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Problems solved by technology
[0005] The mutation frequency of BRAF, RET / PTC, RAS, Pax8 / PPA gamma, P53 and other genes proposed as biomarkers of thyroid follicular carcinoma is not high, and in fact cannot be practically applied in diagnosis
In addition, studies that confirmed that the expression levels of 5 genes, ELMO1, EMCN, ITIH5, KCNAB1, and SLCO2A1, were decreased in thyroid follicular carcinoma tissues compared with follicular adenoma tissues, although it has disclosed that it is possible to develop a method to distinguish follicular thyroid carcinoma from A marker of follicular adenoma, but it must go through the process of extracting mRNA from tissue before it can be used as a marker, so there are great limitations (Pfeifer et al. BMC Medical Genomics, 2013, 6:380)
Although various protein markers for judging thyroid cancer are used in immunohistochemistry (immunohistochemistry) (Wiseman SM et al., Annals of Surgical Oncology, 2008, 15: 2811-2826), the specificity is low and almost no Potential for distinguishing follicular carcinoma of the thyroid from follicular adenoma
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Embodiment 1
[0080] Biotype identification of thyroid tissue proteins
[0081] A total of 2,909 protein classes were identified in follicular adenoma tissue and 2,739 protein classes were identified in follicular thyroid carcinoma tissue respectively, for a total of 4,162 proteins ( figure 1 ) for biological identification. This is unprecedented in academia to date, and is the result of the most extensive protein analysis of thyroid cancer.
Embodiment 2
[0083] Gene Ontology Analysis
[0084] The results of Gene Ontology analysis showed that the functional classification of various proteins related to oxidation / reduction, protein localization, and intracellular transport in the follicular adenoma patient group samples was obvious (List 2), but in the follicular thyroid carcinoma patient group, proteolysis However, the functional classification of proteins involved in the decomposition of macromolecules, RNA processing, and cell cycle is different (Table 1).
[0085] 【List 1】
[0086]
[0087] 【List 2】
[0088]
[0089] Especially among the proteins specifically expressed in the thyroid tissue of follicular carcinoma of the thyroid gland, the increase of the proteins related to the adhesion plaque was more significant than that of the thyroid tissue of follicular adenoma. It was also shown that proteins associated with the spliceosome are specifically increased in follicular thyroid carcinoma.
Embodiment 3
[0091] Analysis of protein expression tendency related to aminoacyl-tRNA synthetase (ARS)
[0092] Among the proteins identified by the biological category using the analysis results, after identifying the proteins associated with ARS, standard-free semi-quantitative analysis was performed based on the peak area. The results showed that 20 ARSs and AIMPs in follicular adenoma tissue and 21 ARS and AIMP in thyroid follicular carcinoma tissue were confirmed, and the quantitative analysis results are shown in the following table (List 3, List 4).
[0093] 【List 3】
[0094]
[0095] 【List 4】
[0096]
[0097] In particular, in follicular carcinoma of the thyroid tissue, AARS (Alanine-tRNA ligase) decreased, AIMP1 (aminoacyl-tRNA synthetase complex-interacting multifunctional protein 1), KARS (lysine-tRNA ligase) and VARS (valine-tRNA ligase) increased ( figure 2 , image 3 ). This study demonstrated for the first time that AIMP1 and KARS were increased in thyroid fol...
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Abstract
The present invention relates to a method for detecting markers for diagnosis of follicular thyroid carcinoma using an expression level of aminoacyl-tRNA synthetase-related protein. More specifically,the present invention relates to a method for detecting markers of follicular thyroid carcinoma in order to provide information necessary for the diagnosis of follicular thyroid carcinoma in a patient suspected of having follicular thyroid carcinoma, the method comprising: (a) a step of providing a sample from a subject suspected of having follicular thyroid carcinoma; (b) a step of measuring theprotein expression level of an aminoacyl-tRNA synthetase or an aminoacyl-tRNA synthetase complex-interacting multifunctional protein in the sample; and (c) a step of comparing the measured protein expression level with that of a control, and determining that the subject having a confirmed change in the protein expression level has follicular thyroid carcinoma. Specifically, the types of proteinsdisclosed in the present invention can be used to diagnose follicular thyroid carcinoma simply and clearly without surgical tissue retrieval, and have high diagnostic sensitivity and specificity.
Description
technical field [0001] The present invention relates to a method for detecting diagnostic markers of follicular thyroid carcinoma (follicular thyroid carcinoma) using aminoacyl-tRNA synthetase-related protein expression levels, in particular to a method for detecting markers of follicular thyroid carcinoma, for Provide the information required for the diagnosis of thyroid follicular carcinoma in patients with suspected thyroid follicular carcinoma, including the steps of: (a) providing samples from subjects suspected of thyroid follicular carcinoma; (b) detecting aminoacyl-tRNA synthetase (aminoacyl e) of -tRNA synthetas or the protein expression level of aminoacyl-tRNA synthetase complex-interacting multifunctional protein; and (c) compare the protein expression level detected above with the comparison group In comparison, it is judged that the subject whose protein expression level has changed has follicular thyroid carcinoma. Background technique [0002] This applicatio...
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