Correlation of mir-221-3p differential expression with clinical characteristics of gastric cancer patients.

BACKGROUND: Gastric cancer (GC) is one of the most common digestive malignancies. Although miR-221-3p was defined as a novel biomarker in many types of cancer, the relationship between its expression differences and the clinicopathological characteristics and prognosis of GC patients was yet to be fully understood. METHODS AND RESULTS: TCGA database was utilized to predict the potential biological function of miR-221-3p in GC. QRT-PCR and RNA FISH were performed to detect the expression levels of miR-221-3p in GC. The miR-221-3p expression levels in GC tissues and cells were significantly higher than those in paracancerous tissues (p < 0.001) and normal gastric mucosal cells (p < 0.05). Higher expression levels of miR-221-3p were associated with tumor diameter ≥ 4 cm (χ2 = 5.519, p = 0.019), cTNM stage (III + IV) (χ2 = 28.013, p = 0.000), lymph node metastasis (χ2 = 23.272, p = 0.000) and distant metastasis (χ2 = 7.930, p = 0.005). Kaplan-Meier survival analysis showed a better prognosis for GC patients with miR-221-3p low expression(HR = 4.520, 95% CI: 1.844-11.075). CONCLUSIONS: miR-221-3p is highly expressed in GC tissues, which plays an important role in tumorigenesis, invasion and metastasis. miR-221-3p may become an important biomarker and potential molecular therapeutic target for patients with GC.

Construction of a Cuproptosis-Related Gene Signature for Predicting Prognosis in Gastric Cancer.

This study aimed to develop and validate a cuproptosis-related gene signature for the prognosis of gastric cancer. The data in TCGA GC TPM format from UCSC were extracted for analysis, and GC samples were randomly divided into training and validation groups. Pearson correlation analysis was used to obtain cuproptosis-related genes co-expressed with 19 Cuproptosis genes. Univariate Cox and Lasso regression analyses were used to obtain cuproptosis-related prognostic genes. Multivariate Cox regression analysis was used to construct the final prognostic risk model. The risk score curve, Kaplan-Meier survival curves, and ROC curve were used to evaluate the predictive ability of Cox risk model. Finally, the functional annotation of the risk model was obtained through enrichment analysis. Then, a six-gene signature was identified in the training cohort and verified among all cohorts using Cox regression analyses and Kaplan-Meier plots, demonstrating its independent prognostic significance for gastric cancer. In addition, ROC analysis confirmed the significant predictive potential of this signature for the prognosis of gastric cancer. Functional enrichment analysis was mainly related to cell-matrix function. Therefore, a new cuproptosis-related six-gene signature (ACLY, FGD6, SERPINE1, SPATA13, RANGAP1, and ADGRE5) was constructed for the prognosis of gastric cancer, allowing for tailored prediction of outcome and the formulation of novel therapeutics for gastric cancer patients.

miR-129-5p suppresses proliferation, migration, and induces apoptosis in pancreatic cancer cells by targeting PBX3.

Pancreatic cancer (PC) is the seventh most frequent cause of cancer-related deaths worldwide with a high mortality. MicroRNAs (miRNAs) act as important regulators for the development of PC and participate in the progression of PC. miR-129-5p was reported to regulate the progression of tumors, such as thyroid cancer and gastric cancer. However, the function of miR-129-5p in PC is still unclear. In this study, the down-regulation of miR-129-5p was detected in PC tissues and PC cells. miR-129-5p was overexpressed or knocked down in AsPC-1 and BxPC-3 cells. The results showed that miR-129-5p overexpression suppressed proliferation, migration and invasion, and induced apoptosis of PC cells, whereas miR-129-5p knockdown showed opposite effects. In addition, we found that pre-B-cell leukemia homeobox 3 (PBX3) overexpression promoted proliferation, migration and invasion, but reduced apoptosis of PC cells. PBX3 was identified as a target of miR-129-5p by informatics analysis and dual luciferase reporter assay. Finally, our results indicated that miR-129-5p suppressed cell proliferation and migration by targeting PBX3. This study demonstrated that miR-129-5p could function as a tumor suppressor in the progression and development of PC by targeting PBX3, providing a reliable prognostic factor and a new therapeutic strategy for PC.

The Effect of Delayed Oncology Surgery on Survival Outcomes for Patients With Gastric Cancer During the COVID-19 Pandemic: Evidence-Based Strategies.

Objective: To evaluate the impact of delay in gastrectomy on gastric cancer patients' survival outcomes during the COVID-19 pandemic. Methods: Databases including PubMed, MEDLINE (using the Ovid platform), Embase, the Cochrane Library, COVID-19 Open Research Dataset Challenge, COVID-19 Research Database (WHO), ClinicalTrials.gov, and WHO International Clinical Trials Registry Platform were searched for studies of any design and in any setting that included patients with gastric cancer from their inception to July 31, 2021. Hazard ratio (HR) and 95% confidence intervals (CI) of research endpoints in each study were calculated. Statistical analyses were performed with Stata 12.0. Results: A total of 8 studies involving 4,052 gastric cancer patients were eligible and included in the present meta-analysis. The result of the meta-analysis was shown that delaying surgery for less than 8 weeks may not decrease OS (HR = 0.91, 95% CI: 0.80~1.04, p = 0.167) and DFS (HR = 0.96, 95% CI: 0.62~1.50, p = 0.872) in gastric cancer. Our meta-analysis also illustrated that delay in surgery for more than 4 weeks (HR = 0.85, 95% CI: 0.56~1.27, p = 0.421), 6 weeks (HR = 0.88, 95% CI: 0.61~1.27, p = 0.490), and 8 weeks (HR = 0.93, 95% CI: 0.80~1.07, p = 0.314) was also not associated with a decreased OS. Conclusion: A delay in surgery of less than 8 weeks is not associated with worse overall survival for patients with gastric cancer.

[Expression of thioredoxin reductase 1 (TrxR1) in gastric cancer and its effect on the growth of gastric cancer cells].

OBJECTIVE: To investigate the relationship between the expression of thioredoxin reductase 1 (TrxR1) in gastric cancer tissues and the survival time of patients with gastric cancer and its effect on the growth of gastric cancer cells. METHODS: The expression level of TrxR1 mRNA in gastric cancer tissues and adjacent tissues of 76 patients was determined by real-time PCR assays, and the relationship between the mRNA expression level of TrxR1 and the clinicopathological characteristics and prognosis of gastric cancer patients was analyzed. Three gastric cancer tissues and adjacent tissues were randomly selected, and the expression of TrxR1 protein was detected by immunohistochemistry and Western blot. The expression levels of TrxR1 in human gastric cancer cells line and gastric mucosa epithelial cells were determined by Western blot and quantitative real-time PCR assays. Then, AGS cells were transfected with siRNA sequences to silence the expression of TrxR1. AGS cells were divided into 3 groups according to different processing negative control group: transfected with NC-siRNA, TRXR1 siRNA interference group 1: transfected with TRXR1-siRNA1, TRXR1 siRNA interference 2 group: transfected with TRXR1-siRNA2. The expression of TrxR1 mRNA in AGS cells of each group was detected by Real-time PCR. The proliferation of AGS cells was determined by MTT and colony formation assays following TrxR1 silencing. RESULTS: TrxR1 mRNA and protein expression levels in gastric cancer tissues were significantly up-regulated compared with adjacent tissues, and were mainly located in the cytoplasm. High expression of TrxR1 was associated with TNM stage and lymph node metastasis, and the overall survival time of patients with high expression of TrxR1 was shorter than those with low expression level. TrxR1 mRNA and protein in AGS cells of TRXR1-siRNA1 group and AGS cells of TRXR1-siRNA2 group were significantly reduced compared with NC-siRNA group (P＜0.05). And AGS cell clone formation and proliferation ability were decreased. CONCLUSION: The high expression of TrxR1 in gastric cancer tissues indicates poor prognosis of patients, and the silencing of TrxR1 can inhibit the proliferation of gastric cancer cells.