Digestive System Malignancies Research Articles

Xanthatin suppresses pancreatic cancer cell growth via the ROS/RBL1 signaling pathway: In vitro and in vivo insights

BackgroundAs a malignant digestive system tumor, pancreatic cancer has a high mortality rate. Xanthatin is a sesquiterpene lactone monomer compound purified from the traditional Chinese herb Xanthium strumarium L. It has been reported that Xanthatin exhibits inhibitory effects on various cancer cells in retinoblastoma, glioma, hepatoma, colon cancer, lung cancer, as well as breast cancer. However, in pancreatic cancer cells, only one report exists on the suppression of Prostaglandin E2 synthesis and the induction of caspase 3/7 activation in Xanthatin-treated MIA PaCa-2 cells, while systematic in vitro and in vivo investigations and related mechanisms have yet to be explored. PurposeThis research aims to explore the in vitro and in vivo effects of Xanthatin on pancreatic cancer and its molecular mechanisms. MethodsThe anticancer effects and mechanisms of Xanthatin on pancreatic cancer cells were assessed through employing cell counting kit-8 (CCK-8) assay, lactate dehydrogenase (LDH) assay, carboxyfluorescein diacetate succinimidyl ester (CFDA SE) cell proliferation assay, colony formation assay, wound healing assay, transwell assay, Annexin V-FITC/propidium iodide (PI) dual staining, Hoechst nuclear staining, Western blot analysis, phosphoproteomics, and reactive oxygen species (ROS) measurement. The in vivo anticancer effects of Xanthatin on pancreatic cancer cells were studied using a nude mouse model. ResultsThe present study showed that Xanthatin can prevent the proliferation and metastasis of pancreatic cancer cells and trigger the exposure of phosphatidylserine (PS), chromatin condensation, and caspase activation, thereby inducing apoptosis. Phosphoproteomic analysis indicated that Xanthatin inhibits the phosphorylation of the proliferation-associated protein RBL1, and oxidative stress can lead to RBL1 dephosphorylation. Further investigation revealed that Xanthatin significantly upregulates ROS levels in pancreatic cancer cells, and the antioxidant N-acetylcysteine (NAC) can reverse Xanthatin-induced cell proliferation inhibition and apoptosis. In addition, Xanthatin can suppress pancreatic cancer cell growth in a xenograft nude mouse model with low toxicity to the mice. ConclusionXanthatin may inhibit the proliferation of pancreatic cancer cells and trigger apoptosis through the ROS/RBL1 signaling pathway.

The underlying regulatory mechanisms of colorectal carcinoma by combining Vitexin and Aspirin: based on systems biology, molecular docking, molecular dynamics simulation, and in vitro study.

Colorectal cancer (CRC) is a highly prevalent digestive system malignancy. Aspirin is currently one of the most promising chemopreventive agents for CRC, and the combination of aspirin and natural compounds helps to enhance the anticancer activity of aspirin. Natural flavonoids like vitexin have an anticancer activity focusing on colorectal carcinoma. This study investigated the potential mechanism of action of the novel combination of vitexin and aspirin against colorectal cancer through network pharmacology, molecular docking, molecular dynamics simulation, and in vitro experiments. The results of network pharmacology suggested that vitexin and aspirin regulate multiple signaling pathways through various target proteins such as NFKB1, PTGS2 (COX-2), MAPK1, MAPK3, and TP53. Cellular experiments revealed that the combined effect of vitexin and aspirin significantly inhibited HT-29 cell growth. Vitexin dose-dependently inhibited COX-2 expression in cells and enhanced the down-regulation of COX-2 and NF-κB expression in colorectal cancer cells by aspirin. This study provides a pharmacodynamic material and theoretical basis for applying agents against colorectal cancer to delay the development of drug resistance and improve the prognosis of cancer patients.

ENTPD1-AS1-miR-144-3p-mediated high expression of COL5A2 correlates with poor prognosis and macrophage infiltration in gastric cancer.

Gastric cancer (GC) is a malignant tumor with high morbidity and mortality. Expression of COL5A2 is significantly elevated in GC. Abnormal expression of noncoding RNAs (ncRNAs) have been found in GC, including microRNA (miRNA) and long noncoding RNA (lncRNA). Competing endogenous RNA network plays an important regulatory role in GC. However, its specific regulatory mechanism has not been elucidated. To gain insight into the ncRNA regulatory mechanism and immune microenvironment related to COL5A2 in GC. RNA sequencing data and clinical information from The Cancer Genome Atlas data portal were used to analyze the expressions of COL5A2, miRNA and lncRNA related to the prognosis of GC. Cox regression analysis and Kyoto Encyclopedia of Genes and Genomes analysis were performed to assess the risk factors and relevant function of COL5A2. StarBase was used to predict the interaction of miRNA-lncRNA or miRNA-mRNA in GC. The relationship between COL5A2, miR-144-3p and ENTPD1-AS1 were verified by dual luciferase reporter assay. The association of COL5A2 with immune cell infiltration were analyzed using the Tumor Immune Estimation Resource database and single sample gene set enrichment analysis. The expression of COL5A2 and macrophages in paired GC tissues were detected by immunohistochemical staining. We verified that the upregulation of COL5A2 expression was associated with the prognosis of GC and was an independent risk factor for GC. miR-144-3p was downregulated and correlated with the prognosis of GC. miR-144-3p regulated the expression of COL5A2 through direct interaction with COL5A2. ENTPD1-AS1 was elevated in GC and competitively bound to miR-144-3p, thus inhibiting the expression of miR-144-3p. ENTPD1-AS1 enhanced the expression of COL5A2 through sponging miR-144-3p. Compared to paired normal tissue, COL5A2 expression was upregulated at the protein level, especially in the middle and late stages of GC. The high expression of COL5A2 was positively linked to macrophage infiltration in GC. COL5A2 regulated by ENTPD1-AS1-miR-144-3p was associated with poor prognosis and macrophage infiltration in GC. This could be a new biomarker and therapeutic target in GC.

Proteomics-based identification of proteins in tumor-derived exosomes as candidate biomarkers for colorectal cancer.

Colorectal cancer (CRC) is the second leading cause of cancer-related death, with high morbidity worldwide. There is an urgent need to find reliable diagnostic biomarkers of CRC and explore the underlying molecular mechanisms. Exosomes are involved in intercellular communication and participate in multiple pathological processes, serving as an important part of the tumor microenvironment. To investigate the proteomic characteristics of CRC tumor-derived exosomes and to identify candidate exosomal protein markers for CRC. In this study, 10 patients over 50 years old who were diagnosed with moderately differentiated adenocarcinoma were recruited. We paired CRC tissues and adjacent normal intestinal tissues (> 5 cm) to form the experimental and control groups. Purified exosomes were extracted separately from each tissue sample. Data-independent acquisition mass spectrometry was implemented in 8 matched samples of exosomes to explore the proteomic expression profiles, and differentially expressed proteins (DEPs) were screened by bioinformatics analysis. Promising exosomal proteins were verified using parallel reaction monitoring (PRM) analysis in 10 matched exosome samples. A total of 1393 proteins were identified in the CRC tissue group, 1304 proteins were identified in the adjacent tissue group, and 283 proteins were significantly differentially expressed between them. Enrichment analysis revealed that DEPs were involved in multiple biological processes related to cytoskeleton construction, cell movement and migration, immune response, tumor growth and telomere metabolism, as well as ECM-receptor interaction, focal adhesion and mTOR signaling pathways. Six differentially expressed exosomal proteins (NHP2, OLFM4, TOP1, SAMP, TAGL and TRIM28) were validated by PRM analysis and evaluated by receiver operating characteristic curve (ROC) analysis. The area under the ROC curve was 0.93, 0.96, 0.97, 0.78, 0.75, and 0.88 (P < 0.05) for NHP2, OLFM4, TOP1, SAMP, TAGL, and TRIM28, respectively, indicating their good ability to distinguish CRC tissues from adjacent intestinal tissues. In our study, comprehensive proteomic profiles were obtained for CRC tissue exosomes. Six exosomal proteins, NHP2, OLFM4, TOP1, SAMP, TAGL and TRIM28, may be promising diagnostic markers and effective therapeutic targets for CRC, but further experimental investigation is needed.

Integrated analysis of single-cell and bulk RNA-seq establishes a novel signature for prediction in gastric cancer.

Single-cell sequencing technology provides the capability to analyze changes in specific cell types during the progression of disease. However, previous single-cell sequencing studies on gastric cancer (GC) have largely focused on immune cells and stromal cells, and further elucidation is required regarding the alterations that occur in gastric epithelial cells during the development of GC. To create a GC prediction model based on single-cell and bulk RNA sequencing (bulk RNA-seq) data. In this study, we conducted a comprehensive analysis by integrating three single-cell RNA sequencing (scRNA-seq) datasets and ten bulk RNA-seq datasets. Our analysis mainly focused on determining cell proportions and identifying differentially expressed genes (DEGs). Specifically, we performed differential expression analysis among epithelial cells in GC tissues and normal gastric tissues (NAGs) and utilized both single-cell and bulk RNA-seq data to establish a prediction model for GC. We further validated the accuracy of the GC prediction model in bulk RNA-seq data. We also used Kaplan-Meier plots to verify the correlation between genes in the prediction model and the prognosis of GC. By analyzing scRNA-seq data from a total of 70707 cells from GC tissue, NAG, and chronic gastric tissue, 10 cell types were identified, and DEGs in GC and normal epithelial cells were screened. After determining the DEGs in GC and normal gastric samples identified by bulk RNA-seq data, a GC predictive classifier was constructed using the Least absolute shrinkage and selection operator (LASSO) and random forest methods. The LASSO classifier showed good performance in both validation and model verification using The Cancer Genome Atlas and Genotype-Tissue Expression (GTEx) datasets [area under the curve (AUC)_min = 0.988, AUC_1se = 0.994], and the random forest model also achieved good results with the validation set (AUC = 0.92). Genes TIMP1, PLOD3, CKS2, TYMP, TNFRSF10B, CPNE1, GDF15, BCAP31, and CLDN7 were identified to have high importance values in multiple GC predictive models, and KM-PLOTTER analysis showed their relevance to GC prognosis, suggesting their potential for use in GC diagnosis and treatment. A predictive classifier was established based on the analysis of RNA-seq data, and the genes in it are expected to serve as auxiliary markers in the clinical diagnosis of GC.

Clinical significance and potential application of cuproptosis-related genes in gastric cancer.

Worldwide, gastric cancer (GC) is a common lethal solid malignancy with a poor prognosis. Cuproptosis is a novel type of cell death mediated by protein lipoylation and may be related to GC prognosis. To offer new insights to predict GC prognosis and provide multiple therapeutic targets related to cuproptosis-related genes (CRGs) for future therapy. We collected data from several public data portals, systematically estimated the expression level and prognostic values of CRGs in GC samples, and investigated related mechanisms using public databases and bioinformatics. Our results revealed that FDX1, LIAS, and MTF1 were differentially expressed in GC samples and exhibited important prognostic significance in The Cancer Genome Atlas (TCGA) cohort. We constructed a nomogram model for overall survival and disease-specific survival prediction and validated it via calibration plots. Mecha-nistically, immune cell infiltration and DNA methylation prominently affected the survival time of GC patients. Moreover, protein-protein interaction network, KEGG pathway and gene ontology enrichment analyses demonstrated that FDX1, LIAS, MTF1 and related proteins play key roles in the tricarboxylic acid cycle and cuproptosis. Gene Expression Omnibus database validation showed that the expression levels of FDX1, LIAS, and MTF1 were consistent with those in the TCGA cohort. Top 10 perturbagens has been filtered by Connectivity Map. In conclusion, FDX1, LIAS, and MTF1 could serve as potential prognostic biomarkers for GC patients and provide novel targets for immunotarget therapy.

Role of ferroptosis in esophageal cancer and corresponding immunotherapy.

Esophageal cancer (EC) is one of the most common digestive system malignancies in the world. The combined modality treatment of EC is usually surgery and radiation therapy, however, its clinical efficacy for advanced patients is relatively limited. Ferroptosis, a new type of iron-dependent programmed cell death, is different from apoptosis, necrosis and autophagy. In recent years, many studies have further enlightened that ferroptosis plays an essential role in the occurrence, development and metastasis of tumors. Targeting ferroptosis stimulates a new direction for further exploration of oncologic treatment regimens. Furthermore, ferroptosis has a critical role in the immune microenvironment of tumors. This paper reviews the mechanism of ferroptosis and the ferroptosis research progress in the treatment of EC. We further elaborate the interaction between ferroptosis and immunotherapy, and the related mechanisms of ferroptosis participation in the immunotherapy of EC, so as to provide new directions and ideas for the treatment of EC.

Comprehensive bioinformatic analysis of mind bomb 1 gene in stomach adenocarcinoma.

The carcinogenesis of stomach adenocarcinoma (STAD) involves many different molecules and multiple pathways, including the NOTCH signaling pathway. As a key factor that functions as a critical link in the NOTCH pathway, mind bomb 1 (MIB1) is upregulated in various tumors and has been reported to promote cell metastasis and invasion. However, studies on the role of MIB1 in STAD are limited. Here, we evaluated the prognostic value of MIB1 in STAD and its association with immune infiltration and copy number variation. To elucidate the relationship between MIB1 gene and gastric cancer (GC) and provide a new idea for the treatment of GC. We identified mutations in the MIB1 gene by searching the cBioPortal database and then analyzed their relationship with the overall survival rate and disease-free survival rate using the Kaplan-Meier method. The Cancer Genome Atlas (TCGA) database provided transcript levels for MIB1 in STADs and normal tissues. As a method of distinguishing the STAD tissues from adjacent normal tissues, a receiver operating characteristic (ROC) curve was generated. Kaplan-Meier plotter was used to determine the effect of MIB1 expression on survival. Based on the LinkedOmics database, we were able to identify the coexpressed genes of the MIB1 gene, the top 50 positively correlated genes, and the top 50 negatively correlated genes. STRING was used to construct protein-protein interaction networks related to the MIB1 gene. An analysis of functional enrichment was carried out using the R package "Cluster Profiler". The relationships between mRNA expression of MIB1 and immune infiltrates were assessed by Tumor IMmune Estimation Resource (TIMER) and the "GSVA package" in R. According to the cBioPortal database, the MIB1 mutation rate in 287 patients in the TCGA dataset was approximately 6%. Kaplan-Meier survival analysis showed that patients with STAD in the mutated group had a worse prognosis than those in the unmutated group (P = 0.0156). There was a significant upregulation of MIB1 expression in STAD tissues compared to adjacent normal tissues. A high T stage was associated with increased MIB1 mRNA expression. The ROC curve analysis revealed 59.4% sensitivity and 85.6% specificity of MIB1 for differentiating STAD tissues from adjacent normal tissues at a truncation level of 2.248. Kaplan-Meier plotter indicated that patients with higher MIB1 levels had a worse prognosis than those with lower levels (26.4 mo vs 56.2 mo, P = 0.0330). A correlation analysis demonstrated an association between immune infiltrates and MIB1 mRNA expression. Upregulation of MIB1 expression is significantly associated with poor survival rate and immune infiltration in gastric adenocarcinoma. MIB1 may be a biomarker for the poor prognosis of STAD patients and a potential immunotherapeutic target.

Efficacy of continuous gastric artery infusion chemotherapy in relieving digestive obstruction in advanced gastric cancer.

Obstruction or fullness after feeding is common in gastric cancer (GC) patients, affecting their nutritional status and quality of life. Patients with digestive obstruction are generally in a more advanced stage. Existing methods, including palliative gastrectomy, gastrojejunostomy, endoluminal stent, jejunal nutrition tube and intravenous chemotherapy, have limitations in treating these symptoms. To analyze the efficacy of continuous gastric artery infusion chemotherapy (cGAIC) in relieving digestive obstruction in patients with advanced GC. This study was a retrospective study. Twenty-nine patients with digestive obstruction of advanced GC who underwent at least one cycle of treatment were reviewed at The Second Affiliated Hospital of Zhejiang University School of Medicine. The oxaliplatin-based intra-arterial infusion regimen was applied in all patients. Mild systemic chemotherapy was used in combination with local treatment. The clinical response was evaluated by contrast-enhanced computed tomography using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Digestive tract symptoms and toxic effects were analyzed regularly. A comparison of the Karnofsky Performance Status (KPS) score and Stooler's Dysphagia Score before and after therapy was made. Univariate survival analysis and multivariate survival analysis were also performed to explore the key factors affecting patient survival. All patients finished cGAIC successfully without microcatheter displacement, as confirmed by arteriography. The median follow-up time was 24 mo (95%CI: 20.24-27.76 mo). The overall response rate was 89.7% after cGAIC according to the RECIST criteria. The postoperative Stooler's Dysphagia Score was significantly improved. Twenty-two (75.9%) of the 29 patients experienced relief of digestive obstruction after the first two cycles, and 13 (44.8%) initially unresectable patients were then considered radically resectable. The median overall survival time (mOS) was 16 mo (95%CI: 9.32-22.68 mo). Patients who received radical surgery had a significantly longer mOS than other patients (P value < 0.001). Multivariate Cox regression analysis indicated that radical resection after cGAIC, intravenous chemotherapy after cGAIC, and immunotherapy after cGAIC were independent predictors of mOS. None of the patients stopped treatment because of adverse events. cGAIC was effective and safe in relieving digestive obstruction in advanced GC, and it could improve surgical conversion possibility and survival time.

Application of G-quadruplex targets in gastrointestinal cancers: Advancements, challenges and prospects.

Genomic instability and inflammation are considered to be two enabling characteristics that support cancer development and progression. G-quadruplex structure is a key element that contributes to genomic instability and inflammation. G-quadruplexes were once regarded as simply an obstacle that can block the transcription of oncogenes. A ligand targeting G-quadruplexes was found to have anticancer activity, making G-quadruplexes potential anticancer targets. However, further investigation has revealed that G-quadruplexes are widely distributed throughout the human genome and have many functions, such as regulating DNA replication, DNA repair, transcription, translation, epigenetics, and inflammatory response. G-quadruplexes play double regulatory roles in transcription and translation. In this review, we focus on G-quadruplexes as novel targets for the treatment of gastrointestinal cancers. We summarize the application basis of G-quadruplexes in gastrointestinal cancers, including their distribution sites, structural characteristics, and physiological functions. We describe the current status of applications for the treatment of esophageal cancer, pancreatic cancer, hepatocellular carcinoma, gastric cancer, colorectal cancer, and gastrointestinal stromal tumors, as well as the associated challenges. Finally, we review the prospective clinical applications of G-quadruplex targets, providing references for targeted treatment strategies in gastrointestinal cancers.

Clinical association between coagulation indicators and bone metastasis in patients with gastric cancer.

Bones are one of the most common target organs for cancer metastasis. Early evaluation of bone metastasis (BM) status is clinically significant. Cancer patients often experience a hypercoagulable state. To evaluate the correlation between coagulation indicators and the burden of BM in gastric cancer (GC). We conducted a single-center retrospective study and enrolled 454 patients. Clinical information including routine blood examination and coagulation markers were collected before any treatment. Patients were grouped according to the status of BM. Receiver operating characteristic curves were used to assess diagnostic performance and determine the optimal cutoff values of the above indicators. Cutoff values, sensitivity and specificity were based on the maximum Youden index. Univariate and multivariate logistic regression analyses were used to evaluate the relationships between biomarkers and BM. Of the 454 enrolled patients, 191 patients were diagnosed with BM. The receiver operating characteristic curve analysis suggested that prothrombin time (PT) [cutoff: 13.25; sensitivity: 0.651; specificity: 0.709; area under receiver operating characteristic curve (AUC) = 0.738], activated partial thromboplastin time (aPTT) (cutoff: 35.15; sensitivity: 0.640; specificity: 0.640; AUC = 0.678) and fibrin degradation products (FDP) (cutoff: 2.75; sensitivity: 0.668; specificity: 0.801; AUC = 0.768) act as novel predictors for BM. Based on multivariate logistic regression analysis, the results showed the independent correlation between PT [odds ratio (OR): 3.16; 95% confidence interval (CI): 1.612-6.194; P = 0.001], aPTT (OR: 2.234; 95%CI: 1.157-4.313; P = 0.017) and FDP (OR: 3.17; 95%CI: 1.637-6.139; P = 0.001) and BM in patients with GC. Moreover, age, carcinoembryonic antigen, erythrocyte and globulin were found to be significantly associated with BM. Coagulation markers, namely PT, aPTT and FDP, might be potential predictors for screening BM in patients with GC.

Efficacy of concurrent chemoradiotherapy with thalidomide and S-1 for esophageal carcinoma and its influence on serum tumor markers.

Although the current conventional treatment strategies for esophageal carcinoma (EC) have been proven effective, they are often accompanied by serious adverse events. Therefore, it is still necessary to continue to explore new therapeutic strategies for EC to improve the clinical outcome of patients. To elucidate the clinical efficacy of concurrent chemoradiotherapy (CCRT) with thalidomide (THAL) and S-1 (tegafur, gimeracil, and oteracil potassium capsules) in the treatment of EC as well as its influence on serum tumor markers (STMs). First, 62 patients with EC treated at the Zibo 148 Hospital between November 2019 and November 2022 were selected and grouped according to the received treatment. Among these, 30 patients undergoing CCRT with cis-platinum and 5-fluorouracil were assigned to the control group (Con), and 32 patients receiving CCRT with THAL and S-1 were assigned to the research group (Res). Second, inter-group comparisons were carried out with respect to curative efficacy, incidence of drug toxicities, STMs [carbohydrate antigen 125 (CA125) and macrophage inflammatory protein-3α (MIP-3α)], angiogenesis-related indicators [vascular endothelial growth factor (VEGF); VEGF receptor-1 (VEGFR-1); basic fibroblast growth factor (bFGF); angiogenin-2 (Ang-2)], and quality of life (QoL) [QoL core 30 (QLQ-C30)] after one month of treatment. The analysis showed no statistical difference in the overall response rate and disease control rate between the two patient cohorts; however, the incidences of grade I-II myelosuppression and gastrointestinal reactions were significantly lower in the Res than in the Con. Besides, the post-treatment CA125, MIP-3α, VEGF, VEGFR-1, bFGF, and Ang-2 Levels in the Res were markedly lower compared with the pre-treatment levels and the corresponding post-treatment levels in the Con. Furthermore, more evident improvements in QLQ-C30 scores from the dimensions of physical, role, emotional, and social functions were determined in the Res. The above results demonstrate the effectiveness of THAL + S-1 CCRT for EC, which contributes to mild side effects and significant reduction of CA125, MIP-3α, VEGF, VEGFR-1, bFGF, and Ang-2 Levels, thus inhibiting tumors from malignant progression and enhancing patients' QoL.

Characterization of pyroptosis-related genes in esophageal cancer and construction of a prognostic model.

Esophageal cancer (EC) is a highly malignant digestive system tumor that often lacks evident early symptoms and has a poor prognosis. Pyroptosis, a form of programmed cell death, has been shown to be associated with the occurrence and progression of many malignancies. However, its role in esophageal cancer remains unclear. This work aimed to evaluate the prognostic value of pyroptosis-related genes (PRGs) in EC using data from The Cancer Genome Atlas (TCGA) cohort. The RNA-seq data from 171 esophageal samples in the TCGA database were employed. Differential expression genes (DEGs) between tumor and non-tumor samples were compared. Protein-protein interaction (PPI) networks were constructed using the STRING database, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and Gene Ontology (GO) analyses were performed using the "clusterProfiler" package in R. Furthermore, based on the DEGs, all esophageal cancer cases were classified into three subtypes. A risk model for gene features was established using the LASSO regression method, and EC patients in the TCGA cohort were divided into high-risk and low-risk groups. A total of 614 PRGs were identified. Among them, 32 DEGs (31 upregulated and 1 downregulated) were found between normal esophageal tissue and EC tissue. PPI analysis identified key genes including IL-1β, CASP1, AIM2, HMGB1, GSDMD, PYCARD, IL-18, BAK1, and TP53. On the other hand, the low-risk group exhibited a significantly higher survival rate than the high-risk group (p < 0.001). Combined with the clinical characteristics of the TCGA cohort, it was found that the risk score was an independent prognostic factor for overall survival (OS) prediction in EC patients. KEGG and GO analyses revealed the enrichment of genes associated with cell proliferation in the high-risk group. PRGs play a crucial role in the occurrence and development of EC and can be used to predict the prognosis of EC patients.

A comprehensive evaluation of serum tRF-29-R9J8909NF5JP as a novel diagnostic and prognostic biomarker for gastric cancer.

Gastric cancer (GC) is a common malignant digestive system tumor. Since the early symptoms of GC are usually vague and the positive rate of common biomarkers of GC is low, it is of urgent need to find new biomarkers with good sensitivity and specificity to screen and diagnose GC patients. The tRNA-derived small RNAs (tsRNAs) are emerging small noncoding RNAs that play an essential role in cancer progression. In this study, we explored whether novel tsRNAs have the potential to serve as biomarkers for GC. Three tsRNAs significantly upregulated in GC were screened by the tsRFun database. The expression level of tRF-29-R9J8909NF5JP was detected by real-time fluorescence quantitative polymerase chain reaction. Agarose gel electrophoresis and Sanger sequencing were used to verify the characteristics of tRF-29-R9J8909NF5JP. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of tRF-29-R9J8909NF5JP. The χ2 test was used to analyze the correlation between tRF-29-R9J8909NF5JP expression level and clinicopathological parameters. Kaplan-Meier survival curves were used to analyze the correlation between tRF-29-R9J8909NF5JP expression levels and survival time of GC patients. In this study, the expression level of tRF-29-R9J8909NF5JP was significantly increased in GC tissues. The expression level of tRF-29-R9J8909NF5JP was considerably higher in the serum of GC patients than in the serum of gastritis patients and in the serum of healthy donors, and the expression level of tRF-29-R9J8909NF5JP was significantly decreased in the serum of GC patients after surgery. In addition, the χ2 test showed that the expression level of tRF-29-R9J8909NF5JP in GC serum was correlated with differentiation grade, T-stage, lymph node metastasis, tumor node metastasis stage, and neurological/vascular invasion. The results of the survival curve showed that the high expression of serum tRF-29-R9J8909NF5JP was associated with a low survival rate. ROC analysis showed that serum tRF-29-R9J8909NF5JP had higher diagnostic efficiency than common GC biomarkers, and the diagnostic efficiency was further improved by combining them. At the end of the study, we predicted the downstream of tRF-29-R9J8909NF5JP. The expression level of tRF-29-R9J8909NF5JP in the serum of GC patients can effectively identify GC patients and has higher efficacy than conventional biomarkers. In addition, serum tRF-29-R9J8909NF5JP can monitor the postoperative condition of GC patients, suggesting that it has the potential to become a biomarker for GC.

Malignancy in dermatomyositis: a mono-centric retrospective study of 134 patients in China and a potential predictive model.

To describe the demographics and phenotypes of malignancies-associated dermatomyositis (MADM) in east China and pinpoint potential factors indicative of malignancies in patients with dermatomyositis and establish a predictive model. We retrospectively analyzed clinical data from 134 patients with adult-onset dermatomyositis hospitalized between January 2019 and May 2022 in one comprehensive hospital. Clinical data including disease course, initial symptoms and signs, and demographic information were retrieved from the Electronic Medical Records System. Other parameters including myositis-specific autoantibodies profiles, ferritin, sedimentation, etc. were all referable. Multivariable multinomial logistic regression was employed to simulate a model to predict cancer risks. Receiver operating characteristic curve was adopted to evaluate the potency of the model. 134 patients with adult-onset dermatomyositis were aptly enrolled in this study based on inclusive and exclusive criteria: 12 (8.96%) with malignancies, 57 (42.53%) with aberrant tumor biomarkers but no malignancies, 65 (48.51%) with neither malignancies nor abnormal tumor biomarkers. Senior diagnostic age, higher LDH, higher ferritin, positive anti-TIF1γ and anti-Mi2 rather than anti-NXP2 autoantibodies were positive indicators of malignancies. Additionally, neither initial complaints nor signs were found to be correlated to a tendency towards malignancies. Digestive system, nasopharyngeal, and lung malignancies were mostly documented in east China. One multivariable multinomial logistic regression model was established to predict the phenotypes of dermatomyositis on the basis of potential malignancies and the overall sensitivity and specificity was satisfactory. Positivity of anti-TIF1γ and anti-Mi2 autoantibodies are highly indicative of malignancies while the role of anti-NXP2 autoantibody in MADM in the Chinese population remains unclear. The phenotypes of malignancies can be predicted through the model and the predictive power is sufficient. More attention should be paid to malignancies screening in patients with aberrant tumor biomarkers but no malignancies, particularly digestive system, nasopharyngeal, and lung malignancies in patients with dermatomyositis but without malignancies.

The Diagnostic Value of Circulating miR-29 Family for Digestive System Malignancies: A Meta-Analysis.

To evaluate the diagnostic value of circulating microRNA-29 (miR-29) in digestive system malignant neoplasms by meta-analysis. We searched the PubMed, Embase, Cochrane Library, and Web of Science to collect studies, published through September 2022, on the diagnostic value of miR-29 in digestive system tumors. We included 7 studies in this meta-analysis, including colorectal cancer, esophageal squamous cell carcinomas, and cholangiocarcinoma. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.64 (95% CI, 0.53-0.74), 0.83 (0.60-0.94), 3.75 (1.42-9.91), 0.44 (0.31-0.61), and 8.63 (2.54-29.26), respectively. The area under the summary receiver operating characteristic curve was 0.75. The sensitivity of miR-29 derived from serum was higher than that of miR-29 derived from plasma for malignant digestive system tumors (0.71 vs 0.54; P = .04). This meta-analysis suggests that the circulating miR-29 family has good diagnostic performance for digestive system malignant tumors, with moderate sensitivity and good specificity.

Clinical characteristics and prognostic nomogram analysis of patients with dual primary cancers with first gastric cancer: a retrospective study in China.

With the improvement in diagnosis and treatment of gastric cancer (GC), the survival time of patients has been gradually prolonged. However, these survivors are at increased risk for other diseases, including second primary cancers (SPCs). Currently, there remain few central studies concerning double primary cancers with first gastric cancer (DPCFGC). Thus, this study aimed to investigate these patients' clinical characteristics and perform prognostic nomogram analysis. The clinical data of 78 DPCFGC patients were retrospectively collected and analyzed through the hospital electronic medical record system. Univariate and multivariate Cox regression analyses were performed to screen independent risk factors, based on which the prognostic nomogram was further constructed and validated using the R software package. Finally, Kaplan-Meier curves were plotted to explore the association of overall survival (OS) with prognostic factors and the model. The prevalence of DPCFGC was 0.86%, of which the proportions of synchronous and metachronous patients were 47.44% and 52.56% , respectively; 65.38% (51/78) and 34.62% (27/78) of patients were male and female, respectively. The median age at GC and SPC diagnosis was 63 and 65 years, respectively, and 52.57% of GC patients developed SPCs within 1 year. The top three SPCs were in the esophagus (19.24%), colon (16.67%), and rectum (15.39%). The most common features of GC and SPCs were adenocarcinoma, poorly and moderately differentiated histology, and pathological stages I and II. The radical resection rate of GC was significantly lower in synchronous patients than in metachronous patients (45.94% vs. 100.00%, P < 0.001), but no significant difference was noted in the radical resection rate of SPCs (35.13% vs. 46.34%, P = 0.315). The OS of DPCFGC patients was 31.03 ± 4.14 months. The pathological stage of GC and SPCs, whether to operate for GC, and diagnostic interval were independent risk factors. The predictive efficacy of the prognostic nomogram for 1-, 2- and 3-year OS in DPCFGC patients was 0.922, 0.935 and 0.796 , respectively, with good consistency and clinical applicability. The OS was significantly lower in the high-risk group than in the low-risk group. During follow-up, clinicians should attach great importance to the screening of GC survivors, especially at early stage in older men within 1 year after diagnosis, and be alert to the possibility of occurrent digestive system malignancies. The nomogram constructed in this study can provide a theoretical basis for the early clinical development of individualized treatment plans.

Magnetic resonance/fluorescence dual-modality contrast agents targeting αvβ6-overexpressing tumors based on A20FMDV2 peptide as a ligand

Pancreatic ductal adenocarcinoma (PDAC) is a malignant digestive system tumor with a poor late-stage prognosis. This study aimed to identify new methods for the early detection of PDAC. The nanoprobe A20FMDV2-Gd-5-FAM was developed using A20FMDV2 (N1AVPNLRGDLQVLAQKVART20-NH2, A20FMDV2) as the ligand and characterized using dynamic light scattering, transmission electron microscopy, Fourier transform infrared analysis, and UV absorption spectroscopy. The binding of pancreatic cancer cells AsPC-1, MIA PaCa-2, and normal human pancreatic H6C7 cells (HPDE6-C7) to the probe was verified using laser confocal microscopy, and the biocompatibility of the probe was evaluated in vivo. In vivo magnetic resonance and fluorescence imaging were also performed on nude mice with subcutaneous pancreatic tumor xenografts to verify the bimodal imaging performance of the probe. The probe exhibited good stability and biocompatibility and an enhanced relaxation rate (25.46 ± 1.32 mM−1 s−1) than Gd-DTPA. Confocal laser scanning microscopy results revealed that the A20FMDV2-Gd-5-FAM probe could be successfully ingested and internalized, and infrared analysis results demonstrated that the probe was linked successfully. Finally, magnetic resonance T1WI imaging and intravital fluorescence imaging demonstrated the specific signal enhancement of the probe at the tumor site. In conclusion, the bimodal molecular probe A20FMDV2-Gd-5-FAM showed a stable magnetic resonance and fluorescence bimodal imaging performance and is a promising new approach for diagnosing early-stage cancers with a high integrin αvβ6 expression.

Characteristics of malignant tumors of digestive system and autoimmune diseases.

With the development of preoperative examination technology, endoscopic ultrasonography-guided fine-needle aspiration biopsy (EUS-FNA) has been widely used in preoperative pathological diagnosis. However, challenges remain in obtaining appropriate tissue samples and obtaining accurate pathological results to predict disease risk. Therefore, this study aimed to analyze the characteristics of digestive system malignancies and their autoimmune diseases, and to analyze the clinicopathological features, preoperative CT imaging features and pathological grades of pNENs of different pathological degrees of pNENs on the prognosis of pNENs. Experimental results showed that non-functioning pancreatic neuroendocrine tumors showed prominent surrounding hypervascular lesions on multiphase CT examination. Among them, arterial phase and portal venous phase were most clearly imaged at the end, and the degree of local vascular invasion could be used as an index to evaluate its resectability. The sensitivity of CT examination was 63% to 82%, and the specificity was 83% to 100%, depending on the size.

Prevention of malignant digestive system tumors should focus on the control of chronic inflammation.

Chronic inflammation, through a variety of mechanisms, plays a key role in the occurrence and development of digestive system malignant tumors (DSMTs). In this study, we feature and provide a comprehensive understanding of DSMT prevention strategies based on preventing or controlling chronic inflammation. The development and evaluation of cancer prevention strategies is a longstanding process. Cancer prevention, especially in the early stage of life, should be emphasized throughout the whole life course. Issues such as the time interval for colon cancer screening, the development of direct-acting antiviral drugs for liver cancer, and the Helicobacter pylori vaccine all need to be explored in long-term, large-scale experiments in the future.