RESUMO
Long non-coding RNAs (lncRNAs) are key regulators of a range of human diseases, including various cancers, with multiple previous studies having explored lncRNA dysregulation in the context of gastric cancer (GC). The present study sought to expand upon these previous results by downloading lncRNA, mRNA, and microRNA (miRNA) expression profiles derived from 180 GC tissues and 24 normal control tissues within the Cancer Genome Atlas (TCGA) database. These datasets were then interrogated to identify GC-related differentially expressed (DE) RNAs (|fold change| ≥ 2, FDR< 0.01), leading to the identification of 1946 DE lncRNAs, 123 DE miRNAs, and 3159 DE mRNAs. These results were then used to generate a putative GC-related competitive endogenous RNA (ceRNA) network composed of 131 lncRNAs, 9 miRNAs, and 78 mRNAs. Subsequent survival analyses based upon this network revealed 17 of these lncRNAs to be significantly associated with GC patient survival (P < 0.05). Further multivariable Cox regression and lasso analyses allowed for the construction of an 8-lncRNA risk score that was able to effectively predict GC patient survival with good discriminative ability. The Kaplan-Meier Plotter database further confirmed that network hub genes that were related to these 8 lncRNAs were associated with GC patient prognosis (P < 0.05). As the ceRNA network in the present study was constructed with a focus on both disease stage and differential gene expression, it represents a key resource that will offer valuable insights into the mechanistic roles of ceRNA pathways in GC development and progression.
RESUMO
Preoperative prognostic nutritional index (PNI) has been widely used for the clinical evaluation of patients with cancer. The present study assessed the prognostic value of preoperative PNI in patients after gastric cancer (GC) radical surgery. The clinical case and follow-up data of 170 patients undergoing GC radical surgery were retrospectively analyzed. The receiver operating characteristic (ROC) curve was used to compare the predictive ability of each inflammatory index: The PNI, neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR). The correlation between the preoperative PNI and overall survival (OS) was also analyzed via Kaplan-Meier (K-M) curves and multivariate Cox regression analyses. The results revealed that the optimal PNI cut-off was 46.030. According to this cut-off value, the whole sample was divided into PNI <46.030 (low PNI group) and PNI ≥46.030 (high PNI group). These groups were comprised of 102 and 68 cases, respectively. The area under the curve value of the PNI was 0.725, which was greater than that of traditional inflammatory indices, including the NLR and LMR. K-M survival analysis revealed that the 5 year survival rate of patients in the low PNI group was significantly lower than that of patients in the high PNI group (P<0.01). Univariate analysis and Cox multiple regression model analysis demonstrated that the T stage, N stage, pathological grade and PNI were independent risk factors for the 5 year survival rate after radical gastrectomy (P<0.05). In conclusion, the preoperative PNI is an independent risk factor for 5 year survival after radical gastrectomy and has clinical value for the prognostic evaluation of patients with GC.
RESUMO
Long non-coding RNAs (lncRNAs) have been shown to play important roles in many human diseases. However, their functions and mechanisms in tumorigenesis and development remain largely unknown. Here, we demonstrated that focally amplified lncRNA in epithelial cancer (FALEC) was upregulated and significantly correlated with lymph node metastasis, TNM stage in gastric cancer (GC). Further experiments revealed that FALEC knockdown significantly inhibited GC cells migration and invasion in vitro. Mechanistic investigations demonstrated that small interfering RNA-induced silencing of FALEC decreased expression of the nearby gene extracellular matrix protein 1 (ECM1) in cis. Additionally, ECM1 and FALEC expression were positively correlated, and high levels of ECM1 predicted shorter survival time in GC patients. Our results suggest that the downregulation of FALEC significantly inhibited the migration and invasion of GC cells through impairing ECM1 expression by exerting an enhancer-like function. Our work provides valuable information and a novel promising target for developing new therapeutic strategies in GC.
RESUMO
OBJECTIVE: To investigate the differentially expressed genes between gastric cancer and normal gastric mucosa by bioinformatics analysis, identify the important gene participating in the occurrence and progression of gastric cancer, and predict the functions of these genes. METHODS: The gene expression microarray data GSE100935 (including 18 gastric cancer samples and normal gastric mucosal tissues) downloaded from the GEO expression profile database were analyzed using Morpheus to obtain the differentially expressed genes in gastric cancer, and a cluster analysis heat map was constructed. The online database UALCAN was used to obtain the expression levels of these differentially expressed genes in gastric cancer and normal gastric mucosa. The prognostic value of the differentially expressed genes in gastric cancer was evaluated with Kaplan-Meier survival analysis. GO functional enrichment analysis was performed using Fun-Rich software, and the STRING database was exploited to establish a PPI network for the differentially expressed genes. RESULTS: A total of 45119 differentially expressed genes were identified from GSE100935 microarray data. Analysis with UALCAN showed an obvious high expression of EXD3 gene in gastric cancer, and survival analysis suggested that a high expression level of EXD3 was associated with a poorer prognosis of the patients with gastric cancer. GO functional enrichment analysis found that the differentially expressed genes in gastric cancer were involved mainly in the regulation of nucleotide metabolism and the activity of transcription factors in the cancer cells. CONCLUSIONS: EXD3 may be a potential oncogene in gastric cancer possibly in relation to DNA damage repair. The up-regulation of EXD3 plays an important role in the development and prognosis of gastric cancer, and may serve as an important indicator for prognostic evaluation of the patients.