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NONHSAT076754 aids ultrasonography in predicting lymph node metastasis and promotes migration and invasion of papillary thyroid cancer cells.

ABSTRACT: Lymph node metastasis (LNM) is the primary challenge in papillary thyroid cancer (PTC). Recurrent cancerous lymph nodes require repeated surgeries, which increases the risk for surgical complications. Thus, the evaluation of LNM before surgery is important. Ultrasonography is the most convenient way to examine cervical LNM, but the sensitivity of ultrasonography in the identification of LNM in cases of PTC is extremely low. A series of lncRNAs (long noncoding RNAs) have been reported as candidate biomarkers in a variety of tumors. This study detected the lncRNA NONHSAT076754 in PTC and analyzed the correlation of NONHSAT076754 with the clinicopathological and ultrasonographic characteristics of patients with PTC. The value of NONHSAT076754 as an auxiliary diagnostic biomarker for use along with ultrasonography in the differentiation of LNM in PTC was assessed. Additionally, the biological function of NONHSAT076754 in PTC cells was demonstrated. Our study indicated that NONHSAT076754 promotes migration and invasiveness of PTC and serves as a valuable auxiliary biomarker that can be used along with ultrasonography in the prediction of cervical LNM.

SUBMITTER: Xia S

PROVIDER: S-EPMC5356800 | biostudies-other | 2017 Jan

REPOSITORIES: biostudies-other

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NONHSAT076754 aids ultrasonography in predicting lymph node metastasis and promotes migration and invasion of papillary thyroid cancer cells.

Xia Shujun S Wang Chuandong C Ni Xiaofeng X Ni Zhongxin Z Dong Yijie Y Zhan Weiwei W

Oncotarget 20170101 2

Lymph node metastasis (LNM) is the primary challenge in papillary thyroid cancer (PTC). Recurrent cancerous lymph nodes require repeated surgeries, which increases the risk for surgical complications. Thus, the evaluation of LNM before surgery is important. Ultrasonography is the most convenient way to examine cervical LNM, but the sensitivity of ultrasonography in the identification of LNM in cases of PTC is extremely low. A series of lncRNAs (long noncoding RNAs) have been reported as candidat ...[more]

PMID: 27906682

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Project description:The incidence of papillary thyroid carcinoma (PTC) is increasing. Lymph node metastatic status of PTC is a major factor for decision marking of surgery and surgical extend, however, no reliable tool exists for prediction of PTC nodal metastasis, for example, ultrasound cannot qualitatively diagnose and effectively detect central lymph node metastasis (CLNM). Therefore, the development of a new diagnostic biomarker is crucial for CLNM. Metabolic dysregulation is an important factor associated with malignancy and metastasis of tumors. Pyruvate carboxylase (PC) is a major anaplerotic enzyme that catalyzes the carboxylation of pyruvate to form oxaloacetate, which has been suggested to be involved in the tumorigenesis of several cancers, including PTC. This study aimed to explore the role of PC expression in thyroid fine-needle aspiration (FNA) wash-out fluid for predicting CLNM in PTC, and to explore how PC is involved in PTC development. The expression levels of PC in PTC tissues and normal thyroid tissues were first compared based on bioinformatics analysis of public databases, including the Gene Expression Profiling (GEPIA), Oncomine and Gene Expression Omnibus (GEO) databases. Then, the PC mRNA and protein expression levels were measured by RT-PCR and Immunohistochemistry (IHC) in surgical tissues from a total of 42 patients with surgically confirmed PTC, and compared in patients with and without CLNM. Further, to assess PC expression in diagnostic biopsies, a total of 71 thyroid nodule patients with ultrasound-guided FNA wash-out fluid samples and cytological diagnosis were prospectively enrolled in the study. Then, we analyzed the mechanism of PC-mediated PTC progression in vitro. This study showed that PC expression was higher in PTC tissues and thyroid FNA wash-out fluid samples from patients with CLNM than those from patients without CLNM, and that PC-induced PTC metastasis may occur through the TGF-β/Smad-regulated epithelial-mesenchymal transition (EMT) pathway.

Project description:BackgroundDistant metastasis (DM) is a rare event and has a negative effect on the prognosis for papillary thyroid carcinoma (PTC). The relationship between cervical lymph node metastasis and DM is complicated and unclear. This study aimed to evaluate the impact of N stage subclassification on different distant metastasis sites based on age stratification, especially for patients with papillary thyroid microcarcinoma.MethodsA total of 28,712 patient with PTC cases between 2010 and 2018 were extracted from the Surveillance, Epidemiology, and End Results database. Multivariable logistic regression analysis was utilized to adjust for confounding variables. Risk stratification, including positive lymph node number and lymph node ratio, was established by receiver operating characteristic curves to help predict DM.ResultsLung was the most common metastatic site regardless of N0, N1a disease, or N1b disease. As the N stage increased, the higher the rate of DM identified. After age stratification, only N1b disease significantly increased the risk of lung metastasis (LM; odds ratio, OR = 20.45, P < 0.001) rather than bone metastasis (BM; OR = 3.46, P > 0.05) in younger patients. However, in older patients, N1b disease significantly increased the risk of both LM (OR = 4.10, P < 0.001) and BM (OR = 2.65, P = 0.007). In patients with papillary thyroid microcarcinoma (PTMC), N1a disease did not increase the risk of DM, LM, and BM compared with N0 disease (P > 0.05). Furthermore, combined N stage with risk stratification has well performance in predicting DM (area under the curve, AUC = 0.761). Similar results were shown in PTC patients with LM (AUC = 0.770) and BM (AUC = 0.729).ConclusionOverall, the incidence of DM significantly increased with the progress of N disease after age stratification. N1a disease did not increase the risk of DM in PTMC patients, regardless of LM or BM. Combined N stage with risk stratification may be beneficial for DM prediction.

Dataset Information

NONHSAT076754 aids ultrasonography in predicting lymph node metastasis and promotes migration and invasion of papillary thyroid cancer cells.

Publications

NONHSAT076754 aids ultrasonography in predicting lymph node metastasis and promotes migration and invasion of papillary thyroid cancer cells.

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