IntroductionCurrently in papillary thyroid cancer (PTC), the correlation between lymph node positivity (LN+) and patient’s age at diagnosis is still inconclusive. The aim of this study was to investigate whether younger PTC patients had higher LN+ rates.Patients and methodsFrom the 1998–2013 Surveillance, Epidemiology, and End Results database, we analyzed PTC patients with at least 1 LN examined. The patients were divided into 5 groups by age separately for each T stage: ≤30; 31–40; 41–50; 51–60; >60 years.ResultsA total of 46,077 PTC patients were identified, including 8,386 (18.2%) patients aged ≤30 years, 10,971 (23.8%) patients aged 31–40 years, 11,646 (25.3%) patients aged 41–50 years, 8,596 (18.7%) patients aged 51–60 years, and 6,478 (14.1%) patients aged >60 years. In each T stage, LN+ rates were inversely associated with age at diagnosis, which was validated by multivariate logistic regression analysis (p<0.001). In addition, the subset of patients 30 or younger had the highest lymph node ratio compared with other subsets (p<0.001).ConclusionWe identified that younger PTC patients have an increased predisposition for LN+ regardless of T stage. This finding could help surgeons to select the optimal treatment for younger PTC patients.

ObjectiveThis study was to evaluate the risk factors of survival in patients with columnar cell variant (CCV) and encapsulated variant (ECV).Materials and methodsThe Surveillance, Epidemiology, and End Results database (1988–2013) was used to compare the characteristics of CCV and ECV with those of classic papillary thyroid carcinoma (PTC). Survival was analyzed by the Kaplan–Meier method, the log-rank test, and Cox multivariate regression. Multivariate logistic regression was used to further analyze lymph node metastases and distant metastasis. There were 765 CCV, 529 ECV, and 39,035 PTC patients. ECV tumors were similar to PTC in terms of overall survival, disease-specific survival, age, sex, and distant metastasis.ResultsCompared with PTC, CCV tumors tended to be larger, with a higher incidence rate among males and in patients ≥65 years of age. CCV was associated with higher rates of extrathyroidal extension, multifocality, lymph node examinations, and lymph node and distant metastases (p<0.0001). Significant differences were found in 10-year overall survival (97.14% vs 89.15%, p<0.0001) and disease-specific survival (99.08% vs 93.07%, p<0.0001) between PTC and CCV. In CCV, distant metastasis (hazard ratio 5.125, p<0.0001) and lymph nodal metastasis (hazard ratio 2.152, p=0.032) predicted a poor prognosis. After adjustment, distant metastasis was independently associated with age ≥65 years, and lymph nodal metastasis was independently associated with female sex (odds ratio [OR] 0.341 [0.234–0.496]), extrathyroidal extension (OR 2.453 [1.368–4.397]), multifocality (OR 2.168 [1.318–3.569]), size >20 mm, ≤40 mm (OR 1.851 [1.170–2.928]), and size >40 mm (OR 1.847 [1.088–3.136]).ConclusionECV appears to have a similar prognosis to PTC, while CCV has a worse prognosis than classic PTC. Treatment with external beam radiotherapy and radioactive implants should be conducted carefully in patients with CCV.

Primary brain tumors are a rare occurrence in comparison to other malignancies, the most predominant form being glioma. Commonly, exposure to ionizing radiations and inheritance of associated conditions such a neurofibromatosis and tuberous sclerosis are the most common causes of development of glioma. However, understanding of the molecular mechanisms that drive glioma development is limited. We explore the role of aberration of microRNA namely miR-494-3p through long noncoding RNA WT1-AS in the development of gliomas. In this study, we found that, levels of WT1-AS were significantly reduced in glioma tissues and cell lines. The miR-494-3p levels were negatively correlated with WT1-AS levels. The cellular proliferation and invasiveness decreased in WT1-AS transfected cell lines. Further the half maximal inhibitory concentration (IC50) of chemotherapeutic agent temozolomide was significantly reduced in the presence of WT1-AS. The cotransfection of WT1-AS and miR-494-3p reduced activation of phospho-AKT (p-AKT). Expression of miR-494-3p is modulated by binding to long noncoding RNA WT1-AS. Deregulation of WT1-AS leads to aberrant expression of miR-494-3p leading to hyperactivation of AKT. This malformation may result in altering protective immune responses in malignancies. Targeting of WT1-AS, miR-494-3p, and AKT may be novel therapeutic options in treatment of glioma.

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Hepatocellular carcinoma (HCC) is the most frequently diagnosed primary liver cancer with a high mortality rate and imposes a huge burden on patients and society. Recently, ubiquitin-specific protease 35 (USP35) was found to be involved in cell proliferation and mitosis, but its role in HCC remains largely unknown. The expression of USP35 in HCC and its association with patient prognosis in the study cohort and public databases was analyzed in the present study. The effects of USP35 on the malignant biological behavior of HCC were analyzed by cellular functional experiments. Mechanistically, the effect of USP35 deubiquitylation on the M2 splice isoform of pyruvate kinase (PKM2) and on the Warburg effect of tumor cells were verified by western blotting and ubiquitination assay. The results of the present study demonstrated that USP35 is highly expressed in HCC and its high expression is significantly associated with poor prognosis of patients with HCC. In the present study, it was also demonstrated that inhibiting the expression of USP35 can impair the malignant properties (proliferation, migration and invasion) of HCC tumor cells by elevating the ubiquitination level of PKM2, the deubiquitinated form of which is critical for glycolysis in tumor cells. The present study therefore indicated that USP35 may be a target in the treatment of HCC.