Postgraduate Program of Basic and Applied Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, Brazil.
Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada.
Int J Mol Sci. 2023 Aug 5;24(15):12459. doi: 10.3390/ijms241512459.
As BRAF, TERT, HLA-G, and microRNAs have been individually associated with papillary thyroid carcinoma (PTC), we aimed to evaluate the individual and collaborative role of these markers in PTC in the same patient cohort. HLA-G and BRAF tumor expression was evaluated by immunohistochemistry. Using molecular methods, BRAF and promoter mutations were evaluated in thyroid fine needle aspirates. MicroRNA tumor profiling was investigated using massively parallel sequencing. We observed strong HLA-G (67.96%) while BRAF (62.43%) staining was observed in PTC specimens. BRAF overexpression was associated with poor response to therapy. The BRAF (52.9%) and (13%) mutations were associated with extrathyroidal extension, advanced-age, and advanced-stage cancer. The rs2853669 CC+TC genotypes (38%) were overrepresented in metastatic tumors. Nine modulated microRNAs targeting the and/or genes were observed in PTC and involved with cancer-related signaling pathways. The markers were individually associated with PTC features, emphasizing the synergistic effect of BRAF and ; however, their collaborative role on PTC outcome was not fully demonstrated. The differentially expressed miRNAs targeting the and/or genes may explain their increased expression in the tumor milieu.
由于 BRAF、TERT、HLA-G 和 microRNAs 分别与甲状腺乳头状癌(PTC)相关,我们旨在评估这些标志物在同一患者队列中对 PTC 的单独和协同作用。通过免疫组织化学评估 HLA-G 和 BRAF 肿瘤表达。使用分子方法,评估甲状腺细针抽吸物中的 BRAF 和 启动子突变。使用大规模平行测序研究 microRNA 肿瘤谱。我们观察到 PTC 标本中存在强烈的 HLA-G(67.96%)和 BRAF(62.43%)染色。BRAF 过表达与治疗反应不良相关。BRAF(52.9%)和 (13%)突变与甲状腺外延伸、高龄和晚期癌症相关。rs2853669 CC+TC 基因型(38%)在转移性肿瘤中过度表达。在 PTC 中观察到 9 种针对 和/或 基因的调节 microRNAs,涉及癌症相关信号通路。这些标志物分别与 PTC 特征相关,强调了 BRAF 和 的协同作用;然而,它们对 PTC 结果的协同作用尚未完全证明。针对 和/或 基因的差异表达 microRNAs 可能解释了它们在肿瘤微环境中表达增加的原因。