Prognosis Of Gastric Carcinoma Research Articles

Reduced expression of E-cadherin correlates with poor prognosis and unfavorable clinicopathological features in gastric carcinoma: a meta-analysis.

Gastric carcinoma (GC) is one of the most fatal human malignancies globally, with a median survival time less than 1 year. E-cadherin exerts a crucial role in the development and progression of GC as an adhesive, invasive suppressor gene. Whether reduced E-cadherin has an impact on prognosis, clinicopathological features for GC has been well studied, but no conclusive results has been obtained. Eligible studies and relevant data were obtained from PubMed, Elsevier, Embase, Cochrane Library and Web of Science databases until June 30, 2023. A fixed- or random-effects model was used to calculate pooled odds ratios (OR) and 95% confidence intervals (CI). Correlation of E-cadherin expression with overall survival (OS), clinicopathological features and risk factors were evaluated. 36 studies fulfilled the selected criteria. 9048 cases were included. This meta-analysis showed that patients with GC with reduced E-cadherin had unfavourable clinicopathological features and poor OS. The pooled ORs of one-, three- and five-year OS were 0.38 (n = 25 studies, 95%CI: 0.25-0.57, Z = 4.61, P < 0.00001), 0.33 (n = 25 studies, 95% CI: 0.23-0.47, Z = 6.22, P < 0.00001), 0.27 (n = 22 studies, 95% CI: 0.18-0.41, Z = 6.23, P < 0.00001), respectively. Moreover, reduced E-cadherin expression significantly correlated with differentiation grade (OR = 0.29, 95% CI: 0.22-0.39, Z = 8.58, P < 0.00001), depth of invasion (OR = 0.49, 95% CI: 0.36-0.66, Z = 4.58, P < 0.00001), lymphatic node metastasis (OR = 0.49, 95% CI: 0.38-0.64, Z = 5.38, P < 0.00001), distant metastasis (OR = 2.24, 95% CI: 1.62-3.09, Z = 4.88, P < 0.00001), peritoneal metastasis (OR = 2.17, 95% CI: 1.39-3.39, Z = 3.40, P = 0.0007), TNM stage (OR = 0.41, 95% CI: 0.28-0.61, Z = 4.44, P < 0.00001), lymphatic vessel invasion (OR = 1.77, 95% CI: 1.11-2.82, Z = 2.39, P = 0.02), vascular invasion (OR = 1.55, 95% CI: 1.22-1.96, Z = 3.58, P = 0.0003), Lauren type (OR = 0.35, 95% CI: 0.21-0.57, Z = 4.14, P < 0.0001), Borrmann classification (OR = 0.50, 95% CI: 0.25-0.99, Z = 1.97, P = 0.048) and tumor size (≥5 cm vs. <5 cm: OR = 1.73, 95% CI: 1.34-2.23, Z = 4.19, P < 0.0001; ≥6 cm vs. <6 cm: OR = 2.29, 95% CI: 1.51-3.49, Z = 3.87, P = 0.0001). No significant association was observed between reduced E-cadherin expression and liver metastasis, perineural invasion, alcohol consumption, smoking status, familial history, Helicobacter pylori (HP) infection. The reduced expression of E-cadherin is significantly correlated with poor OS and unfavourable clinicopathological features in GC. The expression level of E-cadherin not only serves as a predictor for disease progression and prognosis in GC but also emerges as a novel therapeutic target.

Identification of Key Genes Associated with Tumor Microenvironment Infiltration and Survival in Gastric Adenocarcinoma via Bioinformatics Analysis.

Gastric carcinoma (GC) is the fifth most commonly diagnosed cancer and the third leading cause of cancer-related deaths globally. The tumor microenvironment plays a significant role in the pathogenesis, prognosis, and response to immunotherapy. However, the immune-related molecular mechanisms underlying GC remain elusive. Bioinformatics analysis of the gene expression of GC and paracancerous healthy tissues from the same patient was performed to identify the key genes and signaling pathways, as well as their correlation to the infiltration of the tumor microenvironment (TME) by various immune cells related to GC development. We employed GSE19826, a gene expression profile from the Gene Expression Omnibus (GEO), for our analysis. Functional enrichment analysis of Differentially Expressed Genes (DEGs) was conducted using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes database. Cytoscape software facilitated the identification of nine hub DEGs, namely, FN1, COL1A1, COL1A2, THBS2, COL3A1, COL5A1, APOE, SPP1, and BGN. Various network analysis algorithms were applied to determine their high connectivity. Among these hub genes, FN1, COL1A2, THBS2, COL3A1, COL5A1, and BGN were found to be associated with a poor prognosis for GC patients. Subsequent analysis using the TIMER database revealed the infiltration status of the TME concerning the overexpression of these six genes. Specifically, the abovementioned genes demonstrated direct correlations with cancer-associated fibroblasts, M1 and M2 macrophages, myeloid-derived suppressor cells, and activated dendritic cells. Our findings suggest that the identified hub genes, particularly BGN, FN1, COL1A2, THBS2, COL3A1, and COL5A1, play crucial roles in GC prognosis and TME cell infiltration. This comprehensive analysis enhances our understanding of the molecular mechanisms underlying GC development and may contribute to the identification of potential therapeutic targets and prognostic markers for GC patients.

Hsa_Circ_0002762 may be a New Marker for the Gastric Cancer Diagnosis and Prognosis.

The global incidence and mortality rate of gastric carcinoma (GC) persists at elevated levels, often manifesting no overt symptoms in its early stages. Hsa_circ_0002762 has been identified as an important modulator in cervical cancer. This study aims to explore its role in the context of GC. A quantitative real-time polymerase chain reaction (qPCR) was implemented to assess the expression level of hsa_circ_0002762. The over-expression was confirmed through an examination of 28 cases of gastric cancer and their corresponding adjacent tissues. In addition, plasma samples from 78 healthy individuals, from 45 benign gastritis patients, and from 106 gastric cancer patients were collected, and the diagnostic efficacy was assessed by analyzing the receiver operating characteristic (ROC) curve. Simultaneously, postoperative specimens from 36 GC cases were collected, and a Kaplan-Meier survival analysis curve was used to evaluate the prognosis of GC. The study revealed an up-regulation in the expression of hsa_circ_0002762 in gastric cancer plasma and tissues. The area under the receiver operating characteristic (ROC) curve for serum hsa_circ_0002762 was 0.784 (95% CI: 0.719 - 0.851), indicating a higher diagnostic efficiency compared to CEA (0.687, 95% CI: 0.611 - 0.763) and CA199 (0.699, 95% CI: 0.625 - 0.744). Combining these three biomarkers demonstrated an increased sensitivity in the diagnostic effectiveness. Finally, postoperative dynamic monitoring revealed a practical utility in predicting the clinical prognosis using serum has_circ_0002762. The findings from our study suggest that hsa_circ_0002762 holds promise as a novel diagnostic and prognostic marker for individuals with GC.

YAP/TEAD-induced PRIM1 contributes to the progression and poor prognosis of gastric carcinoma

Gastric carcinoma has a poor prognosis and low survival rate. PRIM1 is closely associated with the origin of DNA replication and serves as a carcinogenic factor in multiple tumors. This study aimed to explore the functions of PRIM1 in the progression of gastric carcinoma. The luciferase reporter assay examined the regulatory effect of YAP1/TEAD4 on PRIM1. A xenograft tumor mouse model was constructed to observe cancer cell proliferation in vivo. The upregulation of PRIM1 was found in gastric carcinoma cells and tissues, and it was associated with poor prognosis. Silencing PRIM1 inhibited cell proliferation, arrested the cell cycle, and upregulated Cdc25, Cyclin B, and Cdc2 expression. In addition, apoptosis was increased upon PRIM1 knockdown, accompanied by increased protein levels of cleaved caspase-3 and caspase-8. In vivo, knockdown of PRIM1 suppressed the growth of xenograft tumors formed by gastric carcinoma cells. Moreover, PRIM1 silencing elevated the chemosensitivity of gastric carcinoma cells. By investigating molecular events downstream of the Hippo signaling pathway, we found that PRIM1 was a target gene of the YAP1/TEAD4 transcriptional regulatory complex. PRIM1 represents a novel target for gastric carcinoma therapeutic approaches.

Identifying mitophagy-related genes as prognostic biomarkers and therapeutic targets of gastric carcinoma by integrated analysis of single-cell and bulk-RNA sequencing data

Gastric carcinoma (GC) is the fourth leading cause of cancer-related mortality worldwide. Patients with advanced GC tend to have poor prognoses and shortened survival. Finding novel predictive biomarkers for GC prognosis is an urgent need. Mitophagy is the selection degradation of damaged mitochondria to maintain cellular homeostasis, which has been shown to play both pro- and anti-tumor effects. This study combined single-cell sequencing data and transcriptomics to screen mitophagy-related genes (MRGs) associated with GC progression and analyze their clinical values. Reverse transcription-quantitative PCR (RT-qPCR) and immunochemistry (IHC) further verified gene expression profiles. A total of 18 DE-MRGs were identified after taking an intersection of single-cell sequencing data and MRGs. Cells with a higher MRG score were mainly distributed in the epithelial cell cluster. Cell-to-cell communications among epithelial cells with other cell types were significantly upregulated. We established and validated a reliable nomogram model based on DE-MRGs (GABARAPL2 and CDC37) and traditional clinicopathological parameters. GABARAPL2 and CDC37 displayed different immune infiltration states. Given the significant correlation between hub genes and immune checkpoints, targeting MRGs in GC may supplement more benefits to patients who received immunotherapy. In conclusion, GABARAPL2 and CDC37 may be prognostic biomarkers and candidate therapeutic targets of GC.

Prognostic significance of N6-methyladenosine-modified related chemotransferase METTL3 in gastric carcinoma: Evidence from meta-analysis.

N6-methyladenosine (m6A) methylation is known as the research hotspot for tumor epimodification, and its associated methyltransferase-like3 (METTL3) is significantly differentially expressed in gastric carcinoma, but its clinical value has not been summarized. This meta-analysis aimed to evaluate the prognostic significance of METTL3 in gastric carcinoma. Databases, including PubMed, EMBASE (Ovid platform), Science Direct, Scopus, MEDLINE, Google Scholar, Web of Science, and Cochrane Library, were used to identify relevant eligible studies. The endpoints included overall survival, progression-free survival, recurrence-free survival, post-progression survival, and disease-free survival. Hazard ratios (HR) with 95% confidence intervals (CI) were used to correlate METTL3 expression with prognosis. Subgroup and sensitivity analyses were performed. Seven eligible studies involving 3034 gastric carcinoma patients were recruited for this meta-analysis. The analysis showed that high METTL3 expression was associated with significantly poorer overall survival (HR = 2.37, 95% CI 1.66-3.39, P < 0.01) and unfavorable disease-free survival (HR = 2.58, 95% CI 1.97-3.38, P < 0.01), as did unfavorable progression-free survival (HR = 1.48, 95% CI 1.19-1.84, P < 0.01)/recurrence-free survival (HR = 2.62, 95% CI 1.93-5.62, P < 0.01)/post-progression survival (HR = 1.53, 95% CI 1.22-1.91, P < 0.01). Subgroup analysis found that high METTL3 expression was associated with worse overall survival in patients with Chinese (HR = 2.21, 95% CI 1.48-3.29, P < 0.01), in studies with sample source from formalin-fixed, paraffin-embedded tissues (HR = 2.66, 95% CI 1.79-3.94, P < 0.01), and the reported directly from articles group (HR = 2.42, 95% CI 1.66-3.53, P < 0.01). The subgroup analysis that was performed based on sample size, detected method, and follow-up showed the same results. High expression of METTL3 predicts poor prognosis in gastric carcinoma, indicating promise for METTL3 as a prognostic biomarker.Systematic review registration: https://www.crd.york.ac.uk/prospero, ID = CRD42023408519.

Artificial intelligence in theranostics of gastric cancer, a review.

Gastric cancer (GC) is one of the commonest cancers with high morbidity and mortality in the world. How to realize precise diagnosis and therapy of GC owns great clinical requirement. In recent years, artificial intelligence (AI) has been actively explored to apply to early diagnosis and treatment and prognosis of gastric carcinoma. Herein, we review recent advance of AI in early screening, diagnosis, therapy and prognosis of stomach carcinoma. Especially AI combined with breath screening early GC system improved 97.4 % of early GC diagnosis ratio, AI model on stomach cancer diagnosis system of saliva biomarkers obtained an overall accuracy of 97.18 %, specificity of 97.44 %, and sensitivity of 96.88 %. We also discuss concept, issues, approaches and challenges of AI applied in stomach cancer. This review provides a comprehensive view and roadmap for readers working in this field, with the aim of pushing application of AI in theranostics of stomach cancer to increase the early discovery ratio and curative ratio of GC patients.

PSMA1 mediates tumor progression and poor prognosis of gastric carcinoma by deubiquitinating and stabilizing TAZ

The deubiquitinating enzyme family in tumor progression play important role in intracellular protein degradation. The proteasome subunit alpha type 1 (PSMA1) has been reported to act as an oncogene in several human cancers. The present study aimed to reveal the functional significance of PSMA1 in gastric cancer (GC) progression and the underlying mechanisms. The expression of PSMA1 in human GC samples and GC cell lines was examined by western blot analysis, real-time PCR, immunohistochemistry (IHC), and in vitro ubiquitination assays and established a xenograft mouse model. We found that PSMA1 was upregulated in GC and promoted proliferation, migration and invasion in GC cells. Herein, we report transcriptional co-activator with PDZ-binding motif (TAZ) was a downstream gene of PSMA1. Mechanistically, PSMA1 directly interacted with and stabilized TAZ via deubiquitination in GC. Furthermore, we found that TAZ was the essential mediator of PSMA1-modulated oncogenic activity in vitro and in vivo. Examination of clinical samples confirmed that elevated mediators of PSMA1, concomitant with increased TAZ abundance, correlate with human GC progression. These data suggested that PSMA1 promotes GC progression and proliferation by deubiquitinating TAZ. PSMA1 promotes GC progression and proliferation regarding PSMA1-mediated deubiquitinating enzyme activity and suggest potential therapeutic targets for GC management.

Effects of mRNA expression of five Notch ligands on prognosis of gastric carcinoma

Notch ligands are expression changes in a great many malignancies including gastric cancer (GC) frequently. The prognostic value of each Notch ligands in GC patients remains lack of large sample data results. In present research, we researched the prognostic value of Notch ligands in GC patients in order to fill the shortage areas. We used an online database (http://kmplot.com/analysis/index.php?p=service&cancer=gastric) to identify the relationship between mRNA expression of each Notch ligand and overall survival (OS) in GC. We analyze the relevance of overall survival and clinical data which includes gender, Lauren's classification, differentiation, clinical stage and treatment. The study found that high DLL1, DLL3, DLL4 and JAG2 mRNA expression were tied to worse OS in all GC patients followed up for 10 years. There is no significant relevance to the expression of JAG1 mRNA and OS in patients with GC. We also did a survey of each Notch ligands in different clinical and pathological features present different prognosis. The information will help to better understand the biology of gastric cancer heterogeneity, provide more accurate prognostic evaluation tools and provide new targets for targeted drug development besides.

A Pilot Study of Prognostic Value of Metastatic Lymph Node Count and Size in Patients with Different Stages of Gastric Carcinoma.

BackgroundThe correlation between the preoperative lymph node count (LNC) on multidetector computed tomography (MDCT) and the prognosis of gastric carcinoma (GC) remains to be defined. This research aims to evaluate the prognostic value of LNC on MDCT in GC patients based on tumor-node-metastasis (TNM) staging, using different size criteria for counting.MethodsThe clinical data of 126 patients with gastric adenocarcinoma undergoing gastrectomy were retrospectively analyzed. Lymph nodes greater than 8mm and 5mm on MDCT were counted and recorded. The prognostic implications of LNC on MDCT for patient survival were analyzed according to different size criteria for counting and tumor TNM staging.ResultsWhen 8mm was used as the counting criterion, LNC on MDCT had no significant effect on the overall survival (OS) of the entire cohort. In addition, the OS of T1–T2 GC patients with LNC on MDCT ≥1 was significantly worse than that of patients with LNC on MDCT <1. When 5mm was used as the counting criterion, LNC on MDCT was found to be significantly associated with the OS of the entire cohort. In the subgroup analysis, patients with relatively advanced (T3-T4, N+ and III) GC with LNC on MDCT >7 showed a significantly worse OS than those with LNC on MDCT ≤7. LNC on MDCT >7 with 5mm as the counting criterion and Stage III were independent risk factors for adverse prognosis.ConclusionThe prognostic value of LNC on MDCT based on different size criteria varies in patients with different stages of GC. LNC of a smaller size (5mm) on MDCT may be a prognostic factor for patients with relatively advanced GC.

The relationship of different preoperative inflammatory markers with the prognosis of gastric carcinoma

BackgroundIt is aimed to determine the prognostic values of preoperative inflammatory biomarkers in patients undergoing curative surgery for gastric carcinoma and to contribute to the development of prognostic modeling. ObjectiveTo investigate the effect of various different preoperative inflammatory markers on the prognosis of gastric carcinoma. Material and methodThe medical data and the mortality status of 91 patients who underwent total or subtotal gastrectomy operation for gastric carcinoma at Mersin City Training and Research Hospital between 2016 and 2020 were retrospectively reviewed from the hospital records and patient files. The patients' demographic characteristics, tumor location, histopathological diagnosis, pathological stage, tumor markers, and preoperative inflammatory and hematological markers were analyzed. Based on these data, tumor stage, metastatic lymph node ratio (MLR), lactate dehydrogenase albumin ratio (LAR), neutrophil-lymphocyte ratio (NLR), and platelet lymphocyte ratio (PLR) were calculated. The relationship between these parameters and postoperative survival was analyzed. Statistical analyses were performed with IBM SPSS for Windows, version 17.0 (IBM Corporation, Armonk, New York, United States). ResultsThe correlation analysis of the parameters affecting survival showed that, in addition to an advanced tumor stage, inflammatory parameters like NLR, PLR, and LAR adversely affected survival. ConclusionPreoperative NLR, PLR, LAR, and advanced tumor stage may help determine the survival of gastric carcinoma patients. Multiple studies with larger series are needed on this subject.

Structure–activity relationship and in silico development of c‐Met kinase inhibitors

AbstractOverexpression and concomitant drug resistance of c‐Met kinase are strongly associated with poor prognosis in gastric carcinoma. This needs the further development of existing lead compounds against c‐Met. Herein, we conducted molecular modeling studies of 4‐phenoxypyridine derivatives as c‐Met kinase inhibitors using docking, molecular dynamics (MD), and binding energy estimation to examine receptor–ligand interaction, complex stability, and binding affinity. We developed statistically significant three‐dimensional structure–activity relationship models (3D‐QSAR) to correlate the physicochemical characteristics of the inhibitors with their biological activities. The field effects of the chemical descriptors were determined as contour polyhedrons and emphasized as SAR. Thirty new compounds were designed according to the SAR scheme, and their activities were predicted using the 3D‐QSAR model. The designed compounds with higher predicted pIC50 values than the most active compounds in the dataset were subjected to absolute binding free‐energy evaluation by free energy perturbation (FEP) method.

Acetone Compression Improves Lymph Node Harvesting.

To the editor The review article by Díaz del Arco et al1 provides a comprehensive review of the methods used for the surgical removal and gross room retrieval of lymph nodes from gastric carcinoma excisions, TNM staging of gastric carcinoma, and multiple additional histologic features of lymph node metastases used for accurate prognosis of gastric carcinoma. The authors mention methods beyond manual palpation to improve lymph node harvesting, such as fat clearing. Omitted from the comprehensive review is an entirely new method for lymph node harvesting first reported in the United States in 2004.2 This method, currently used more extensively in Germany (the early reports are based on over 700 cases), is the “acetone compression” method for lymph node retrieval.3-5 The acetone compression method decreases adipose tissue volume through dissolving fat in fat solvents (elution) and extracting the dissolved fat with compression. Tissue volume is decreased up...

Correlation analysis between preoperative systemic immune inflammation index and prognosis of patients after radical gastric cancer surgery: based on propensity score matching method

BackgroundTo explore the correlation between the preoperative systemic immune inflammation index (SII) and the prognosis of patients with gastric carcinoma (GC).MethodsThe clinical data of 771 GC patients surgically treated in the Department of Gastrointestinal Surgery, Qinghai University Affiliated Hospital from June 2010 to June 2015 were retrospectively analyzed, and their preoperative SII was calculated. The optimal cut-off value of preoperative SII was determined using the receiver operating characteristic (ROC) curve, the confounding factors between the two groups were eliminated using the propensity score matching (PSM) method, and the correlation between preoperative SII and clinicopathological characteristics was assessed by chi-square test. Moreover, the overall survival was calculated using Kaplan-Meier method, the survival curve was plotted, and log-rank test was performed for the significance analysis between the curves. Univariate and multivariate analyses were also conducted using the Cox proportional hazards model.ResultsIt was determined by the ROC curve that the optimal cut-off value of preoperative SII was 489.52, based on which 771 GC patients were divided into high SII (H-SII) group and low SII (L-SII) group, followed by PSM in the two groups. The results of Kaplan-Meier analysis showed that before and after PSM, the postoperative 1-, 3-, and 5-year survival rates in L-SII group were superior to those in H-SII group, and the overall survival rate had a statistically significant difference between the two groups (P < 0.05). Before PSM, preoperative SII [hazard ratio (HR) = 2.707, 95% confidence interval (CI) 2.074-3.533, P < 0.001] was an independent risk factor for the prognosis of GC patients. After 1:1 PSM, preoperative SII (HR = 2.669, 95%CI 1.881–3.788, P < 0.001) was still an independent risk factor for the prognosis of GC patients.ConclusionsPreoperative SII is an independent risk factor for the prognosis of GC patients. The increase in preoperative SII in peripheral blood indicates a worse prognosis.

TNFAIP6 Promotes Gastric Carcinoma Cell Invasion via Upregulating PTX3 and Activating the Wnt/β-Catenin Signaling Pathway.

Tumor metastasis is a fundamental cause of the poor prognosis of gastric carcinoma (GC). In order to study the problems affecting metastasis and recurrence of gastric cancer, the paper expose that TNF alpha induced protein 6 (TNFAIP6) is aberrantly overexpressed in GC, and patients with high-TNFAIP6 levels exhibited inferior overall survival. Mechanistically, overexpression of TNFAIP6 raised β-catenin ectopic nuclear distribution and activated the Wnt/β-catenin signal pathway. The experimental results show that TNFAIP6 facilitates the aggressive potential of GC cells through modulating PTX3 expression.

Inflammation-Related Long Non-Coding RNA Signature Predicts the Prognosis of Gastric Carcinoma.

Background: Gastric carcinoma (GC) is a molecularly and phenotypically highly heterogeneous disease, making the prognostic prediction challenging. On the other hand, Inflammation as part of the active cross-talk between the tumor and the host in the tumor or its microenvironment could affect prognosis. Method: We established a prognostic multi lncRNAs signature that could better predict the prognosis of GC patients based on inflammation-related differentially expressed lncRNAs in GC. Results: We identified 10 differently expressed lncRNAs related to inflammation associated with GC prognosis. Kaplan-Meier survival analysis demonstrated that high-risk inflammation-related lncRNAs signature was related to poor prognosis of GC. Moreover, the inflammation-related lncRNAs signature had an AUC of 0.788, proving their utility in predicting GC prognosis. Indeed, our risk signature is more precise in predicting the prognosis of GC patients than traditional clinicopathological manifestations. Immune and tumor-related pathways for individuals in the low and high-risk groups were further revealed by GSEA. Moreover, TCGA based analysis revealed significant differences in HLA, MHC class-I, cytolytic activity, parainflammation, co-stimulation of APC, type II INF response, and type I INF response between the two risk groups. Immune checkpoints revealed CD86, TNFSF18, CD200, and LAIR1 were differently expressed between lowand high-risk groups. Conclusion: A novel inflammation-related lncRNAs (AC015660.1, LINC01094, AL512506.1, AC124067.2, AC016737.1, AL136115.1, AP000695.1, AC104695.3, LINC00449, AC090772.1) signature may provide insight into the new therapies and prognosis prediction for GC patients.

Expression of CyclinD1, CDC25B and p27 protein in gastric carcinoma And it s clinical significance

Background: Gastric cancer is a common digestive tract tumor in our China, with high morbidity and mortality. Similar with other tumors, the occurrence of gastric cancer was also a complex pathophysiological process, regulated by a variety of oncogenes and tumor suppressor gene. Aims and Objectives: This study aims to investigate the expression of cyclin D1, CDC25B, and p27 in gastric carcinoma and to study their relationship with the occurrence and development of gastric cancer. Materials and Methods: SP immunohistochemical and Western blot analysis were used to detect the expression of cyclin D1, CDC25B, and p27 in 42 cases of gastric carcinoma, 42 cases of paracancer, and 42 cases of normal gastric tissue and then their relationship with clinical and pathological factors was analyzed. Results: (1) The expression of cyclin D1 increased gradually in normal gastric tissue, paracancer, and gastric carcinoma (P&gt;0.05). The expression of CDC25B was higher in gastric carcinoma (P&lt;0.05) while p27 was lower (P&lt;0.05). (2) The result of Western blot shows that the expression of cyclin D1 and CDC25B was higher in gastric carcinoma than that in normal gastric tissue while p27 lower in gastric carcinoma (P&lt;0.05), same with immunohistochemical. (3) The expressions of cyclin D1 and CDC25B had correlation with lymph nodes metastasis, and p27 had correlation with degrees of pathological differentiation, invasion depth, and lymph nodes metastasis. (4) There was a positive relationship between the expression of cyclin D1 and CDC25B in same sample (r=−0.392, P&lt;0.05). Conclusion: Expression of cyclin D1, CDC25B, and p27 protein can be helpful in the prediction of the biological behavior and prognosis of gastric carcinoma.

Kinase DYRK2 acts as a regulator of autophagy and an indicator of favorable prognosis in gastric carcinoma

Gastric cancer (GC) is the third leading cause of cancer-related death worldwide; therefore, new and more specific molecules for GC are needed. Here, we found that dual specificity tyrosine phosphorylation regulated kinase 2 (DYRK2) may be a specific marker for GC. Immunohistochemistry (IHC) and statistical and bioinformatics analyses were conducted to detect DYRK2 expression in stomach tissues. The role of DYRK2 in GC was analyzed with a nude mouse model and CCK-8, wound healing and Transwell assays. Western blotting and immunofluorescence experiments were also performed to elucidate the relationship between DYRK2 expression and both epithelial-mesenchymal transition (EMT) and autophagy progression. We found that DYRK2 expression in GC tissues was lower than that in benign or normal tissues, and patients with high DYRK2 expression had a good prognosis. The in vitro results showed that DYRK2 expression inhibited the tumorigenic activities of GC, including proliferation, migration, and invasion. By analyzing the expression of EMT markers after altering DYRK2 expression, we observed that DYRK2 inhibits the occurrence of EMT. The nude mouse model revealed that DYRK2 inhibits tumor growth. Finally, we used Western blotting and immunofluorescence assays and found that DYRK2 promotes autophagy. Based on these data, DYRK2 may be a good reference indicator for the clinical diagnosis of GC.

Identification of lncRNA-associated competing endogenous RNA networks for occurrence and prognosis of gastric carcinoma.

BackgroundGastric cancer (GC) is one of the common digestive malignancies worldwide and causes a severe public health issue. So far, the underlying mechanisms of GC are largely unclear. Thus, we aim to identify the long non‐coding RNA (lncRNA)‐associated competing endogenous RNA (ceRNA) for GC.MethodsTCGA database was downloaded and used for the identification of differentially expressed (DE) lncRNAs, miRNAs, and mRNAs, respectively. Then, the ceRNA network was constructed via multiple online datasets and approaches. In addition, various in vitro assays were carried out to validate the effect of certain hub lncRNAs.ResultsWe constructed a ceRNA network, including 76 lncRNAs, 18 miRNAs, and 159 mRNAs, which involved multiple critical pathways. Next, univariate and multivariate analysis demonstrated 11 lncRNAs, including LINC02731, MIR99AHG, INHBA‐AS1, CCDC144NL‐AS1, VLDLR‐AS1, LIFR‐AS1, A2M‐AS1, LINC01537, and LINC00702, and were associated with OS, and nine of those lncRNAs were considered as hub lncRNAs involved in the sub‐ceRNA network. The in vitro assay indicated two lncRNAs, INHBA‐AS1 and CCDC144NL‐AS1, which were positively related to the GC aggressive features, including proliferation, invasion, and migration.ConclusionsWe identified nine hub lncRNAs and the associated ceRNA network related to the prognosis of GC, and then validated two out of them as promising oncogenes in GC.

An Advanced Systems Pharmacology Strategy Reveals AKR1B1, MMP2, PTGER3 as Key Genes in the Competing Endogenous RNA Network of Compound Kushen Injection Treating Gastric Carcinoma by Integrated Bioinformatics and Experimental Verification.

Gastric carcinoma (GC) is a severe tumor of the digestive tract with high morbidity and mortality and poor prognosis, for which novel treatment options are urgently needed. Compound Kushen injection (CKI), a classical injection of Chinese medicine, has been widely used to treat various tumors in clinical practice for decades. In recent years, a growing number of studies have confirmed that CKI has a beneficial therapeutic effect on GC, However, there are few reports on the potential molecular mechanism of action. Here, using systems pharmacology combined with proteomics analysis as a core concept, we identified the ceRNA network, key targets and signaling pathways regulated by CKI in the treatment of GC. To further explore the role of these key targets in the development of GC, we performed a meta-analysis to compare the expression differences between GC and normal gastric mucosa tissues. Functional enrichment analysis was further used to understand the biological pathways significantly regulated by the key genes. In addition, we determined the significance of the key genes in the prognosis of GC by survival analysis and immune infiltration analysis. Finally, molecular docking simulation was performed to verify the combination of CKI components and key targets. The anti-gastric cancer effect of CKI and its key targets was verified by in vivo and in vitro experiments. The analysis of ceRNA network of CKI on GC revealed that the potential molecular mechanism of CKI can regulate PI3K/AKT and Toll-like receptor signaling pathways by interfering with hub genes such as AKR1B1, MMP2 and PTGERR3. In conclusion, this study not only partially highlighted the molecular mechanism of CKI in GC therapy but also provided a novel and advanced systems pharmacology strategy to explore the mechanisms of traditional Chinese medicine formulations.