Predictive Factors of Skip Metastasis in Papillary Thyroid Cancer.

BACKGROUND Skip metastasis is defined as metastasis incident to the lateral compartment without involvement of the central compartment, and is generally unpredictable in papillary thyroid cancer (PTC). The present study aimed to investigate the frequency and predictor value of skip metastasis in PTC patients. MATERIAL AND METHODS A total of 355 patients diagnosed with thyroid cancer who had received a prior complete thyroidectomy with bilateral central neck and ipsilateral lateral neck lymph node dissection were enrolled in this study. The clinicopathological and ultrasound features were analyzed. A univariate and multivariate analysis were performed to identify the risk factors of skip metastasis. RESULTS The frequency of skip metastasis was 12.4% (44/355). The PTC patients with skip metastasis exhibited fewer lymph node metastasis, which was more commonly detected in tumor size ≤1 cm (OR 9.354; p=0.001; 95% confidence interval (CI) 1.865-26.735), tumors located in upper pole (OR 3.822; p<0.001; 95% CI 1.935-7.549), without a well-defined margin (OR 2.528; p=0.016; CI 1.191-5.367), and extrathyroidal extension (OR 2.406; p=0.013; CI 1.691-4.367). CONCLUSIONS Skip metastasis was common in PTC. The PTC patients with a tumor size ≤1.0 cm, located in the upper pole, without a well-defined margin and extrathyroidal extension should be carefully evaluated for skip metastasis.

Downregulation of CD44v6 Enhances Chemosensitivity by Promoting Apoptosis and Inhibiting Autophagy in Colorectal Cancer HT29 Cells.

BACKGROUND: Chemotherapy resistance reduces the effectiveness of chemotherapeutic drugs greatly, resulting in treatment failure. Therefore, exploring chemoresistance-related genes and the corresponding mechanism is extremely important. The central role of CD44v6 in colorectal cancer has been previously reported. However, the effects of CD44v6 gene knockdown on the chemosensitivity of colorectal cancer cells are not conclusive. MATERIAL AND METHODS: A stable CD44v6 knockdown cell model in HT29 cells (HT29-KD) was established via lentiviral transduction. A quantitative real-time polymerase chain reaction (PCR) was carried out to confirm the knockdown efficiency. The chemosensitivity of cells to 5-fluorouracil (5-FU) was determined by a cell counting kit (CCK)-8 assay. Cell apoptosis and the cell cycle were assessed by flow cytometry. RESULTS: The CD44v6 knockdown cell model was successfully constructed by using lentiviral transduction. Upon treatment with 5-FU, the inhibitory rate for cell activity of HT29-KD cells was significantly higher than that of the control group (HT29-NC). CD44v6 gene knockdown did not significantly affect HT-29 cell proliferation, according to the CCK-8 assay and cell cycle analysis. The cell apoptosis assay revealed that CD44v6 gene knockdown promoted HT-29 cell apoptosis. Without 5-FU treatment, there was no significant difference in terms of the relative expression level of the autophagy-related gene BECN1 between the two groups. However, with 5-FU treatment, the relative expression level of BECN1 in HT29-KD cells was much lower than that in HT29-NC cells. CONCLUSION: Our study confirms that CD44v6 gene knockdown can enhance chemosensitivity in HT29 cells by promoting apoptosis and inhibiting autophagy, thus affirming the effects of CD44v6 on the chemosensitivity of colorectal cancer.

Up-Regulated AKR1C2 is correlated with favorable prognosis in thyroid carcinoma.

Purpose: Aldo-keto reductase family 1, member C2 (AKR1C2) gene encodes for a member of the AKR superfamily and participates in the metabolism of various drugs. Moreover, tumor and normal tissues exhibit an evident difference in the expression level of this gene. Methods: We downloaded and analyzed AKR1C2 expression level and the data consisting of the clinicopathological features of 490 papillary thyroid carcinoma (PTC) tumor tissues and 59 normal thyroid tissues from The Cancer Genome Atlas (TCGA) cohort. Diverse statistical methods, such Chi-square test, univariate and multivariate Cox regression analyses, and Kaplan-Meier survival curves were used. We down-/up-regulated the expression of AKR1C2 and explored its specific role in thyroid cancer cell lines by utilizing the si-RNA and plasmid. Results: We divided all patients who were collected in TCGA data sets into under-expressed (n = 245) and over-expressed groups (n = 245). We subsequently analyzed the data and obtained the following findings: (a) AKR1C2 is down-regulated in papillary thyroid carcinoma (PTC) (p<0.001), (b) Kaplan-Meier result revealed that high expression level of AKR1C2 are correlated with favorable survival in PTC (p = 0.043), and (c) factors independently associated with recurrence-free survival are AKR1C2 expression (hazard ratio (HR 0.819) and American Joint Committee on Cancer (AJCC) stage (HR 1.534). We also analysed the relationship between AKR1C2 expression and clinicopathological features in the validated cohort. AKR12C under-expression correlated with lymph node metastasis (p = 0.009) and AJCC stage (p= 0.001) which might indicate AKR12C as a prognostic factor in PTC. The cell line experiment results showed that the knockdown and overexpression of AKR1C2 significantly enhance and weaken the abilities of migration and invasion in papillary thyroid carcinoma cell. Conclusion: Our results indicated that AKR1C2 exerts inhibitory effects on PTC oncogenesis and elevated AKR1C2 expression is associated with the favorable prognostic factors and recurrence free survival.

Prediction of central lymph node metastasis in papillary thyroid microcarcinoma according to clinicopathologic factors and thyroid nodule sonographic features: a case-control study.

BACKGROUND: Preoperative diagnosis of central lymph node metastasis (CLNM) poses to be a challenge in clinical node-negative papillary thyroid microcarcinoma (PTMC). This research work aims at investigating the association existing between BRAF mutation, clinicopathological factors, ultrasound characteristics, and CLNM, in addition to establishing a predictive model for CLNM in PTMC. MATERIALS AND METHODS: The study included 673 PTMC patients, already undergone total thyroidectomy or lobectomy with prophylactic central lymph node dissection. The predictor factors were identified through univariate and multivariate analyses. The support vector machine was put to use to develop statistical models, which could predict CLNM on the basis of independent predictors. RESULTS: Tumor size (>5 mm), lower location, no well-defined margin, contact of >25% with the adjacent capsule, display of enlarged lymph nodes, and BRAF mutation were independent predictors of CLNM. Through the use of the predictive model, 79.6% of the patients were classified accurately, the sensitivity and specificity amounted to be 85.1% and 75.8%, respectively, and the positive predictive value and negative predictive value stood at 71.6% and 87.6%, respectively. CONCLUSIONS: We established a predictive model in order to predict CLNM preoperatively in PTMC when preoperative diagnosis of CLNM was not clear.

Clinical effect of MUC1 and its relevance to BRAF V600E mutation in papillary thyroid carcinoma: a case-control study.

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.