients with end-stage renal disease (ESRD). Experimental studies have implicated the role of dysfunctional vitamin D metabolism in tumorigenesis.
We analyzed the expression of vitamin D receptor (VDR), cytochrome P450 family 27 subfamily B member 1 (CYP27B1) and cytochrome P450 family 24 subfamily A member 1 (CYP24A1), the key genes involved in vitamin D signaling, in kidneys from patients with ESRD, tissue microarrays containing ESRD-associated renal cell tumors, as well as in their precursor lesions by immunohistochemistry.
Kidneys from patients with ESRD showed strong structural rearrangement with only few tubules and epithelial cell groups embedded in fibrotic-inflammatory stroma. Only an estimated 1-3% of the epithelial cells showed positive staining with antibodies to VDR, CYP27B1 and CYP24A1, which contrasted with the 100%, 40-50% and 40-50% of positively stained cells, respectively, found in normal kidneys. Down-regulation of the vitamin D signaling proteins was found in patients with renal cancer, with the exception of tumors and their precursors occurring exclusively in ESRD.
The significantly reduced activity of CYP27B1 in kidney from patients with ESRD explains the low level of circulating vitamin D. We suggest that the lack of anti-tumorigenic effect of vitamin D is a crucial factor in the frequent development of unique types of renal cell cancer in in patients with ESRD.
背景/目的：终末期肾病的特征是慢性炎症和癌症的频繁发生。终末期肾病（ESRD）患者的循环维生素 D 水平通常较低。实验研究表明，维生素 D 代谢功能障碍在肿瘤发生中起作用。
我们通过免疫组织化学分析了 ESRD 患者肾脏、包含 ESRD 相关肾细胞肿瘤的组织微阵列以及其前体病变中维生素 D 信号转导的关键基因维生素 D 受体（VDR）、细胞色素 P450 家族 27 亚家族 B 成员 1（CYP27B1）和细胞色素 P450 家族 24 亚家族 A 成员 1（CYP24A1）的表达。
ESRD 患者的肾脏表现出强烈的结构重排，只有少数肾小管和上皮细胞群嵌入纤维炎性基质中。只有约 1-3%的上皮细胞对 VDR、CYP27B1 和 CYP24A1 的抗体呈阳性染色，而在正常肾脏中，这三种抗体分别有 100%、40-50%和 40-50%的细胞呈阳性染色。在患有肾癌的患者中发现了维生素 D 信号蛋白的下调，除了仅发生在 ESRD 中的肿瘤及其前体。
ESRD 患者肾脏中 CYP27B1 的活性显著降低，解释了循环维生素 D 水平较低的原因。我们认为，维生素 D 缺乏抗肿瘤作用是 ESRD 患者频繁发生独特类型肾细胞癌的关键因素。
