E2F1 Maintains Gastric Cancer Stemness Properties by Regulating Stemness-Associated Genes

Purpose. To determine the regulatory role of E2F1 in maintaining gastric cancer stemness properties and the clinical significance of E2F1 in gastric cancer. Materials and Methods. We conducted a tumor spheroid formation assay to enrich gastric cancer stem-like cells. The protein and mRNA expression levels of genes were measured using Western Blot and qRT-PCR. Lentivirus-mediated overexpression and downregulation of E2F1 were performed to evaluate the effect of E2F1 on the stemness properties of gastric cancer cells. The effect of E2F1 on gastric cancer cell sensitivity of 5-Fu was evaluated using cell viability assay and TdT-mediated dUTP Nick-End Labeling staining. We also analyzed the association between E2F1 expression and clinical characteristics in gastric cancer patients. The KM plotter database was used to analyze the relationship between E2F1 and overall survival in GC patients. Results. We found that E2F1 expression was significantly higher in gastric cancer tissues than in the paired adjacent normal tissues (p<0.05) and was positively correlated with tumor size (p<0.05), T stage (p<0.05), and differentiation degree (p<0.05). KM plotter database demonstrated a close association between higher E2F1 expression level and worse overall survival of gastric cancer patients (p<0.05). In vitro assay illustrated that E2F1 could regulate the expression of stemness-associated genes, such as BMI1, OCT4, Nanog, and CD44, and maintain the tumor spheroid formation ability of gastric cancer cells. E2F1 enhanced 5-Fu resistance in gastric cancer cells, and the E2F1 expression level was correlated with the prognosis of gastric cancer patients receiving 5-Fu therapy. The expression levels of stemness-associated genes were also significantly higher in gastric cancer tissues than the paired adjacent normal tissues (p<0.05). A positive correlation was observed between E2F1 and BMI1 (r = 0.422, p<0.05), CD44 (r = 0.634, p<0.05), OCT4 (r = 0.456, p<0.05), and Nanog (r = 0.337, p<0.05) in gastric cancer tissues. The co-overexpression of E2F1 and stemness-associated genes was associated with worse overall survival. Conclusion. E2F1 plays a significant role in gastric cancer progression by maintaining gastric cancer stemness properties through the regulation of stemness-associated genes. The close association between E2F1 and poor prognosis of patients suggests that E2F1 could serve as a prognostic biomarker and a therapeutic target in gastric cancer patients

Low versus high radioiodine activity to ablate the thyroid after thyroidectomy for cancer: a meta-analysis of randomized controlled trials (vol 48, pg 96, 2015)

Endocrinology &amp; MetabolismSCI(E)[email protected]

LncRNA PVT1 Mediates Antiapoptosis and 5-Fluorouracil Resistance via Increasing Bcl2 Expression in Gastric Cancer

Purpose. Plasmacytoma variant translocation 1 (PVT1) is a long noncoding RNA encoded by the human PVT1 gene, which has been verified to mediate tumorigenesis in gastric cancer. However, the underlying molecular mechanisms of PVT1 in gastric cancer (GC) remain largely unknown. Methods. The tumorigenic ability of PVT1 was verified by subcutaneous and orthotopic mouse models. Flow cytometry assay and TdT-mediated dUTP Nick-End Labeling staining were conducted to explore the effects of PVT1 on gastric cancer cell apoptosis. We investigated the relative gene and protein that are involved in apoptosis in real-time PCR and western blot assay. The resistance to 5- Fluorouracil (5-Fu) caused by PVT1 was evaluated using cell viability assay. Then, to confirm the effects of PVT1 on 5-Fu resistance, we conducted the Kaplan-Meier analysis based on three public databases. Results. We confirmed that PVT1 can promote the progression of gastric cancer. PVT1 inhibited the apoptosis of GC cells, which may account for its promotion on GC. We confirmed that PVT1 can regulate the expression of Bcl2 and enhance drug-resistance of gastric cancer to 5-Fu. Kaplan-Meier analysis showed that patients with high PVT1 expression do not experience survival related benefits from 5-Fu based chemotherapy; instead, therapy containing no 5-Fu chemotherapy can improve the first progression survival and overall survival of high PVT1 expression GC patients significantly. Conclusion. Our results showed that PVT1 can inhibit the apoptosis and enhance the 5-Fu resistance of gastric cancer through the activation of Bcl2. PVT1 has the potential to serve as an indicator to predict 5-Fu treatment resistance

DataSheet_3_The value of metabolic LncRNAs in predicting prognosis and immunotherapy efficacy of gastric cancer.docx

IntroductionAs a unique feature of malignant tumors, abnormal metabolism can regulate the immune microenvironment of tumors. However, the role of metabolic lncRNAs in predicting the prognosis and immunotherapy of gastric cancer (GC) has not been explored.MethodsWe downloaded the metabolism-related genes from the GSEA website and identified the metabolic lncRNAs. Co-expression analysis and Lasso Cox regression analysis were utilized to construct the risk model. To value the reliability and sensitivity of the model, Kaplan–Meier analysis and receiver operating characteristic curves were applied. The immune checkpoints, immune cell infiltration and tumor mutation burden of low- and high-risk groups were compared. Tumor Immune Dysfunction and Exclusion (TIDE) score was conducted to evaluate the response of GC patients to immunotherapy.ResultsTwenty-three metabolic lncRNAs related to the prognosis of GC were obtained. Three cluster patterns based on metabolic lncRNAs could distinguish GC patients with different overall survival time (OS) effectively (pDiscussionThe metabolic lncRNAs risk model can reliably and independently predict the prognosis of GC. The feature that simultaneously map the immune status of tumor microenvironment and TMB gives risk model great potential to serve as an indicator of immunotherapy.</p