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Accumulating evidence has demonstrated that circular RNAs (circRNAs) play vital roles in cancer progression. However, the underlying molecular mechanisms of circRNAs remain poorly elucidated in gastric cancer (GC). The main purpose of present study is to explore the underlying regulatory mechanism by constructing a circRNA-associated competitive endogenous RNA (ceRNA) network and further establish a robust prognostic signature for patients with GC. Based on expression data of circRNA, microRNA, and mRNA derived from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases, a circRNA-associated ceRNA network, containing 15 cirRNAs, 9 microRNAs, and 35 mRNAs, was constructed using the Starbase database. Functional enrichment analysis showed that the ceRNA network might be involved in many cancer-related pathways, such as regulation of transcription from RNA polymerase II promoter, mesodermal cell differentiation, and focal adhesion. A protein-protein interaction network was constructed based on genes within the circRNA-associated ceRNA network. We found that six of ten hub genes within the PPI network were significantly associated with overall survival (OS). Thus, using the LASSO method, we constructed a three-gene prognostic signature based on TCGA-GC cohort, which could classify GC patients into low-risk and high-risk groups with significant difference in OS (HR = 1.9, 95%CI = 1.14-3.2, and log-rank p = 0.001). The prognostic performance of the three-gene signature was verified in GSE15459 (HR = 1.9, 95%CI = 1.27-3.0, and log - rank p = 2.2E - 05) and GSE84437 (HR = 1.5, 95%CI = 1.17-2.0, and log - rank p = 6.3E - 04). Multivariate Cox analysis further revealed that the three-gene prognostic signature could serve as an independent risk factor for OS. Taken together, our findings contribute to a better understanding of the underlying mechanisms of circRNAs in GC progression. Furthermore, a robust prognostic signature is meaningful to facilitate individualized treatment for patients with GC.
Background. Vasculogenic mimicry can promote tumor growth and metastasis. This article is aimed at conducting a systematic meta-analysis to explore the clinicopathological and prognostic significance of vasculogenic mimicry and gastric cancer. Methods. We searched Pubmed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, and the VIP and Wanfang Database for eligible studies. We manually searched for printed journals and relevant textbooks. Subgroups analyses were performed based on the region, manuscript quality, methods of vasculogenic mimicry identification, pathology, and number of patients. Results. Nine studies with 997 patients were included in this meta-analysis. A significant association was observed between vasculogenic mimicry-positive patients and those with gastric cancer with poor overall survival (hazard ratio = 2.24, 95% confidence interval: 1.45-3.47), poor pathological grading, high tumor node metastasis clinical stage, lymph node metastasis, deep tumor invasion, and distant metastasis. Conclusions. Vasculogenic mimicry is associated with a poor prognosis in patients with gastric cancer in China. Clinical studies with large samples are needed worldwide and standardized protocols should be adopted in the future to achieve a better understanding of the relationship between gastric cancer and vasculogenic mimicry.
Previous studies have examined the associations of DNA methyltransferase 1 (DNMT1) polymorphisms, including single nucleotide polymorphisms rs16999593 (T/C), rs2228611 (G/A), and rs2228612 (A/G), with cancer risk. However, the results are inconclusive. The aim of this meta-analysis is to elucidate the associations between DNMT1 polymorphisms and cancer susceptibility. The PubMed, Embase, Web of Science, and Chinese National Knowledge Infrastructure databases were searched systematically to identify potentially eligible reports. Odd ratios and 95% confidence intervals were used to evaluate the strength of association between three DNMT1 polymorphisms and cancer risk. A total of 16 studies were finally included in the meta-analysis, namely, nine studies of 3378 cases and 4244 controls for rs16999593, 11 studies of 3643 cases and 3866 controls for rs2228611, and three studies of 1343 cases and 1309 controls for rs2228612. The DNMT1 rs2228612 (A/G) polymorphism was significantly related to cancer risk in the recessive model. The meta-analysis also suggested that DNMT1 rs16999593 (T/C) may be associated with gastric cancer, while rs2228611 (G/A) may be associated with breast cancer. In future research, large-scale and well-designed studies are required to verify these findings.
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