Upregulation of the solute carrier family 7 genes is indicative of poor prognosis in papillary thyroid carcinoma.

BACKGROUND: The solute carrier (SLC) 7 family genes comprise 14 members and function as cationic amino acid/glycoprotein transporters in many cells, they are essential for the maintenance of amino acid nutrition and survival of tumor cells. This study was conducted to analyze the associations of SLC7 family gene expression with mortality in papillary thyroid carcinoma (PTC). METHODS: Clinical features, somatic mutations, and SLC7 family gene expression data were downloaded from The Cancer Genome Atlas database. Linear regression model analysis was performed to analyze the correlations between SLC7 family gene expression and clinicopathologic features. Kaplan-Meier survival and logistic regression analyses were performed to characterize the associations between gene expression and patients' overall survival. RESULTS: Patient mortality was negatively associated with age and tumor size but positively increased cancer stage and absence of thyroiditis in PTC patients. Kaplan-Meier survival analysis indicated that patients with high SLC7A3, SLC7A5, and SLC7A11 expression levels exhibited poorer survival than those with low SLC7A3, SLC7A5, and SLC7A11 expression levels (P < 0.05 for all cases). Logistic regression analysis showed that SLC7A3, SLC7A5, and SLC7A11 were associated with increased mortality (odds ratio [OR] 8.61, 95% confidence interval [CI] 2.3-55.91; OR 3.87, 95% CI 1.18-17.31; and OR 3.87, 95% CI 1.18-17.31, respectively. CONCLUSION: Upregulation of SLC7A3, SLC7A5, and SLC7A11 expression was associated with poor prognosis in PTC patients, and SLC7 gene expression levels are potentially useful prognostic biomarkers.

Programmed Death-Ligand 1 Expression in Papillary Thyroid Cancer and Its Correlation with Clinicopathologic Factors and Recurrence.

BACKGROUND: Programmed death-ligand 1 (PD-L1) expression has been reported in several malignancies, but the expression of PD-L1 in papillary thyroid cancer (PTC) has been characterized rarely. The aim of this study was to assess the significance of PD-L1 expression and its associations with clinicopathologic factors and disease outcome in PTC. METHODS: Immunohistochemistry staining was conducted retrospectively to evaluate the expression of PD-L1 in a total of 260 PTC tumors and corresponding non-tumor tissues. The correlations between PD-L1 expressions with clinicopathologic features and recurrence-free survival (RFS) were analyzed. RESULTS: PD-L1 expression was positive in 52.3% (136/260) of PTC tumor tissues, which was significantly higher than in corresponding non-tumor thyroid tissues. In clinicopathologic analyses, this positive staining of PD-L1 was positively linked to multifocality (p = 0.001) and extrathyroidal extension (p = 0.001). In multivariate Cox regression analysis, positive PD-L1 expression in tumor tissue was significantly associated with worse RFS (hazard ratio 2.825 [confidence interval 1.149-6.943], p = 0.024). In subgroup analyses based on clinicopathologic factors, positive PD-L1 staining of tumor tissue was associated with worse RFS in males (p = 0.001), older patients (≥45 years; p = 0.001), and patients with a primary tumor size >4 cm (p = 0.002), multifocal tumors (p = 0.031), extrathyroidal extension (p = 0.012), and lymph node metastasis (p = 0.004). In contrast, positive PD-L1 staining predicted worse RFS in the subgroup of patients without Hashimoto's thyroiditis (p = 0.001) and treated with total thyroidectomy (p = 0.019). CONCLUSIONS: PD-L1 is important in determining aggressiveness of PTC and could predict the prognosis of patients. Therefore, inhibition of PD-L1 is suggested as a potential strategy for the treatment of advanced PTC with high expression of PD-L1.

Prognostic significance and optimal cutoff of age in medullary thyroid cancer.

Age has been found to correlate with the prognosis for medullary thyroid cancer (MTC). This study was conducted to investigate whether age can predict long-term unfavorable prognosis and evaluate its predictive accuracy associated with TNM staging, using data of patients diagnosed with MTC between 2000 and 2010 from Surveillance, Epidemiology and End Results database. The relationship between the patients' age at diagnosis and cancer-specific survival (CSS) was evaluated using multivariate Cox regression analysis. Age stratifications were combined into a nomogram model to predict the CSS of MTC. The X-tile program determined 49 and 69 as optimal age cutoff values for CSS. On multivariate analysis, independent factors for survival were age (50-69 years, HR 2.853, 95% CI 1.631-4.991; ≥70 years, HR 5.804, 95% CI 2.91-11.555), race (white, HR 0.344, 95% CI 0.188-0.630), T (T3/4, HR 3.931, 95% CI 2.093-7.381), N (N1a, HR 3.269, 95% CI 1.386-7.710) and M (M1, HR 3.998, 95% CI 2.419-6.606). The C-index for CSS prediction with TNM, age (cutoff of 45)/sex/race/TNM and age (cutoff of 49 and 69)/sex/race/TNM were 0.832 (95% CI 0.763-0.901), 0.863 (95% CI 0.799-0.928), and 0.876 (95% CI 0.817-0.935), respectively. Subgroup multivariate analyses also showed that age significantly increased the risk for CSS in females, non-Hispanic white patients, and those with stage IV MTC. In conclusion, CSS was independently associated with ages between 49 and 69 years, which might be applied for risk stratification in MTC patients.