Carcinoma, Papillary/genetics* ; Gene Expression Regulation, Neoplastic ; Humans ; RNA, Long Noncoding/genetics* ; Thyroid Cancer, Papillary/genetics* ; Thyroid Neoplasms/genetics*

Antiporters/genetics* ; Carcinoma, Papillary/pathology* ; Humans ; Neoplasm Metastasis/genetics* ; Sulfate Transporters/genetics* ; Thyroid Cancer, Papillary/pathology* ; Thyroid Neoplasms/pathology*

Carcinoma, Papillary ; genetics ; Humans ; Mutation ; Proto-Oncogene Proteins B-raf ; genetics ; Thyroid Neoplasms ; genetics

Carcinoma, Papillary ; diagnosis ; genetics ; Female ; Humans ; Male ; Middle Aged ; Pedigree ; Thyroid Neoplasms ; diagnosis ; genetics

In recent years, with the improvement of the sensitivity of examination equipment and the change of people's living environment and diet, the rate of thyroid cancer has risen rapidly, which has increased nearly five folds in 10 years. The pathogenesis, clinical manifestation, biological behavior, treatment and prognosis of thyroid carcinoma of different pathological types are obviously different. Papillary thyroid carcinoma (PTC) can develop at any age, which accounts for about 90% of thyroid cancer. It progresses slowly and has favourable prognosis, but lymph node metastasis appears easily. Whether PTC is accompanied by lymph node metastasis has an important impact on its prognosis and outcome. The Raf murine sarcoma viral oncogene homolog B(BRAF)gene mutation plays a crucial role in PTC lymph node metastasis. Having an in-depth understanding of the specific role and mechanism of BRAF gene mutation in PTC is expected to provide new ideas for diagnosis and treatment of PTC.
Animals ; Carcinoma, Papillary/genetics* ; Humans ; Lymphatic Metastasis ; Mice ; Mutation ; Oncogenes ; Proto-Oncogene Proteins B-raf/genetics* ; Thyroid Cancer, Papillary/genetics* ; Thyroid Neoplasms/genetics*

Objective: To investigate the effect of centrosomal protein Cep63 on the apoptosis of papillary thyroid carcinoma (PTC) cell lines TPC-1 and underlying mechanism. Methods: With collected PTC tissues and adjacent tissues, Cep63 expression was detected by RT-qPCR and its relationship with clinicopathological factors was analyzed. The experiment included negative control group (NC), low expression group (Cep63(-)) and overexpression group (Cep63(+)), and wild-type TPC-1 cells were transfected with Cep63 lentivirus. The efficiency of Cep63 was detected by western blot (WB) and qRT-PCR. Cell proliferation ability was detected by plate cloning experiment and MTT assay. Cell apoptotic rate was detected by flow cytometry, and expression levels of apoptosis-related proteins were detected by immunohistochemistry and WB. The t-test was used to compare the differences in the means between the two groups, the one-way analysis of variance was used to compare multiple groups, and the chi-square test was used to analyze the association between gene expression levels and pathological factors. Results: Compared with NC group, cell proliferation ability was significantly decreased in Cep63(-) group (3.18±0.07 vs. 2.14±0.09, t=8.54, P<0.01) and significantly increased in Cep63(+) group (3.18±0.07 vs. 3.58±0.10, t=3.21, P<0.05). Apoptotic rates in NC, Cep63 (-) and Cep63 (+) groups were respectively 3.03%±0.24%, 8.66%±0.44% and 1.17%±0.44%, and the flow cytometry showed that the low expression of Cep63 significantly increased the apoptosis TPC-1 cells (F=157.7, P<0.001). Bcl-2 protein expression levels of NC, Cep63 (-) and Cep63 (+) groups were respectively 1.07±0.03, 0.49±0.01 and 1.99±0.09, and BAX protein expression levels of three groups were respectively 0.64±0.02, 1.06±0.01 and 0.21±0.03. WB showed that the expression level of Bcl-2 decreased (F=183.2, P<0.001), while the expression level of BAX was significantly up-regulated (F=283.7, P<0.001). Conclusion: Cep63 may regulate the apoptotic process of TPC-1 cells through Bcl-2/BAX pathway and Cep63 may be a potential oncogene of PTC.
Apoptosis ; Carcinoma, Papillary/genetics* ; Cell Cycle Proteins ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Humans ; Thyroid Cancer, Papillary/genetics* ; Thyroid Neoplasms/genetics*

OBJECTIVETo investigate the correlation of microRNA-155 (miR-155) expression with clinicopathological features of patients with papillary thyroid carcinoma (PTC) and explore the value of miR-155 in prognostic assessment of PTC.

METHODSWe collected 86 pairs of fresh PTC and adjacent tissues to examine the expression of miR-155 using fluorescent quantitative PCR. miR-155 expressions in the tissues were analyzed in relation to the clinicopathological features of the patients.

RESULTSCompared with the paired adjacent tissues, 69.8% (60/86) of the PTC tissues showed up-regulated miR-155 expression by 2.63∓2.73 folds. Up-regulated miR-155 expressions were associated with a larger tumor size (1.66∓0.96 vs 1.19∓0.52 cm, P=0.021), a higher likeliness of extrathyroid invasion (56.7% vs 23.1%, P=0.004), a higher rate of lymph node metastasis (70% vs 46.2%, P=0.036), a more advanced TNM stage, and a higher rate of III-IV stage of the tumor (20% vs 0%, P=0.014). The expression level of miR-155 in PTC tissues was positively correlated with lymph node metastasis (r=0.531, P=0.001).

CONCLUSIONPTC patients with miR-155 over-expression tend to have a greater tumor size, a greater likeliness of extrathyroid involvement, a higher rate of cervical lymph node metastasis and a more advanced TNM stage. The high expression of miR-155 in the tumor may indicate a poor prognosis of PTC patients.

Carcinoma, Papillary ; genetics ; Humans ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; MicroRNAs ; genetics ; Neck ; Prognosis ; Thyroid Neoplasms ; genetics ; Up-Regulation

Objective:To analyze the clinical significance of multigene assay in papillary thyroid carcinoma（PTC）. Methods:Patients who underwent thyroidectomy in a tertiary hospital from August 2021 to May 2022 were enrolled. The eight-gene panel was used to detect the tumor tissue of patients, and the correlation between gene mutations and clinical features was analyzed. Results:Among 161 patients, mutation rate of BRAF V600E, RET/PTC1 and TERT promotor were 82.0%, 6.8% and 4.3%, respectively. BRAF V600E mutation was more common in male patients（P=0.023）. TERT promotor-mutated tumors had a large diameter（P=0.019）, a high proportion of multifocal lesions（P=0.050）, and a large number of lymph node metastases（P=0.031）. Among 89 patients who completed preoperative BRAF detection, there was a strong consistency between the preoperative aspiration test and postoperative panel（Cohen κ=0.694, 95%CI: 0.482-0.906, P<0.01）. In the hematoxylin-eosin sections obtained from 80 patients, BRAF V600E was still the main type of gene mutation, and the classical/follicular type was more distributed. TERT promotor and RET/PTC1 mutation were the main genetic events for tall-cell/columnar/hobnail type and diffuse sclerosing type, respectively. One-way ANOVA showed that there were differences in diagnosis age（P=0.029） and tumor size（P<0.01） among different pathological types. Conclusion:As a simple and feasible clinical detection method for PTC, the multigene assay can supplement the identification of important genetic events other than BRAF V600E, and provide more prognostic information and follow-up hints for postoperative patients.
Humans ; Male ; Thyroid Cancer, Papillary/genetics* ; Thyroid Neoplasms/pathology* ; Proto-Oncogene Proteins B-raf/genetics* ; Clinical Relevance ; Carcinoma, Papillary/pathology* ; Mutation

OBJECTIVE: To explore the effect on proliferation and invasion of human papillary thyroid carcinoma K1 cells by application of small hairpin RNA (shRNA) silencing TFF3 gene expression. METHOD: Using liposome transfection method, TFF3-shRNA targeting of TFF3 gene will be transient transfected to papillary thyroid carcinama K1 cells, inducing the corresponding gene silencing. The experiment set up blank control group (Con group), negative control group (ConNC group) and interference group (TFF3-shRNA group). The TFF3 protein and mRNA expression were evaluated by RT-PCR, Real time-PCR, immunocytochemistry and Western blot in K1 cells after TFF3-shRNA transfected. CCK-8 method and Scratch test were used to detect the change of proliferation ability and invasion ability respectively. RESULT: (1) The recombinant plasmid Ca # HSH018037-4-HIVmU6 carrying TFF3-shRNA transfected K1 cells successfully. (2) RT-PCR and Real time-PCR detected the expression of TFF3 mRNA, which was 0.38 ± 0.11 times as many as the blank control group (P < 0.01) after TFF3 gene silenced. But the negative control group was 1.082 times of blank control group (P > 0.05). (3) Western blot show that after TFF3 gene silence induced TFF3 protein expression levels have decreased 59.5% (P < 0.01), The difference was statistically significant compared with the blank control group. (4) Cell scratch detects K1 cell invasion ability. The invasion ability of K1 cells in interference group (TFF3-shRNA group) reduced. The scratch width significantly decreased 57.1% than blank control group (P < 0.01). (5) CCK-8 kit detect cell proliferation ability. K1 cells grow significantly slower in the interference group (TFF3-shRNA group) than the blank control group through the analysis of the growth curve (P < 0.01). In the interference group (TFF3-shRNA group) proliferation inhibition rate of K1 cells at 6 h, 12 h, 24 h and 36 h, 48 h are 16.6%, 26.6%, 33.6%, 33.8%, 35.0% respectively. Compared with negative control group, proliferation ability of K1 cell decreased significantly. CONCLUSION Silenced TFF3 gene can cause the degradation of mRNA, reduce the protein translation , and inhibit the invasion and proliferation ability of K1 cell.
Carcinoma ; genetics ; pathology ; Carcinoma, Papillary ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Peptides ; genetics ; Plasmids ; RNA Interference ; RNA, Messenger ; genetics ; RNA, Small Interfering ; genetics ; Real-Time Polymerase Chain Reaction ; Thyroid Cancer, Papillary ; Thyroid Neoplasms ; genetics ; pathology ; Transfection ; Trefoil Factor-3

BACKGROUNDPapillary thyroid carcinoma (PTC) represents one of the most frequent endocrine malignancies. Several factors have been found to be involved in determining the outcome of treatment for patients with PTC. Large tumor size, diagnosis at an early age, extra-thyroidal invasion, aggressive histological variants, and distant metastases are the most important determinants of a poor outcome. BRAF(V600E) mutation has been found to be a major genetic alteration in PTC. This study aimed to evaluate progression in patients with multifocal and solitary PTC.

METHODSWe performed a retrospective study to analyze 368 patients with PTC who underwent surgery, including 282 patients with solitary PTC and 86 patients with multifocal PTC. The status of BRAF(V600E) mutation in all tumor foci from multifocal PTC was detected.

RESULTSOur study suggested that multifocal PTC was more related to lymph node metastasis and vascular invasion than solitary PTC. However, the distant metastasis rate and 10-year survival rate showed no difference between these two groups. The number of tumor foci did not affect progression of disease in multifocal PTC patients. Lymph node metastasis in multifocal PTC patients was associated with larger tumors, diagnosis at early stage, and extra-thyroidal invasion.

CONCLUSIONThe status of BRAF(V600E) mutation was more frequent in multifocal PTC patients with lymph node metastasis and diagnosis at later age.

Adult ; Aged ; Carcinoma ; genetics ; pathology ; Carcinoma, Papillary ; genetics ; pathology ; Female ; Humans ; Male ; Middle Aged ; Mutation ; Proto-Oncogene Proteins B-raf ; genetics ; Retrospective Studies ; Thyroid Neoplasms ; genetics ; pathology