Balla B, Tobiás B, Kósa J P, Podani J, Horváth P, Nagy Z, Horányi J, Járay B, Székely E, Krenács L, Árvai K, Dank M, Putz Z, Szabó B, Szili B, Valkusz Z, Vasas B, Győri G, Lakatos P, Takács I
1st Department of Internal Medicine, Semmelweis University, Korányi S. u. 2/a, Budapest, 1083, Hungary.
Biological Institute, Eötvös Loránd University, Pázmány Péter stny. 1/c, Budapest, 1117, Hungary.
J Endocrinol Invest. 2015 Mar;38(3):313-21. doi: 10.1007/s40618-014-0165-7. Epub 2014 Sep 9.
The aims of the present study were to examine gene and protein expression of the vitamin D-inactivating 24-hyroxylase (CYP24A1) and the activating 1-alpha-hydroxylase (CYP27B1) enzyme in human papillary thyroid cancer (PTC), furthermore, to investigate the association between CYP24A1 expression and numerous clinical, histological parameters and somatic oncogene mutation status of thyroid tumor tissues.
Gene expression analysis was carried out in 100 Hungarian thyroid samples, both normal and papillary tumor tissue sections of the same patient. The specific mRNA to the selected genes was analyzed by TaqMan probe-based quantitative real-time RT-PCR. The somatic oncogene mutation states of BRAF, NRAS, HRAS and KRAS were also tested.
CYP24A1 mRNA expression was markedly increased in 52 cases (52%) of the examined papillary cancers compared with that of normal thyroid tissue. There was a tendency toward difference in the distribution of high-level CYP24A1 in the PTC accompanied with somatic oncogene mutation. Positive correlation was seen between increased CYP24A1 expression rate and a group of variables reflecting tumor malignity (mainly vascular invasion, lymph node metastasis, tumor size, hypothyreosis) by principal components analysis. No significant alteration was seen in CYP27B1 gene expression between neoplastic and normal tissues.
A definite alteration was seen in vitamin D3-inactivating CYP24A1 gene activity in PTC compared to their normal tissues on a relatively large patient population. Our findings raise the possibility that CYP24A1 may also directly be involved in thyroid carcinogenesis.
本研究旨在检测人甲状腺乳头状癌（PTC）中维生素D失活酶24-羟化酶（CYP24A1）和激活酶1-α-羟化酶（CYP27B1）的基因和蛋白表达，此外，研究CYP24A1表达与甲状腺肿瘤组织的众多临床、组织学参数及体细胞癌基因突变状态之间的关联。
对100例匈牙利甲状腺样本进行基因表达分析，这些样本包括同一患者的正常和乳头状肿瘤组织切片。通过基于TaqMan探针的定量实时逆转录聚合酶链反应（RT-PCR）分析所选基因的特异性mRNA。同时检测BRAF、NRAS、HRAS和KRAS的体细胞癌基因突变状态。
与正常甲状腺组织相比，在52例（52%）检测的乳头状癌中CYP24A1 mRNA表达显著增加。伴有体细胞癌基因突变的PTC中，高水平CYP24A1的分布存在差异趋势。通过主成分分析发现，CYP24A1表达率增加与一组反映肿瘤恶性程度的变量（主要是血管侵犯、淋巴结转移、肿瘤大小、甲状腺功能减退）呈正相关。肿瘤组织和正常组织之间CYP27B1基因表达未见明显改变。
在相对较大的患者群体中，与正常组织相比，PTC中维生素D3失活的CYP24A1基因活性有明显改变。我们的研究结果提示CYP24A1可能也直接参与甲状腺癌的发生。
