A potential biomarker hsa-miR-200a-5p distinguishing between benign thyroid tumors with papillary hyperplasia and papillary thyroid carcinoma

Abstract

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.

Downregulation of miR‑193a‑3p via targeting cyclin D1 in thyroid cancer

“…A number of studies have reported that intricate biological processes participating in the interactions between polygenes may contribute to the occurrence and progression of TC ( 10 – 12 ). Previous studies have suggested that hsa-miR-200a-5p and hsa-miR-181a-2-3p could be applied for latent diagnostic and prognostic biomarkers of TC ( 13 , 14 ). Nevertheless, the clinical characteristics of molecular profiles in TC have yet to be elucidated.…”

Genome-Wide Identification and Analysis of Enhancer-Regulated microRNAs Across 31 Human Cancers

“…In addition, miR-200a, as a target of the enhancer, was highly relevant to the survival of thyroid cancer patients ( Figure 5B ). A previous study has shown that miR-200a regulates the epithelial stromal transformation of thyroid cancer through the EGF/EGFR signal ( Xue et al, 2015 ), and it is a key factor in the epithelial phenotype and a tumor suppressor in THCA ( Wang et al, 2018 ). Additionally, the survival analysis showed that patients with low expression of miR-200a have a lower survival time.…”

Identification of miR-200a-5p targeting the peptide transporter TAP1 and its association with the clinical outcome of melanoma patients

“…42,43 Moreover, miR-200a-5p overexpression has recently been described in non-small cell lung cancer (NSCLC), 44 ovarian cancer, 45 breast cancer 46 and papillary thyroid carcinoma, but so far not linked to HLA-I and APM component expression. 47 Alterations in the surface expression and/or function of the HLA-I antigens are frequently found in human tumors and equip neoplastic cells with mechanisms to escape immune surveillance. 5 Furthermore, tumors with acquired resistance to checkpoint inhibitor therapy or adoptive T cell transfer can acquire genetic deficiencies or downregulation of APM components resulting in the loss or reduced expression of either constitutive or HLA-I surface antigens.…”

“… 42 , 43 Moreover, miR-200a-5p overexpression has recently been described in non-small cell lung cancer (NSCLC), 44 ovarian cancer, 45 breast cancer 46 and papillary thyroid carcinoma, but so far not linked to HLA-I and APM component expression. 47 …”