Purpose Medulloblastomas are heterogeneous and include relatively good-prognosis tumors characterized by Wnt pathway activation, as well as those that cannot be successfully treated with conventional therapy. Developing a practical therapeutic stratification that allows accurate identification of disease risk offers the potential to individualize adjuvant therapy and to minimize long-term adverse effects in a subgroup of survivors. Methods Using formalin-fixed paraffin-embedded (FFPE) tissue for immunohistochemistry, fluorescent in situ hybridization, and direct sequencing to identify tumors with a Wnt pathway signature and those harboring copy number abnormalities (CNAs) of potential prognostic significance (MYC/MYCN amplification, CNAs of chromosome 6 and 17), we evaluated clinical, pathologic, and molecular outcome indicators and stratification models in a cohort (n = 207) of patients with medulloblastoma 3 to 16 years of age from the International Society of Pediatric Oncology CNS9102 (PNET3) trial. Results Metastatic disease and large-cell/anaplastic (LC/A) phenotype were the clinicopathologic variables associated with poor progression-free survival (PFS). Nuclear immunoreactivity for β-catenin, CTNNB1 mutation, and monosomy 6 all identified a group of good-prognosis patients. MYC amplification was associated with poor outcome, but other CNAs were not. Low-risk medulloblastomas were defined as β-catenin nucleopositive tumors without metastasis at presentation, LC/A phenotype, or MYC amplification. High-risk medulloblastomas were defined as tumors with metastatic disease, LC/A phenotype, or MYC amplification. Low-risk, standard-risk, and high-risk categories of medulloblastoma had significantly (P < .0001) different outcomes. Conclusion Integrating assays of molecular biomarkers undertaken on routinely collected diagnostic FFPE tissue into stratification schemes for medulloblastoma alongside clinical and pathologic outcome indicators can refine current definition of disease risk and guide adjuvant therapy.

The long non-coding RNA MEG3 has been reported to be a tumor suppressor in a number of malignant tumors including gastric cancer. Several studies have shown that the regulation of MEG3 may attribute to the promoter hypermethylation. However, the mechanism of MEG3 regulation in gastric cancer is still not well understood. MiR-148a can suppress gastric tumorigenesis through regulating the expression of target genes such as DNA methyltransferase 1(DNMT-1). We examined the expression of MEG3 in 52 gastric cancer samples using quantitative real-time PCR and found the down-regulation of MEG3 in both gastric cancer tissues and cell lines. The positive correlation of MEG3 and miR-148a was further confirmed in SGC-7901 and BGC-823 gastric cancer cell lines. Hypermethylation of MEG3 differentially methylated regions was identified by methylation-specific PCR, and MEG3 expression was increased with the inhibition of methylation with siRNA to DNMT-1 in gastric cancer cells. In addition, transfection of MEG3 siRNA into gastric cancer cells diminished the suppression of proliferation induced by overexpression of miR-148a. Our results suggest that the suppression of miR-148a may contribute to the down-regulation of MEG3 in gastric cancer by modulation of DNMT-1.

Trop2 is considered to have an important function in tumor metastasis and the promotion of epithelial‑mesenchymal transition (EMT). E‑cadherin is a crucial factor in intercellular adhesion and EMT transformation. In the present study, we detected the expression of Trop2 and E‑cadherin in breast cancer (BC) to better define their prognostic value. The mRNA expression levels of these two genes in 20 cases of fresh BC tissues were detected by quantitative real‑time polymerase chain reaction (qRT‑PCR). We also detected the expression levels of these two genes by immunohistochemistry (IHC) in 312 BC tissues, and the correlations between the expression of these two genes and the clinicopathological characteristics in BC patients were analyzed. The mRNA and protein expression levels of the two genes in BC cell lines were studied by qRT‑PCR and western blotting. The results indicated that Trop2+/E‑cadherin‑ was expressed in BC tissues more than that in the matched adjacent tissues. The protein expression results obtained via IHC were similar to the mRNA expression results. Trop2+/E‑cadherin‑ that was expressed in BC was associated with lymph node status, metastasis, tumor‑node‑metastasis (TNM) stage, and ER‑/PR‑/HER2‑ expression. BC patients that expressed Trop2+/E‑cadherin‑ had poor overall survival rates. The results of Trop2 and E‑cadherin expression levels obtained in the BC cell lines were the same as those obtained in the BC tissues. Overall, Trop2 has a potential role in the promotion of EMT in BC and it could be considered as a therapeutic target in the future.