Gastric adenocarcinoma (GAC), also known as stomach adenocarcinoma (STAD), is one of the most lethal malignancies in the world. It is vital to classify and detect the hub genes and key pathways ...participated in the initiation and progression of GAC. In this study, we collected and sequenced 15 pairs of GAC tumor tissues and the adjacent normal tissues. Differentially expressed genes (DEGs) were analyzed and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) analysis were used to annotate the unique biological significance and important pathways of enriched DEGs. Moreover, we constructed the protein-protein interaction (PPI) network by Cytoscape and conducted KEGG enrichment analysis of the prime module. We further applied the TCGA database to start the survival analysis of these hub genes by Kaplan-Meier estimates. Finally, we obtained total 233 DEGs consisted of 64 up-regulated genes and 169 down-regulated genes. GO enrichment analysis found that DEGs most significantly enriched in single organism process, extracellular region, and extracellular region part. KEGG pathway enrichment analysis suggested that DEGs most significantly enriched in Protein digestion and absorption, Gastric acid secretion, and ECM-receptor interaction. Furthermore, the PPI network showed that the top 10 hub genes in GAC were IL8, COL1A1, MMP9, SST, COL1A2, TIMP1, FN1, SPARC, ALDH1A1, and SERPINE1 respectively. The prime gene interaction module in PPI network was enriched in protein digestion and absorption, ECM receptor interaction, the PI3K-Akt signaling pathway, and pathway in cancer. Survival analysis based on the TCGA database found that the expression of the FN1, SERPINE1, and SPARC significantly predicted poor prognosis of GAC. Collectively, we identified several hub genes and key pathways associated with GAC initiation and progression by analyzing the microarray data on DEGs, which provided a detailed molecular mechanism underlying GAC occurrence and progression.
Pseudouridine synthase 7 (PUS7) may play key roles in cancer development. However, few studies have been conducted in this area. In the present study, we explored the function and potential ...mechanisms of PUS7 in colorectal cancer (CRC) progression. We found that PUS7 had higher expression in CRC tissues and cell lines. Clinically, high expression of PUS7 was associated with an unfavorable prognosis for CRC patients. Functionally, knockdown of PUS7 suppressed the proliferation of CRC cells in vitro and inhibited tumorigenicity in vivo. Mechanistically, RNA sequencing and coimmunoprecipitation (Co‐IP) indicated that PUS7 exhibited oncogenic functions through the interaction of Sirtuin 1 (SIRT1) and activated the Wnt/β‐catenin signaling pathway. Thus, our findings suggest that PUS7 promotes the proliferation of CRC cells by directly stabilizing SIRT1 to activate the Wnt/β‐catenin pathway.
The long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is overexpressed in numerous cancers. However, whether MALAT1 is regulated and the related mechanisms in ...gastric cancer remain unclear.
Immunohistochemistry and qRT-PCR analyses were used to detect the expression levels of UPF1 and MALAT1 in gastric cancer and adjacent normal tissues. MTT, cell cycle, apoptosis and transwell assays were performed to examine the effects of UPF1 on cell cycle progression, cell proliferation, apoptosis, migration and invasion. Additionally, sodium bisulfate sequencing was used to test the promoter hypermethylation on UPF1 in gastric tumor tissues. Finally, RNA immunoprecipitation and luciferase reporter analyses demonstrated that UPF1 directly bound with MALAT1.
The expression of UPF1 was significantly downregulated in gastric cancer and negatively correlated with MALAT1 expression. Patients with lower expression of UPF1 had poorer prognosis than those with higher expression. Overexpression of UPF1 inhibited cell proliferation, cell cycle progression, cell migration and invasion, and promoted cell apoptosis in gastric cancer cells. Moreover, the UPF1-mediated inhibition of gastric cancer progression was reversed by overexpression of MALAT1. A profound downregulation of UPF1 in gastric tumor tissues was due to promoter hypermethylation. Overexpression of UPF1 increased nonsense-mediated mRNA decay (NMD) efficiency and thus led to downregulation of MALAT1.
Our results demonstrate that UPF1 is a potential modulator of MALAT1 and that UPF1/MALAT1 pathway could be a therapeutic target for gastric cancer.
Gastric cancer (GC) is fifth most frequently diagnosed cancer and second leading cause of cancer in China. More than 80% of GC are diagnosed at an advanced stage due to low uptake rate of invasive ...screening method. The performance of methylated SFRP2 test was evaluated in 236 plasma samples, including 92 patients with GC, 16 intestinal metaplasia patients, 26 gastric fundic gland polyp patients, 13 small adenoma patients, 39 hyperplastic polyp patients, and 50 control patients. The sensitivity of plasma methylated SFRP2 was compared to serum CEA, CA72-4, CA19-9, and CA242 results in 79 patients with GC. The sensitivities for detecting GC and gastric intestinal metaplasia by methylated SFRP2 test were 60.9% and 56.3% with a specificity of 86.0%. Methylated SFRP2 test had significantly higher positive detection rate for patients with GC than gastric fundic gland polyp, small adenoma, and hyperplastic polyp patients. In 79 patients with GC, the sensitivities of CEA, CA72-4, CA19-9, and CA242 for detecting GC were 22.8%, 16.5%, 12.7%, and 11.4%. In comparison, the sensitivity of methylated SFRP2 test for detecting GC was 58.2%. Plasma methylated SFRP2 test may become a valuable tool for the noninvasive detection of GC and precursor lesions and showed higher sensitivity than serum tumor markers.
: A number of plasma methylated DNA biomarkers related to colorectal cancer (CRC) have been identified. However, the effect of methylation level in leukocytes on plasma-based methylation test was ...rarely reported.
: Blood samples from 213 individuals including 91 CRC patients were collected and separated into 3.5 mL of plasma and paired leukocyte fractions. DNA were extracted from plasma and leukocytes and bisulfite converted, followed by ColoDefense test that detects methylated
(m
) and methylated
(m
) simultaneously in a single qPCR reaction.
: Both m
and m
levels in leukocytes exhibited no significant difference among CRC, benign tumors and healthy controls. However, m
and m
levels in plasma were significantly higher in CRC group than those in other groups. The sensitivities of m
and m
alone for detecting CRC with plasma samples were 75.8% and 60.4% with specificities of 94.7% and 86.8%, respectively. These two markers in combination exhibited an improved sensitivity of 85.7% for CRC detection with a specificity of 86.8%, mostly attributable to increased sensitivity of 81.8% for detecting stage 0-II CRC. AUC values for m
and m
alone were 0.864 (95% CI: 0.798 - 0.929) and 0.796 (95% CI: 0.719 - 0.874), respectively, but improved to 0.972 (95% CI: 0.949 - 0.996) when combined for ColoDefense test.
: The leukocytes gDNA will not affect the performance of plasma ColoDefense test, and plasma ColoDefense test exhibited high sensitivity and specificity in a validation set, demonstrating its potential as a non-invasive and cost-effective method for CRC early detection.
•A novel non-invasive assay contain two methylated biomarkers in a single qPCR reaction.•SpecColon test has lower cost and is much easier to perform.•Less input plasma by SpecColon test but achieved ...comparable sensitivity and specificity for detecting CRC and AA.
Methylated SFRP2 was previously reported as a non-invasive biomarker for colorectal cancer (CRC) detection with a relatively low sensitivity for early stage CRC. The purpose of this study was to evaluate the performance of a new plasma based CRC screening assay, SpecColon test, which tested methylated SFRP2 and SDC2 simultaneously in a single qPCR reaction, in detecting CRC and advanced adenomas (AA).
One milliliter plasma of 122 CRC patients, 12 AA patients, 93 patients with benign polyps, and 91 normal individuals were collected from the Affiliated Hospital of Xuzhou Medical University, and all samples were examined by SpecColon test.
The sensitivities for detecting AA and CRC by methylated SFRP2 alone were 50.0% (95% CI: 22.2–77.7%) and 63.1% (95% CI: 53.9–71.5%) with a specificity of 90.1% (95% CI: 81.6–95.1%). The sensitivities by methylated SDC2 alone were 33.3% (95% CI: 11.3–64.6%) and 56.6% (95% CI: 47.3–65.4%) with a specificity of 95.6% (95% CI: 88.5–98.6%). However, when methylated SFRP2 and methylated SDC2 were combined, the sensitivities for AA and CRC detection improved to 58.3% (95% CI: 28.6–83.5%) and 76.2% (95% CI: 67.5–83.3%) with a specificity of 87.9% (95% CI: 79.0–93.5%). The positive detection rates of benign polyp group and normal control group showed no significant difference (p > 0.01), whereas AA and CRC groups had significantly higher positive detection rates than normal individual group (p < 0.001).
The sensitivities for AA and early stage CRC by combined test of methylated SFRP2 and methylated SDC2, the so called SpecColon test, improved upon those by either biomarker alone without significant impact on the specificity. It has the potential to become a powerful, convenient and highly effective screening tool for early CRC screening.
Objective
Acute necrotic collection (ANC), acute peripancreatic fluid collection (APFC), pleural effusion, and ascites are common early complications of acute pancreatitis. This study aimed to ...investigate the relationship between 12 serum cytokines and the early complications and severity of acute pancreatitis (AP).
Methods
We retrospectively analyzed the clinical data of 307 patients with AP, and divided them into severe group and mild‐to‐moderate group according to the revised Atlanta classification. Propensity score matching was used to control for confounding factors. Binary logistic regression analysis was used to explore the relationship between cytokine levels and early complications of AP.
Results
Serum levels of interleukin (IL)‐1β, IL‐5, IL‐6, IL‐8, IL‐10, IL‐17, and tumor necrosis factor‐α were significantly higher in the severe acute pancreatitis (SAP) group than in the non‐SAP group (p < .05). After adjusting for confounding factors, the upper quartiles of IL‐6, IL‐8, and IL‐10 were associated with an increased risk of ANC compared with those in the lowest quartile (IL‐6: quartile 3, odds ratio OR = 3.99, 95% confidence interval CI = 1.95–8.16; IL‐8: quartile 4, OR = 2.47, 95% CI = 1.27–4.84; IL‐10: quartile 2, OR = 2.22, 95% CI = 1.09–4.56). APFC was associated with high serum levels of IL‐6 (quartile 3, OR = 1.32, 95% CI = 1.02–1.72), pleural effusions were associated with high serum levels of IL‐1β, IL‐6, IL‐8, and IL‐10 (IL‐1β: quartile 4, OR = 2.36, 95% CI = 1.21–4.58; IL‐6: quartile 3, OR = 4.67, 95% CI = 2.27–9.61; IL‐8: quartile 3, OR = 2.95, 95% CI = 1.51–5.79; IL‐10: quartile 4, OR = 3.20, 95% CI = 1.61–6.36), and high serum levels of IL‐6 and IL‐10 were associated with an increased risk of ascites (IL‐6: quartile 3, OR = 3.01, 95% CI = 1.42–6.37; IL‐10: quartile 3, OR = 2.57, 95% CI = 1.23–5.37).
Conclusion
Serum cytokine levels, including IL‐1β, IL‐6, IL‐8, and IL‐10 may be associated with the occurrence of early complications of AP. In daily clinical practice, IL‐6 may be the most worthwhile cytokine to be detected.
Acute necrotic collection, acute peripancreatic fluid collection, pleural effusion, and ascites are common early complications of acute pancreatitis (AP). This study aimed to investigate the relationship between 12 cytokines and the early complications and severity of AP.
•A novel, cost-effective and non-invasive panel for detection of esophageal cancer, gastric cancer, and colorectal cancer together.•High sensitivity and specificity, and remarkable reproducibility in ...multiple cohorts.•The positive cases detected by the panel can be promptly confirmed through combined colonoscopy and gastroscopy examinations and avoid over follow-up examination.
Target gastrointestinal cancers (GICs), encompassing esophageal cancer (EC), gastric cancer (GC), and colorectal cancer (CRC), originate within a single readily accessible luminal organ system and are diagnosable using endoscopy. However, endoscopy is an invasive procedure with low compliance and no plasma-based DNA methylation assay for the early detection of GICs.
Nine potential DNA methylation markers were identified and evaluated in tissue (n=60) and plasma (n=155) cohorts to select the most suitable markers. A training cohort (n=244) and a validation cohort (n=199), including GICs patients, benign tumors, gastrointestinal polyps, and controls, were enrolled to develop and validate a DNA methylation panel. An independent prospective cohort (n=158) was used to validate the panel's performance and compare it with blood protein tumor markers.
Six out of nine candidate methylation markers with excellent discrimination abilities in both tissue and plasma cohorts were selected for the DNA methylation panel. The panel demonstrated high AUC values of 0.937 (EC), 0.968 (GC), and 0.987 (CRC) in training cohort, and achieved AUC values of 0.921 (EC), 0.921 (GC), and 0.959 (CRC) in validation cohort. Notably, it achieved impressive AUC values of 0.971 and 0.843 for identifying stage I GICs in the training and validation cohorts, respectively. In the prospective cohort, the six-marker panel showed comparable AUC values to CEA, AFP, and CA19-9 (0.935, 0.769, 0.663, and 0.668, respectively).
This study successfully developed and validated a novel, robust, sensitive, and specific plasma-based DNA methylation panel, offering a promising strategy for the early detection of GICs.
Objective. In recent years, the noninvasive serological scoring system has become a research hotspot in predicting hepatic fibrosis and has achieved good results. However, it has rarely been applied ...to the prediction of oesophageal varices. The aim of the study was to evaluate the predictive value of the four following scoring systems in cirrhosis combined with oesophageal varices: aspartate and platelet ratio index (APRI), aspartate aminotransferase-alanine aminotransferase ratio (AAR), FIB-4, and S index. Methods. A total of 153 patients with cirrhosis were categorized into groups with or without oesophageal varices. In addition, cirrhosis patients with oesophageal varices were further divided into mild, moderate, and severe grades. The rank sum test was used to compare the significant differences of APRI, AAR, FIB-4, and S index between the two groups of cirrhosis patients with or without oesophageal varices. A ROC curve was generated to compare the area under the curve of the three groups and to obtain the corresponding optimal prediction value. Moreover, multivariate logistic regression analysis was employed to assess the predictive factors for cirrhosis combined with oesophageal varices. Results. 44 patients had no oesophageal varices and 108 patients had oesophageal varices. Of the 108 patients with oesophageal varices, 43 were mild, 32 were moderate, and 33 were severe. The rank sum test indicated that the APRI, FIB-4, and S index were statistically significant between two groups (P < 0.05), while no significant difference was detected in terms of AAR between the two groups (P > 0.05). In addition, all four scoring systems were statistically significant between nonoesophageal varices group and severe oesophageal varices group (P < 0.05). In the ROC curve of oesophageal varices, the AUC values of APRI, FIB-4, and S index for predicting oesophageal varices were 0.681, 0642, and 0.673, respectively. However, in the ROC curve of severe oesophageal varices, the AUC values of APRI, AAR, FIB-4, and S index were 0.729, 0.648, 0.673, and 0.695, respectively. Multivariate logistic regression analysis indicated that APRI and FIB-4 were predictors of disease progression (P < 0.05). Conclusion. AAR harboured a poor predictive value for oesophageal varices, APRI can be used as a reference index for the prediction of severe oesophageal varices, and the S index harboured potential value in predicting the degree of progression of cirrhosis.
Fexuprazan is a novel potassium-competitive acid blocker (P-CAB). This study aimed to explore the noninferior efficacy and safety of fexuprazan to esomeprazole in treating erosive esophagitis (EE).
...This was a phase III, randomized, double-blind multicenter study. Patients with endoscopically confirmed EE were randomized to receive fexuprazan 40 mg or esomeprazole 40 mg once a daily for 4-8 weeks. The healing rates of EE, symptom response, GERD-health-related quality life (GERD-HRQL), and treatment-emergent adverse events (TEAEs) were compared between fexuprazan group and esomeprazole group.
A total of 332 subjects were included in full analysis set (FAS) and 311 in per-protocol set (PPS). The healing rates of fexuprazan and esomeprazole groups at 8 weeks were 88.5% (146/165) and 89.0% (145/163), respectively, in FAS and 97.3% (145/149) and 97.9% (143/146), respectively, in PPS. Noninferiority of fexuprazan compared with esomeprazole according to EE healing rates at 8 weeks was demonstrated in both FAS and PPS analysis. No significant difference was found between groups in EE healing rates at 4 weeks, symptom responses, and changes of GERD-HRQL. The incidence of drug-related AEs was 19.4% (32/165) in fexuprazan arm and 19.6% (32/163) in esomeprazole arm.
This study demonstrated noninferior efficacy of fexuprazan to esomeprazole in treating EE. The incidence of TEAEs was similar between fexuprazan and esomeprazole. Trial registration number NCT05813561.
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