Titov Sergei E, Ivanov Mikhail K, Karpinskaya Elena V, Tsivlikova Elena V, Shevchenko Sergei P, Veryaskina Yulia A, Akhmerova Larisa G, Poloz Tatiana L, Klimova Olesya A, Gulyaeva Lyudmila F, Zhimulev Igor F, Kolesnikov Nikolay N
Institute of Molecular and Cellular Biology, SB RAS, Novosibirsk, Russia.
JSC "Vector-Best", Koltsovo, Russia.
BMC Cancer. 2016 Mar 9;16:201. doi: 10.1186/s12885-016-2240-2.
The postoperative typing of thyroid lesions, which is instrumental in adequate patient treatment, is currently based on histologic examination. However, it depends on pathologist's qualification and can be difficult in some cases. Numerous studies have shown that molecular markers such as microRNAs and somatic mutations may be useful to assist in these cases, but no consensus exists on the set of markers that is optimal for that purpose. The aim of the study was to discriminate between different thyroid neoplasms by RT-PCR, using a limited set of microRNAs selected from literature.
By RT-PCR we evaluated the relative levels of 15 microRNAs (miR-221, -222, -146b, -181b, -21, -187, -199b, -144, -192, -200a, -200b, -205, -141, -31, -375) and the presence of BRAF(V600E) mutation and RET-PTC1 translocation in surgically resected lesions from 208 patients from Novosibirsk oblast (Russia) with different types of thyroid neoplasms. Expression of each microRNA was normalized to adjacent non-tumor tissue. Three pieces of lesion tissue from each patient (39 goiters, 41 follicular adenomas, 16 follicular thyroid cancers, 108 papillary thyroid cancers, 4 medullary thyroid cancers) were analyzed independently to take into account method variation.
The diagnostic classifier based on profiling of 13 microRNAs was proposed, with total estimated accuracy varying from 82.7 to 99% for different nodule types. Relative expression of six microRNAs (miR-146b, -21, -221, -222, 375, -199b) appeared significantly different in BRAF(V600E)-positive samples (all classified as papillary thyroid carcinomas) compared to BRAF(V600E)-negative papillary carcinoma samples.
The results confirm practical feasibility of using molecular markers for typing of thyroid neoplasms and clarification of controversial cases.
甲状腺病变的术后分型对患者的充分治疗至关重要，目前基于组织学检查。然而，这取决于病理学家的资质，并且在某些情况下可能具有难度。大量研究表明，诸如微小RNA和体细胞突变等分子标志物可能有助于此类情况，但对于为此目的而言最佳的标志物组合尚无共识。本研究的目的是通过逆转录聚合酶链反应（RT-PCR），使用从文献中选取的一组有限的微小RNA来区分不同的甲状腺肿瘤。
通过RT-PCR，我们评估了15种微小RNA（miR-221、-222、-146b、-181b、-21、-187、-199b、-144、-192、-200a、-200b、-205、-141、-31、-375）的相对水平以及BRAF（V600E）突变和RET-PTC1易位在来自俄罗斯新西伯利亚州的208例患有不同类型甲状腺肿瘤的患者手术切除病变中的存在情况。将每个微小RNA的表达水平标准化至相邻的非肿瘤组织。对每位患者的三块病变组织（39例甲状腺肿、41例滤泡性腺瘤、16例滤泡状甲状腺癌、108例乳头状甲状腺癌、4例髓样甲状腺癌）进行独立分析，以考虑方法差异。
提出了基于13种微小RNA谱分析的诊断分类器，不同结节类型的总估计准确率在82.7%至99%之间。与BRAF（V600E）阴性的乳头状癌样本相比，六种微小RNA（miR-146b、-21、-221、-222、375、-199b）在BRAF（V600E）阳性样本（均分类为乳头状甲状腺癌）中的相对表达明显不同。
结果证实了使用分子标志物对甲状腺肿瘤进行分型以及澄清有争议病例的实际可行性。
