Department of Endocrinology, Medical University of Sofia, Sofia, Bulgaria.
Molecular Medicine Center, Department of Medical Chemistry and Biochemistry, Medical University of Sofia, Sofia, Bulgaria.
Diagn Cytopathol. 2021 Sep;49(9):1045-1051. doi: 10.1002/dc.24816. Epub 2021 Jun 25.
Thyroid nodules are common ultrasound findings with malignancy rate 7%-15%. Our objective was to assess the relative expression of the tissue inhibitor of metalloproteinase-1 gene (TIMP1) and chitinase-3-like protein 1 gene (CHI3L1) in fine-needle aspiration biopsy (FNAB) washouts and the serum levels of their protein products (TIMP-1 and chitinase-3-like protein 1 known as YKL-40) in patients with papillary thyroid cancer (PTC) and patients with benign nodules. Furthermore, the correlation between gene expression and circulating protein product was evaluated.
Eighty patients who underwent FNAB in one tertiary center were recruited in the study. Forty with Bethesda V and VI nodules were operated and PTC was confirmed. The other 40 patients were with Bethesda II nodules. TIMP-1 and YKL-40 serum levels were measured in all subjects. The TIMP1 and CHI3L1 expression was assessed in FNAB washouts from 20 PTC patients and 20 benign cases using quantitative PCR.
The relative expression of TIMP1 and CHI3L1 was significantly higher in the PTC group than in the benign group (p < .001 for TIMP1; p = .018 for CHI3L1). The PTC patients had higher serum TIMP-1 than the patients with benign nodules (p = .036). We did not find significant difference in the YKL-40 level between the two groups. TIMP1 and CHI3L1 expression did not correlate with the serum levels of their protein products.
FNAB washouts could be used for identification of diagnostic markers. The increased TIMP1 and CHI3L1 expression implies a role of these genes in the PTC carcinogenesis.
甲状腺结节是常见的超声表现,其恶性率为 7%-15%。我们的目的是评估组织金属蛋白酶抑制剂-1 基因(TIMP1)和几丁质酶 3 样蛋白 1 基因(CHI3L1)在细针抽吸活检(FNAB)冲洗液中的相对表达,以及其蛋白产物(TIMP-1 和几丁质酶 3 样蛋白 1,即 YKL-40)在甲状腺乳头状癌(PTC)患者和良性结节患者中的血清水平。此外,还评估了基因表达与循环蛋白产物之间的相关性。
我们招募了在一家三级中心进行 FNAB 的 80 名患者参与这项研究。其中 40 名 Bethesda V 和 VI 结节患者进行了手术,证实为 PTC;其余 40 名患者为 Bethesda II 结节。所有患者均测量了 TIMP-1 和 YKL-40 的血清水平。使用定量 PCR 评估 20 名 PTC 患者和 20 名良性病例 FNAB 冲洗液中的 TIMP1 和 CHI3L1 表达。
与良性组相比,PTC 组 TIMP1 和 CHI3L1 的相对表达显著升高(TIMP1,p < 0.001;CHI3L1,p = 0.018)。PTC 患者的血清 TIMP-1 水平高于良性结节患者(p = 0.036)。我们没有发现两组之间 YKL-40 水平有显著差异。TIMP1 和 CHI3L1 表达与它们蛋白产物的血清水平没有相关性。
FNAB 冲洗液可用于鉴定诊断标志物。TIMP1 和 CHI3L1 的表达增加意味着这些基因在 PTC 发生过程中发挥作用。