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Quan Li,* Wen-Xu Jin,* Yi-Xiang Jin, Zhou-Ci Zheng, Xiao-Fen Zhou, Qing-Xuan Wang, Dan-Rong Ye, Yi-Han Sun, Xiao-Hua Zhang, Ou-Chen Wang, En-Dong Chen, Ye-Feng Cai Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China *These authors contributed equally to this work Aim: To investigate the clinical effects of MUC1 on papillary thyroid cancer (PTC) and explore the relationship between MUC1 expression and BRAF mutation. Methods: The data of 69 patients subjected to fine-needle aspiration biopsy in our hospital and 486 patient data downloaded from The Cancer Genome Atlas (TCGA) database were used. Univariate and multivariate analyses were performed.Results: The results on the 486 patients recorded in the TCGA indicated that high MUC1 expression was independently related to BRAF mutation, lymph node metastasis (LNM), and unifocal type. In the 69 fine-needle aspiration biopsy patients with PTC, high MUC1 expression was significantly related to LNM and extrathyroid extension (ETE). The result of Pearson’s correlation coefficient showed that BRAF mutation and MUC1 expression were moderately correlated. Moreover, in the subgroup with low MUC1 expression, the patients with BRAF mutation had higher ETE frequency and LNM than those without BRAF mutation. In the subgroup with BRAF mutation, patients with high MUC1 expression exhibited higher ETE frequency than those with low MUC1 expression, and high MUC1 expression occurred in older patients. In the subgroup with BRAF wild-type mutation, patients with high MUC1 expression had a higher incidence of ETE and LNM than those with low expression.Conclusion: We demonstrated that the MUC1 is an important oncogene in PTC and may have great significance on therapeutic cancer vaccine development.Keywords: MUC1, BRAF mutation, papillary thyroid cancer, prognosis, lymph node metastasis, extrathyroid extension

Zhou-Ci Zheng,* Qing-Xuan Wang,* Wei Zhang, Xiao-Hua Zhang, Du-Ping Huang Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China *These authors contributed equally to this work Background: In contrast to the excellent prognosis for papillary thyroid carcinoma (PTC), the high incidence of lymph node metastasis (LNM) markedly increases the risk of recurrence and secondary surgery. Thus, novel biomarkers must be urgently identified to assess LNM for patients with PTC. NCOA5 is deeply involved in the progression of human cancer; however, its role in thyroid cancer remains unknown.Patients and methods: Quantitative real-time polymerase chain reaction was conducted to investigate the expression of NCOA5 in PTC. RNA-seq data from The Cancer Genome Atlas (TCGA) database were downloaded to further understand the role of NCOA5 in PTC and its relationship with LNM.Results: NCOA5 was significantly downregulated in PTC tissues when compared with that in adjacent noncancerous thyroid tissues both in our local cohort and TCGA database. Reduced expression of NCOA5 was significantly associated with aggressive clinicopathological features, including histological type, tumor stage, BRAF-V600E mutation, LNM, extrathyroid extension, and clinical stage. Moreover, logistic analysis indicated that reduced expression of NCOA5, age, histological type, and clinical stage are independent high-risk factors for LNM in PTC.Conclusion: Our study provides new insights and evidence that NOCA5 was significantly correlated with the progression of PTC and was particularly involved in LNM. Keywords: thyroid cancer, NCOA5, lymph node metastasis&nbsp

Clinicians are confronted with an increasing number of patients with thyroid nodules. Reliable preoperative diagnosis of thyroid nodules remains a challenge because of inconclusive cytological examination of fine-needle aspiration biopsies. Although molecular analysis of thyroid tissue has shown promise as a diagnostic tool in recent years, it has not been successfully applied in routine clinical use, particularly in Chinese patients.Whole-transcriptome sequencing of 19 primary papillary thyroid cancer (PTC) samples and matched adjacent normal thyroid tissue (NT) samples were performed. Bioinformatics analysis was carried out to identify candidate diagnostic genes. Then, RT-qPCR was performed to evaluate these candidate genes, and four genes were finally selected. Based on these four genes, diagnostic algorithm was developed (training set: 100 thyroid cancer (TC) and 65 benign thyroid lesions (BTL)) and validated (independent set: 123 TC and 81 BTL) using the support vector machine (SVM) approach.We discovered four genes, namely fibronectin 1 (FN1), gamma-aminobutyric acid type A receptor beta 2 subunit (GABRB2), neuronal guanine nucleotide exchange factor (NGEF) and high-mobility group AT-hook 2 (HMGA2). A SVM model with these four genes performed with 97.0 % sensitivity, 93.8 % specificity, 96.0 % positive predictive value (PPV), and 95.3 % negative predictive value (NPV) in training set. For additional independent validation, it also showed good performance (92.7 % sensitivity, 90.1 % specificity, 93.4 % PPV, and 89.0 % NPV).Our diagnostic panel can accurately distinguish benign from malignant thyroid nodules using a simple and affordable method, which may have daily clinical application in the near future.

Qing-Xuan Wang, En-Dong Chen, Ye-Feng Cai, Yi-Li Zhou, Zhou-Ci Zheng, Ying-Hao Wang, Yi-Xiang Jin, Wen-Xu Jin, Xiao-Hua Zhang, Ou-Chen Wang Department of Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China Purpose: Thyroid cancer is the most frequent malignancies of the endocrine system, and it has became the fastest growing type of cancer worldwide. Much still remains unknown about the molecular mechanisms of thyroid cancer. Studies have found that some certain relationship between ARAP3 and human cancer. However, the role of ARAP3 in thyroid cancer has not been well explained. This study aimed to investigate the role of ARAP3 gene in papillary thyroid carcinoma. Methods: Whole exon sequence and whole genome sequence of primary papillary thyroid carcinoma (PTC) samples and matched adjacent normal thyroid tissue samples were performed and then bioinformatics analysis was carried out. PTC cell lines (TPC1, BCPAP, and KTC-1) with transfection of small interfering RNA were used to investigate the functions of ARAP3 gene, including cell proliferation assay, colony formation assay, migration assay, and invasion assay. Results: Using next-generation sequence and bioinformatics analysis, we found ARAP3 genes may play an important role in thyroid cancer. Downregulation of ARAP3 significantly suppressed PTC cell lines (TPC1, BCPAP, and KTC-1), cell proliferation, colony formation, migration, and invasion. Conclusion: This study indicated that ARAP3 genes have important biological implications and may act as a potentially drugable target in PTC. Keywords: papillary thyroid carcinoma, next-generation sequence, ARAP3, oncogene

This study aims to investigate the impact of psammoma body (PB) on papillary thyroid carcinoma (PTC), and evaluate the association among PB, Hashimoto thyroiditis (HT), and other clinicopathologic characteristics in PTC patients. We conducted a retrospective case-control study involving 1052 PTC patients who underwent total thyroidectomy or lobectomy with lymph node dissection. Psammoma body was observed in 324 out of 1052 PTC (30.8%) patients. Ultrasonographic (US) calcification (P