Department of Microbiology and Immunology, New York Medical College, Valhalla, NY, USA.
Genetics and Molecular Biology Research Group, University of Cartagena, Cartagena, Colombia.
Cancer Biomark. 2019;24(1):71-83. doi: 10.3233/CBM-181758.
Thyroid cancer is the most common endocrine malignancy worldwide, with the predominant form papillary thyroid carcinoma (PTC) representing approximately 80% of cases.
This study was addressed to identify potential genes and pathways involved in the pathogenesis of PTC and potential novel biomarkers for this disease.
Gene expression profiling was carried out by DNA microarray technology. Validation of microarray data by qRT-PCR, western blot, and enzyme linked immunosorbent assay was also performed in a selected set of genes and gene products, with the potential to be used as diagnostic or prognostic biomarkers, such as those associated with cell adhesion, extracellular matrix (ECM) remodeling and immune/inflammatory response.
In this study we found that upregulation of extracellular activities, such as proteoglycans, ECM-receptor interaction, and cell adhesion molecules, were the most prominent feature of PTC. Significantly over-expressed genes included SDC1 (syndecan 1), SDC4 (syndecan 4), KLK7 (kallikrein-related peptidase 7), KLK10 (kallikrein-related peptidase 10), SLPI (secretory leukocyte peptidase inhibitor), GDF15 (growth/differentiation factor-15), ALOX5 (arachidonate 5-lipoxygenase), SFRP2 (secreted Frizzled-related protein 2), among others. Further, elevated KLK10 levels were detected in patients with PTC. Many of these genes belong to KEGG pathway "Proteoglycans in cancer".
Using DNA microarray analysis allowed the identification of genes and pathways with known important roles in malignant transformation, and also the discovery of novel genes that may be potential biomarkers for PTC.
甲状腺癌是全球最常见的内分泌恶性肿瘤，其中以占比约 80%的甲状腺乳头状癌（PTC）最为常见。
本研究旨在确定参与 PTC 发病机制的潜在基因和通路，以及该疾病的潜在新型生物标志物。
采用 DNA 微阵列技术进行基因表达谱分析。通过 qRT-PCR、western blot 和酶联免疫吸附试验对选定的一组基因和基因产物进行了微阵列数据的验证，这些基因和基因产物具有作为诊断或预后生物标志物的潜力，例如与细胞黏附、细胞外基质（ECM）重塑和免疫/炎症反应相关的标志物。
在本研究中，我们发现细胞外活动（如蛋白聚糖、ECM 受体相互作用和细胞黏附分子）的上调是 PTC 最显著的特征。显著过表达的基因包括 SDC1（黏附素 1）、SDC4（黏附素 4）、KLK7（激肽释放酶相关肽酶 7）、KLK10（激肽释放酶相关肽酶 10）、SLPI（分泌白细胞蛋白酶抑制剂）、GDF15（生长/分化因子-15）、ALOX5（花生四烯酸 5-脂氧合酶）、SFRP2（分泌卷曲相关蛋白 2）等。此外，在 PTC 患者中检测到 KLK10 水平升高。其中许多基因属于 KEGG 通路“癌症中的蛋白聚糖”。
使用 DNA 微阵列分析可以鉴定出已知在恶性转化中具有重要作用的基因和通路，并发现可能是 PTC 潜在生物标志物的新基因。
