Department of Pathology, Anhui Medical University, Hefei, Anhui, China.
Department of Pathology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.
PLoS One. 2018 Jul 13;13(7):e0200290. doi: 10.1371/journal.pone.0200290. eCollection 2018.
Papillary thyroid carcinoma (PTC) is the most common endocrine cancer with a significantly increase of the incidence recently. Several cytokines, such as thyroid peroxidase (TPO), cluster of differentiation 56 (CD56), Galectin-3, mesothelial cell (MC), cytokeratin 19 (CK19) and BRAF (B-raf) were recommended to be tested by immunohistochemistry (IHC) for a definitive diagnosis, but were still limited in clinical use because of their relative lower sensitivity and specificity. MicroRNA (miRNA), as a new molecular biomarkers, however, has not been reported yet so far. To address this, hsa-miR-200a-5p, a miRNA, was selected and detected in PTC patients by in situ hybrization with benign thyroid tumor with papillary hyperplasia as a control, and the differential expression of hsa-miR-200a-5p between fresh PTC tissues and control was detected by qRT-PCR. Expressive levels of cytokines of TPO, CD56, Galectin-3, MC, CK19 and B-raf were also detected by immunohistochemistry. The correlation was analyzed by SPSS software using Spearman methods. As expected, the hsa-miR-200a-5p expressive level was significantly increased in PTC patients, compared to that of control, and was consistent with that of TPO, CD56, Galectin-3, MC, CK19 and B-raf. In addition, expression of hsa-miR-200a-5p showed negative correlation to that of TPO (rs = - 0.734; **: P < 0.01) and CD56 (rs = - 0.570; **: P < 0.01), but positive correlation to that of Galectin-3 (rs = 0.601; **: P < 0.01), MC (rs = 0.508; **: P < 0.01), CK19 (rs = 0.712; **: P < 0.01) and B-raf (rs = 0.378; **: P < 0.01). PTC and papillary benign thyroid papillary hyperplasia are difficult to distinguish in morphology, so requiring immunohistochemistry to further differentiate the diagnosis, however, for the existing clinical common diagnostic marker for immunohistochemistry, the sensitivity and accuracy are low, it is easy to miss diagnosis. Therefore, there is an urgent need for a rapid and sensitive molecular marker. So miR-200a-5p can be used to assist in the diagnosis of PTC at the molecular level, and as a biomarker, can be effectively used to distinguish between PTC and benign thyroid tumor with papillary hyperplasia.
甲状腺乳头状癌（PTC）是最常见的内分泌癌，其发病率近年来显著增加。几种细胞因子，如甲状腺过氧化物酶（TPO）、分化簇 56（CD56）、半乳糖凝集素-3、间皮细胞（MC）、细胞角蛋白 19（CK19）和 BRAF（B-raf）被推荐通过免疫组织化学（IHC）进行明确诊断，但由于其相对较低的敏感性和特异性，仍在临床应用中受到限制。然而，作为一种新的分子生物标志物，microRNA（miRNA）迄今为止尚未得到报道。为了解决这个问题，选择了 miRNA hsa-miR-200a-5p，并通过原位杂交法在伴有乳头状增生的良性甲状腺肿瘤中进行了检测，同时通过 qRT-PCR 检测了新鲜 PTC 组织与对照组中 hsa-miR-200a-5p 的差异表达。还通过免疫组织化学检测了 TPO、CD56、Galectin-3、MC、CK19 和 B-raf 的细胞因子表达水平。使用 SPSS 软件通过 Spearman 方法分析了相关性。正如预期的那样，与对照组相比，PTC 患者的 hsa-miR-200a-5p 表达水平显著升高，并且与 TPO、CD56、Galectin-3、MC、CK19 和 B-raf 一致。此外，hsa-miR-200a-5p 的表达与 TPO（rs=-0.734；：P<0.01）和 CD56（rs=-0.570；：P<0.01）呈负相关，但与 Galectin-3（rs=0.601；：P<0.01）、MC（rs=0.508；：P<0.01）、CK19（rs=0.712；：P<0.01）和 B-raf（rs=0.378；：P<0.01）呈正相关。PTC 和乳头状良性甲状腺乳头状增生在形态学上难以区分，因此需要免疫组织化学进一步鉴别诊断，然而，对于现有的临床常见的免疫组织化学诊断标志物，其敏感性和准确性较低，容易漏诊。因此，迫切需要一种快速、灵敏的分子标志物。因此，miR-200a-5p 可用于在分子水平上协助诊断 PTC，并可作为生物标志物，有效区分 PTC 和伴有乳头状增生的良性甲状腺肿瘤。
