BackgroundThe influences of oncogenic Ezh2 on the progression and prognosis of gastric cancer (GC) and the underlying mechanisms are still poorly understood. Here, we aimed at investigating clinicopathological significance of Ezh2 in GC and the mechanisms underlying its function in GC development.MethodsThe expression level of Ezh2 was determined by qRT-PCR, immunoblot, and immunohistochemistry analysis in 156 pairs of GC tissues and adjacent normal gastric mucosa tissues. The biological functions of Ezh2 were assessed by in vitro and in vivo functional experiments. Chromatin immunoprecipitation (ChIP), luciferase, and Western blotting analyses were utilized to identify the relationship between Ezh2 and the PTEN/Akt signaling.ResultsThe expression of Ezh2 was higher in gastric cancer tissues in comparison with para-nontumorous epithelium. High expression of Ezh2 was associated with more aggressive biological behavior and poor prognosis in GC. In vitro studies indicated that Ezh2 promoted GC cells’ proliferation and clonogenicity. Besides, Ezh2 led to the acquisition of epithelial–mesenchymal transition (EMT) phenotype of GC cells and enhanced GC cell migration and invasion capacity. In particular, Ezh2 strengthened sphere-forming capacity of GC cells, indicating its role in the enrichment of GC stem cells. Furthermore, we found that PTEN/Akt signaling contributed to the effects of Ezh2 on cancer stem cells (CSC) and EMT phenotype in GC cells, and blocking PTEN signaling significantly rescued the effects of Ezh2.ConclusionsTaken together, Ezh2 has a central role in regulating diverse aspects of the pathogenesis of GC in part by involving PTEN/Akt signaling, indicating that it could be an independent prognostic factor and potential therapeutic target.Electronic supplementary materialThe online version of this article (10.1186/s13045-017-0547-3) contains supplementary material, which is available to authorized users.
Tumor microenvironment (TME) has been illustrated their clinic pathological significance in predicting outcomes and therapeutic efficacy by more and more studies. Tumor purity, which reflects the features of TME, is defined as the proportion of cancer cell in the tumor tissue. However, the current staging and prognostic prediction system in gastric cancer (GC) paid little attention to TME. Therefore, we carried out the study to explore the role of tumor purity in GC. We retrospectively collected the clinical and transcriptomic data from four public data sets (n = 1340),
GSE15459
,
GSE26253
,
GSE62254
, and The Cancer Genome Atlas (TCGA). About 34 GC patients from Fudan University Shanghai Cancer Center (FUSCC) were assigned as an independent validation group. Tumor purity was measured by a computational method. Low tumor purity was associated with unfavorable prognosis, upregulated EMT and stemness pathways, more infiltrating of Tregs, M1 and M2 macrophages and a higher expression level of various immune checkpoints and chemokines recruiting immune suppressive cells. Our study indicates low tumor purity in GC was associated with unfavorable prognosis and immune‐evasion phenotype. Further investigations toward tumor purity in GC may contribute to prognosis prediction and the decision of therapy strategies.
Liver metastasis from breast cancer has poor prognosis. We aimed at developing a reliable tool for making a distinction and prediction for liver metastasis in breast cancer patients, thus helping clinical diagnosis and treatment. In this study, totally 6238 patients from SEER database with known distant metastasis status and clinicopathologic variables were enrolled and divided randomly into training and validating groups. Logistic regression was used to screen variables and a nomogram was constructed. After multivariate logistic regression, sex, histology type, N stage, grade, age, ER, PR, HER2 status as significant variables for constructing the nomogram. The nomogram for distinguishing and predicting liver metastasis in breast cancer passed the calibration and validation steps and the areas under the receiver operating characteristic curve of the training set and the validation set were 0.6602 and 0.6511 respectively. Our nomogram is a reliable and robust tool for the distinction and prediction of liver metastasis in breast cancer patients, thus helping better choose medical examinations and optimize therapeutic regimen under the cooperation among medical oncologists and surgeons.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.