Glycosylation has significant effects on cancer progression. Fucosylation is one of the most important glycosylation events involved in hepatocellular carcinoma (HCC). Here, we compared N-glycan profiles of liver tumor tissues and adjacent tissues of 27 HCC patients to reveal the association between fucosylation and HCC progression, as well as verified the potential role of miRNA in regulating fucosylation. Mass spectrometry (MS) analysis showed pronounced differences of the N-glycosylation patterns and fucosylated N-glycans between the adjacent and tumor tissues. Different fucosyltransferase (FUT) genes were also identified in adjacent and tumor tissues, and two HCC cell lines with different metastatic potential. High-level expression of FUT8 was detected in tumor tissues and highly metastatic HCC cells. Altered levels of FUT8 in HCC cell lines significantly linked to the malignant behaviors of proliferation and invasion in vitro. Furthermore, using microRNA array, we identified FUT8 as one of the miR-26a, miR-34a and miR-146a-targeted genes. An inverse correlation was revealed between the expression levels of FUT8 and these miRNAs. Luciferase reporter assay demonstrated these miRNAs specifically interacted with the 3′UTR of FUT8 and subsequently down-regulated FUT8 expression-level. The forced expression of these miRNAs was able to induce a decrease in FUT8 levels and thereby to suppress HCC cells progression. Altogether, our results indicate that fucosylated N-glycan and FUT8 levels can be used as markers for evaluating HCC progression, as well as miRNAs may be involved in inhibition of fucosylation machinery through targeting FUT8.
DNA methylation at the 5 position of cytosine (5-mC) is an epigenetic hallmark that is critical in various biological and pathological processes such as DNA methylation regulation, and initiation and development of cancers. 5-mC can be oxidized to 5-hydroxymethylcytosine (5-hmC) by the ten-eleven translocation family of DNA hydroxylases. Accumulating evidence has reported that loss of 5-hmC is associated with cancer development. However, its level in papillary thyroid carcinoma (PTC) remains unclear. The present study reports that the loss of 5-hmC is an epigenetic mark of PTCs, associated with their malignant biological behavior, providing diagnostic and predictive advantages over DNA hypomethylation (5-mC), an acknowledged epigenetic alteration in cancer. In addition, the 5-hmC staining levels were decreased in cases of micro-carcinoma with lymph node metastasis, which suggests that 5-hmC expression levels could be used as valuable biomarkers for predicting malignant potential and assist in the selection of therapeutic strategies in PTC; therefore, 5-hmC has the potential to provide a more precise direction for PTC therapy.
Upregulation of the epithelial cell adhesion molecule (EpCAM) is involved in tumor progression. Cyclooxygenase (COX)‑2 is the key enzyme catalyzing prostaglandin synthesis and is involved in breast cancer progression and metastasis. However, the prognostic value of EpCAM and its putative correlation with COX‑2 in breast cancer have yet to be elucidated. The aim of the present study was to assess the clinical relevance of the relationship between EpCAM and COX‑2, via examining the putative correlation between EpCAM and COX‑2 expression in various types of human breast cancer. A total of 134 breast cancer tissue samples was examined in the present study. Immunohistochemistry approach was used to detect EpCAM and COX‑2 expression in the tissue microarrays. Spearman's correlation analysis was performed to evaluate the correlation between the protein expression and clinicopathological parameters present in patients with various tumor subtypes, with the aim to potentially establish a relationship between EpCAM/COX‑2 and clinical prognosis. Expression of EpCAM and COX‑2 was revealed to be associated with tumor progression, and poor prognosis in breast cancer. The present findings demonstrated that EpCAM was involved in the regulation of COX‑2 expression, and a positive correlation between the proteins was associated with poor prognosis in patients with breast cancer. The present results suggest that EpCAM and COX‑2 may have potential as prognostic biomarkers in the diagnosis and treatment of patients with breast cancer.
Objectives: To confirm the long-term efficacy and safety of radiofrequency ablation (RFA) for low-risk papillary thyroid microcarcinoma (PTMC). Methods: We retrospectively reviewed data of 102 primary papillary thyroid carcinoma patients (82 women, 20 men; mean age: 43 [19] years) treated with radiofrequency ablation and thyroid-stimulating hormone (TSH) suppression therapy before December 2018. All patients were at high surgical risk or refused surgery. They were followed up at 1, 3, 6, 9, and 12 months and every 6-12 months thereafter using ultrasound and contrast-enhanced ultrasound. The volume and volume reduction ratio was calculated. Recurrence and lymph node or distant metastasis were evaluated. Results: The mean initial tumor diameter was 0.50 (0.29) cm; the mean initial volume was 0.06 (0.09) mL. At 1, 3, 6, 9, 12, 24, 36, 48, and 60 months after RFA, complete resorption rates were 0, 0, 9.8 (10/ 102), 33.3 (34/102), 91.2 (93/102), 96.1 (98/102), 99 (101/102), 100, and 100%, respectively. Two patients had developed ipsilateral neck lymph node metastasis in regions IV and VI at 30-and 18month follow-ups, respectively. After RFA, 3/102 patients (2.9%) developed hoarseness-the main side effect. No life-threatening or delayed complications occurred. The TSH value in the initial period was 0.06 (0.02) mIU/mL; the rate of reaching the TSH target was 85.7%. The TSH value at follow-up was 1.47 (0.91) mIU/mL; the compliance rate was 99.3%. Conclusions: Ultrasound-guided RFA for PTMC is highly effective and safe. RFA can serve as a minimally invasive treatment for PTMC patients who refuse surgery or active surveillance.
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