Key factors mediated by PI3K signaling pathway and related genes in endometrial carcinoma.

By analyzing the gene expression of endometrial carcinoma (EC) patients, the key factors in PI3K signaling pathway and its related genes mediating EC were explored. The EC samples and normal endometrial samples were downloaded from TCGA database and GTEx database. The R language "limma" package was used for differential analysis, and the expression level of genes in each tissue was analyzed by "gganatogram" package. Functional enrichment analysis of differential genes was carried out by KOBAS, an online bioinformatics website. The correlation between key genes and differential genes was evaluated using TCGA data and GTEx combined gene expression data. The corresponding clinical data were downloaded from TCGA database and GTEx database, and the R language "survival" package was used to assess the potential of candidate differential genes as a key factor of EC. Based on the combined differential analysis of TCGA and GTEx databases, 299 genes with significant differential in expression were finally got. Functional enrichment analysis revealed that genes were predominantly enriched in the entry of "Pathways in cancer", including RAC2 and PIK3R3 genes which were related with the abnormal PI3K pathway in cancer. PIK3R3, a key gene in the PI3K signaling pathway, was highly-expressed in EC. SPDEF, GCNT2, KIAA1324, C9orf152, MARVELD3, and APEX2 genes were found to be positively correlated with PIK3R3 in EC, all of which were highly expressed in EC. KM survival analysis showed that SPDEF, GCNT2, KIAA1324 and C9orf152 were significantly correlated with patients' survival. ROC analysis showed that SPDEF, GCNT2, KIAA1324 and C9orf152 gene could be used as potential markers for prognosis and survival of EC patients. It was found that PIK3R3, a key gene in the PI3K signaling pathway, was highly expressed in EC. The SPDEF, GCNT2, KIAA1324 and C9orf152 genes were also highly expressed in EC, and were positively correlated with PIK3R3 in EC. Moreover, they are significantly correlated with the patients' survival, suggesting that they may be potential markers for the prognosis of patients with EC.

RUNX3 Expression Level Is Correlated with the Clinical and Pathological Characteristics in Endometrial Cancer: A Systematic Review and Meta-analysis.

Human Runt-associated transcription factor 3 (RUNX3) plays an important role in the development and progression of endometrial cancer (EC). However, the clinical and pathological significance of RUNX3 in EC needs to be further studied. In order to clarify the clinical and pathological significance of RUNX3, a systematic review and meta-analysis was conducted in EC patients. Keywords RUNX3, endometrial cancer, and uterine cancer were searched in Cochrane Library, Web of Knowledge, PubMed, CBM, MEDLINE, and Chinese CNKI database for data up to Dec 31, 2018. References, abstracts, and meeting proceedings were manually searched in supplementary. Outcomes were various clinical and pathological features. The two reviewers performed the literature searching, data extracting, and method assessing independently. Meta-analysis was performed by RevMan5.3.0. A total of 563 EC patients were enrolled from eight studies. Meta-analysis results showed that the expression of RUNX3 has significant differences in these comparisons: lymph node (LN) metastasis vs. non-LN metastasis (P = 0.26), EC tissues vs. normal tissues (P < 0.00001), clinical stages I/II vs. II/IV (P < 0.00001), muscular infiltration < 1/2 vs. muscular infiltration ≥ 1/2 (P < 0.00001), and G1 vs. G2/G3 (P < 0.00001). The decreasing expression of RUNX3 is associated with poor TNM stage and muscular infiltration. It is indicated that RUNX3 was involved in the suppression effect of EC. However, further multicenter randomized controlled trials are needed considering the small sample size of the included trials.

Proteomic Analysis of Human Endometrial Tissues Reveals the Roles of PI3K/AKT/mTOR Pathway and Tumor Angiogenesis Molecules in the Pathogenesis of Endometrial Cancer.

As one major gynecological malignancy, endometrial cancer (EC) has been widely studied recently. However, its pathogenesis is still unclear to date. In this study, we identified differentially expressed proteins between 30 endometrial cancer tissues and 30 matched normal controls using 2D LC-MS/MS quantitative proteomics. As a result, we identified 619 differentially expressed proteins among all 2521 proteins being quantified. Further analyses suggested that the changes of fat, amino acid metabolism, peroxisome, extracellular signal, cytoskeleton, and other signaling or metabolic pathways may be closely related to the development of this cancer. Particularly, the PI3K/AKT/mTOR pathway-related molecules including PI3K and mTOR, ERK (the molecule of the ERK pathway), SPP1, and ANGPT2 (angiogenesis-related molecules) are highly associated with the pathogenesis of EC, which were reconfirmed by western blot and immunohistochemistry (IHC) analysis. In summary, our study revealed that the PI3K/AKT/mTOR pathway and tumor angiogenesis molecules contribute to the pathogenesis of endometrial cancer.

Wogonin exacerbates the cytotoxic effect of oxaliplatin by inducing nitrosative stress and autophagy in human gastric cancer cells.

BACKGROUND: Gastric cancer remains one of the leading cause of death in the world. Drug combinations are potential approaches to provide more efficient treatments that minimize side effects. PURPOSE: We investigated the pharmacological effects of the combination of wogonin with oxaliplatin on gastric cancer cells in vitro and in vivo. METHODS AND RESULTS: In the present study, we found that wogonin enhanced the cytotoxicity of oxaliplatin; the drug combination resulted in strong synergistic inhibition of the cell viability in BGC-823 cells and in a zebrafish xenograft model. Interestingly, the combined treatment of wogonin and oxaliplatin modulated the expression of phospho-JNK (Thr183/Tyr185), phospho-ULK1 (Ser555) and the formation of LC3II. Confocal imaging data consistently showed that wogonin exacerbates the oxaliplatin-induced dissipation of the mitochondrial membrane potential (ΔΨm) and formation of peroxynitrite in BGC-823 cells. Moreover, wogonin allows a reduction in oxaliplatin dose when they are combined; therefore, it is a relevant strategy for reducing the side effects of oxaliplatin while achieving the same response. CONCLUSION: These results suggest that wogonin can be a potential therapeutic candidate for enhancing the efficacy of oxaliplatin in gastric cancer treatment.