Biomarker For Gastric Cancer Research Articles

ABCC2 induces metabolic vulnerability and cellular ferroptosis via enhanced glutathione efflux in gastric cancer.

Although it is traditionally believed that ATP binding cassette subfamily C member 2 (ABCC2) is a multidrug resistance-associated protein correlated with a worse prognosis, our previous and several other studies demonstrated the contrary to be true in gastric cancer (GC). We aim to explore the underlying mechanism of this discovery. Our study utilized whole-exome sequencing (WES), RNA sequencing, and droplet digital PCR (ddPCR) analysis of 80 gastric cancer samples, along with comprehensive immunohistochemical (IHC) analysis of 1044 human GC tissue samples.By utilizing CRISPRCas9 to genetically modify cell lines with the ABCC2-24C > T (rs717620) point mutation and conducting dual-luciferase reporter assays, we identified that transcription factors SOX9 and ETS1 serve as negative regulators of ABCC2 expression. Seahorse assay and mass spectrometry were used to discover altered metabolic patterns. Gain and loss-of-function experiments in GC cell lines and preclinical models were carried out to validate ABCC2 biological function. ABCC2 high expression correlated with better prognosis, and rs717620 can influence ABCC2 expression by disrupting the binding of ETS1 and SOX9. Gain and loss-of-function experiments in GC cell lines demonstrated amino acid deprivation reduces proliferation, migration, and drug resistance in ABCC2-high GC cells. ABCC2 leads to reduced intracellular amino acid pools and disruption of cellular energy metabolism. This phenomenon depended on ABCC2-mediated GSH extrusion, resulting in alterations in redox status, thereby increasing the cell's susceptibility to ferroptosis. Furthermore, patient-derived organoids and patient-derived tumor-like cell clusters were used to observe impact of ABCC2 on therapeutic effect. In the xenograft model with high ABCC2 expression, we observed that constricting amino acid intake in conjunction with GPX4 inactivation resulted in notable tumor regression. Our findings demonstrate a significant role of ABCC2 in amino acid metabolism and ferroptosis by mediating GSH efflux in GC. This discovery underlines the potential of combining multiple ferroptosis targets as a promising therapeutic strategy for GC with high ABCC2 expression. ABCC2 plays a crucial role in inducing metabolic vulnerability and ferroptosis in gastric cancer through enhanced glutathione efflux. The ABCC2 24C > T polymorphism is a key factor influencing its expression. These results highlight the potential of ABCC2 as a predictive biomarker and therapeutic target in gastric cancer.

Screening of gastric cancer diagnostic biomarkers in the homologous recombination signaling pathway and assessment of their clinical and radiomic correlations.

Homologous recombination plays a vital role in the occurrence and drug resistance of gastric cancer. This study aimed to screen new gastric cancer diagnostic biomarkers in the homologous recombination pathway and then used radiomic features to construct a prediction model of biomarker expression to guide the selection of chemotherapy regimens. Gastric cancer transcriptome data were downloaded from The Cancer Genome Atlas database. Machine learning methods were used to screen for diagnostic biomarkers of gastric cancer and validate them experimentally. Computed Tomography image data of gastric cancer patients and corresponding clinical data were downloaded from The Cancer Imaging Archive and our imaging centre, and then the Computed Tomography images were subjected to feature extraction, and biomarker expression prediction models were constructed to analyze the correlation between the biomarker radiomics scores and clinicopathological features. We screened RAD51D and XRCC2 in the homologous recombination pathway as biomarkers for gastric cancer diagnosis by machine learning, and the expression of RAD51D and XRCC2 was significantly positively correlated with pathological T stage, N stage, and TNM stage. Homologous recombination pathway blockade inhibits gastric cancer cell proliferation, promotes apoptosis, and reduces the sensitivity of gastric cancer cells to chemotherapeutic drugs. Our predictive RAD51D and XRCC2 expression models were constructed using radiomics features, and all the models had high accuracy. In the external validation cohort, the predictive models still had decent accuracy. Moreover, the radiomics scores of RAD51D and XRCC2 were also significantly positively correlated with the pathologic T, N, and TNM stages. The gastric cancer diagnostic biomarkers RAD51D and XRCC2 that we screened can, to a certain extent, reflect the expression status of genes through radiomic characteristics, which is of certain significance in guiding the selection of chemotherapy regimens for gastric cancer patients.

Immune infiltration and prognosis in gastric cancer: role of NAD+ metabolism-related markers.

This study endeavored to develop a nicotinamide adenine dinucleotide (NAD+) metabolism-related biomarkers in gastric cancer (GC), which could provide a theoretical foundation for prognosis and therapy of GC patients. In this study, differentially expressed genes (DEGs1) between GC and paraneoplastic tissues were overlapped with NAD+ metabolism-related genes (NMRGs) to identify differentially expressed NMRGs (DE-NMRGs). Then, GC patients were divided into high and low score groups by gene set variation analysis (GSVA) algorithm for differential expression analysis to obtain DEGs2, which was overlapped with DEGs1 for identification of intersection genes. These genes were further analyzed using univariate Cox and least absolute shrinkage and selection operator (LASSO) regression analyses to obtain prognostic genes for constructing a risk model. Enrichment and immune infiltration analyses further investigated investigate the different risk groups, and qRT-PCR validated the prognostic genes. Initially, we identified DE-NMRGs involved in NAD biosynthesis, with seven (DNAJB13, CST2, THPO, CIDEA, ONECUT1, UPK1B and SNCG) showing prognostic significance in GC. Subsequent, a prognostic model was constructed in which the risk score, derived from the expression profiles of these genes, along with gender, emerged as robust independent predictors of patient outcomes in GC. Enrichment analysis linked high-risk patients to synaptic membrane pathways and low-risk to the CMG complex pathway. Tumor immune infiltration analysis revealed correlations between risk scores and immune cell abundance, suggesting a relationship between NAD+ metabolism and immune response in GC. The prognostic significance of our identified genes was validated by qRT-PCR, which confirmed their upregulated expression in GC tissue samples. In this study, seven NAD+ metabolism-related markers were established, which is of great significance for the development of prognostic molecular biomarkers and clinical prognosis prediction for gastric cancer patients.

HIGD1B, as a novel prognostic biomarker, is involved in regulating the tumor microenvironment and immune cell infiltration; its overexpression leads to poor prognosis in gastric cancer patients.

HIGD1B (HIG1 Hypoxia Inducible Domain Family Member 1B) is a protein-coding gene linked to the occurrence and progression of various illnesses. However, its precise function in gastric cancer (GC) remains unclear. The expression of HIGD1B is determined through the TCGA and GEO databases and verified using experiments. The association between HIGD1B and GC patients' prognosis was analyzed via the Kaplan-Meier (K-M) curve. Subsequently, the researchers utilized ROC curves to assess the diagnostic capacity of HIGD1B and employed COX analysis to investigate risk factors for GC. The differentially expressed genes (DEGs) were then subjected to functional enrichment analysis, and a nomogram was generated to forecast the survival outcome and probability of GC patients. Additionally, we evaluated the interaction between HIGD1B and the immune cell infiltration and predicted the susceptibility of GC patients to therapy. HIGD1B is markedly elevated in GC tissue and cell lines, and patients with high HIGD1B expression have a poorer outcome. In addition, HIGD1B is related to distinct grades, stages, and T stages. The survival ROC curves of HIGD1B and nomogram for five years were 0.741 and 0.735, suggesting appropriate levels of diagnostic efficacy. According to Cox regression analysis, HIGD1B represents a separate risk factor for the prognosis of gastric cancer (p<0.01). GSEA analysis demonstrated that the HIGD1B is closely related to cancer formation and advanced pathways. Moreover, patients with high HIGD1B expression exhibited a higher level of Tumor-infiltration immune cells (TIICs) and were more likely to experience immune escape and drug resistance after chemotherapy and immunotherapy. This study explored the potential mechanisms and diagnostic and prognostic utility of HIGD1B in GC, as well as identified HIGD1B as a valuable biomarker and possible therapeutic target for GC.

Construction and validation of a TTN mutation associated immune prognostic model for evaluating immune microenvironment and outcomes of gastric cancer: An observational study.

Gastric cancer (GC) is a prevalent form of cancer worldwide, and TTN (titin) mutations are frequently observed in GC. However, the association between TTN mutations and immunotherapy for GC remains unclear, necessitating the development of novel prognostic models. The prognostic value and potential mechanisms of TTN in stomach adenocarcinoma were evaluated by TCGA (The Cancer Genome Atlas)-stomach adenocarcinoma cohort analysis, and an immune prognostic model was constructed based on TTN status. We validated it using the GSE84433 dataset. We performed Gene Set Enrichment Analysis and screened for differentially expressed genes, and used lasso (least absolute shrinkage and selection operator) regression analysis to screen for survival genes to construct a multifactorial survival model. In addition, we evaluated the relative proportions of 22 immune cells using the CIBERSORT algorithm for immunogenicity analysis. Finally, we constructed the nomogram integrating immune prognostic model and other clinical factors. GESA showed enrichment of immune-related phenotypes in patients with TTN mutations. We constructed an immune prognostic model based on 16 genes could identify gastric cancer patients with higher risk of poor prognosis. Immuno-microenvironmental analysis showed increased infiltration of naive B cells, plasma cells, and monocyte in high-risk patients. In addition, Nomo plots predicted the probability of 1-year, 3-year, and 5-year OS (overall survival) in GC patients, showing good predictive performance. In this study, we identified that TTN gene may be a potential clinical biomarker for GC and TTN mutations may be a predictor of immunotherapy in patients. We constructed and validated a new model for prognosis of GC patients based on immune characteristics associated with TTN mutations. This study may provide potential therapeutic strategies for gastric cancer.

N6-methyladenosine modified circPAK2 promotes lymph node metastasis via targeting IGF2BPs/VEGFA signaling in gastric cancer.

Circular RNAs (circRNAs) have emerged as key regulators of cancer occurrence and progression, as well as promising biomarkers for cancer diagnosis and prognosis. However, the potential mechanisms of circRNAs implicated in lymph node (LN) metastasis of gastric cancer remain unclear. Herein, we identify a novel N6-methyladenosine (m6A) modified circRNA, circPAK2, which is significantly upregulated in gastric cancer tissues and metastatic LN tissues. Functionally, circPAK2 enhances the migration, invasion, lymphangiogenesis, angiogenesis, epithelial-mesenchymal transition (EMT), and metastasis of gastric cancer in vitro and in vivo. Mechanistically, circPAK2 is exported by YTH domain-containing protein 1 (YTHDC1) from the nucleus to the cytoplasm in an m6A methylation-dependent manner. Moreover, increased cytoplasmic circPAK2 interacts with Insulin-Like Growth Factor 2 mRNA-Binding Proteins (IGF2BPs) and forms a circPAK2/IGF2BPs/VEGFA complex to stabilize VEGFA mRNA, which contributes to gastric cancer vasculature formation and aggressiveness. Clinically, high circPAK2 expression is positively associated with LN metastasis and poor prognosis in gastric cancer. This study highlights m6A-modified circPAK2 as a key regulator of LN metastasis of gastric cancer, thus supporting circPAK2 as a promising therapeutic target and prognostic biomarker for gastric cancer.

Comprehensive landscape of integrator complex subunits and their association with prognosis and tumor microenvironment in gastric cancer.

The integrator complex (INT) is a multiprotein assembly in gene transcription. Although several subunits of INT complex have been implicated in multiple cancers, the complex's role in gastric cancer (GC) is poorly understood. The gene expressions, prognostic values, and the associations with microsatellite instability (MSI) of INT subunits were confirmed by GEO and The Cancer Genome Atlas (TCGA) databases. cBioPortal, GeneMANIA, TISIDB, and MCPcounter algorithm were adopted to investigate the mutation frequency, protein-protein interaction network, and the association with immune cells of INT subunits in GC. Additionally, in vitro experiments were performed to confirm the role of INTS11 in pathogenesis of GC. The mRNA expression levels of INTS2/4/5/7/8/9/10/11/12/13/14 were significantly elevated both in GSE183904 and TCGA datasets. Through functional enrichment analysis, the functions of INT subunits were mainly associated with snRNA processing, INT, and DNA-directed 5'-3' RNA polymerase activity. Moreover, these INT subunit expressions were associated with tumor-infiltrating lymphocytes and MSI in GC. In vitro experiments demonstrated that knockdown of the catalytic core INTS11 in GC cells inhibits cell proliferation ability. INTS11 overexpression showed opposite effects. Our data demonstrate that the INT complex might act as an oncogene and can be used as a prognosis biomarker for GC.

Salivary metabolomic biomarkers for esophageal and gastric cancers by liquid chromatography-mass spectrometry.

Early detection of esophageal and gastric cancers is essential for patients' prognosis; however, optimal noninvasive screening tests are currently not available. Saliva is a biofluid that is readily available, allowing for frequent screening tests. Thus, we explored salivary diagnostic biomarkers for esophageal and gastric cancers using metabolomic analyses. Saliva samples were collected from patients with esophageal (n = 50) and gastric cancer (n = 63), and patients without cancer as controls (n = 20). Salivary metabolites were analyzed by liquid chromatography-mass spectrometry to identify salivary biomarkers. We also examined the metabolic profiles of gastric cancer tissues and compared them with the salivary biomarkers. The sensitivity of the diagnostic models based on salivary biomarkers was assessed by comparing it with that of serum tumor markers. Additionally, using postoperative saliva samples collected from patients with gastric cancer, we analyzed the changes in the biomarkers' concentrations before and after surgery. Cytosine was detected as a salivary biomarker for gastric cancer, and cytosine, 2-oxoglutarate, and arginine were detected as salivary biomarkers for esophageal cancer. Cytidine, a cytosine nucleotide, showed decreased concentrations in gastric cancer tissues. The sensitivity of the diagnostic models for esophageal and gastric cancers was 66.0% and 47.6%, respectively, while that of serum tumor markers was 40%. Salivary cytosine concentration increased significantly postoperatively relative to the preoperative value. In summary, we identified salivary biomarkers for esophageal and gastric cancers, which showed diagnostic sensitivity at least comparable to that of serum tumor markers. Salivary metabolomic tests could be promising screening tests for these types of cancer.

Combined detection of serum EFNA1 and MMP13 as diagnostic biomarker for gastric cancer

We previously identified that serum EFNA1 and MMP13 were potential biomarker for early detection of esophageal squamous cell carcinoma. In this study, our aim is to explore the diagnostic value of serum EFNA1 and MMP13 for gastric cancer. We used enzyme-linked immunosorbent assay (ELISA) to detect the expression levels of serum EFNA1 and MMP13 in 210 GCs and 223 normal controls. The diagnostic value of EFNA1 and MMP13 was evaluated in an independent cohorts of GC patients and normal controls (n = 238 and 195, respectively). Receiver operating characteristics were used to calculate diagnostic accuracy. In training and validation cohorts, serum EFNA1 and MMP13 levels in the GC groups were significantly higher than those in the normal controls (P < 0.001). The area under the curve (AUC) of the combined detection of serum EFNA1 and MMP13 for GC was improved (0.794), compared with single biomarker used. Similar results were observed in the validation cohort. Importantly, the combined measurement of serum EFNA1 and MMP13 to detect early-stage GC also had acceptable diagnostic accuracy in training and validation cohort. Combined detection of serum EFNA1 and MMP13 could help identify early-stage GC, suggesting that it may be a promising tool for the early detection of GC.

Comprehensive multiomics analysis of the signatures of gastric mucosal bacteria and plasma metabolites across different stomach microhabitats in the development of gastric cancer.

As an important component of the microenvironment, the gastric microbiota and its metabolites are associated with tumour occurrence, progression, and metastasis. However, the relationship between the gastric microbiota and the development of gastric cancer is unclear. The present study investigated the role of the gastric mucosa microbiome and metabolites as aetiological factors in gastric carcinogenesis. Gastric biopsies from different stomach microhabitats (n = 70) were subjected to 16S rRNA gene sequencing, and blood samples (n = 95) were subjected to untargeted metabolome (gas chromatography‒mass spectrometry, GC‒MS) analyses. The datasets were analysed using various bioinformatics approaches. The microbiota diversity and community composition markedly changed during gastric carcinogenesis. High Helicobacter. pylori colonization modified the overall diversity and composition of the microbiota associated with gastritis and cancer in the stomach. Most importantly, analysis of the functional features of the microbiota revealed that nitrate reductase genes were significantly enriched in the tumoral microbiota, while urease-producing genes were significantly enriched in the microbiota of H. pylori-positive patients. A panel of 81 metabolites was constructed to discriminate gastric cancer patients from gastritis patients, and a panel of 15 metabolites was constructed to discriminate H. pylori-positive patients from H. pylori-negative patients. receiver operator characteristic (ROC) curve analysis identified a series of gastric microbes and plasma metabolites as potential biomarkers of gastric cancer. The present study identified a series of signatures that may play important roles in gastric carcinogenesis and have the potential to be used as biomarkers for diagnosis and for the surveillance of gastric cancer patients with minimal invasiveness.

Micro gas chromatography column using ionic liquid modified metal-organic framework as stationary phase for rapid breath analysis of gastric cancer

The micro gas chromatography columns (μGCs) were prepared for rapid breath analysis of gastric cancer. The synergistic effect of the specific surface area and the action of pore diameter on the separation capacity was investigated. The μGC-IL/UIO-66 was prepared using [P66614][Cl]/UIO-66 as the stationary phase. For comparison, the μGC-IL and the μGC-UIO-66 were prepared using [P66614][Cl] and UIO-66 as stationary phase, respectively. [P66614][Cl]/UIO-66 had a high specific surface area with a pore diameter distribution of 0.49 nm. The high specific surface area of [P66614][Cl]/UIO-66 improved the efficiency of adsorption and desorption, while the porous structure with an appropriate pore diameter acted as an efficient molecular sieve, synergistically enhancing separation efficiency. So compared to the μGC-IL and the μGC-UIO-66, the HETP of μGC-IL/UIO-66 was reduced by 68.2% and 22.6%, respectively. In the analysis of volatile biomarkers (acetone, benzene, n-hexane and toluene) for gastric cancer, the resolutions between adjacent peaks were 1.96, 2.13 and 3.67, which met the requirements for quantitative analysis (R > 1.5). The retention times of acetone, benzene, n-hexane and toluene were 0.72 min, 0.96 min, 1.33 min and 1.67 min, which enables rapid analysis. All may suggest that the μGC-IL/UIO-66 has a promising application in rapid breath analysis of gastric cancer.

Potential diagnostic, prognostic, and predictive biomarkers of gastric cancer.

Gastric cancer (GC), a malignant epithelial tumor, is the fourth leading cause of cancer-related death worldwide. Therapeutic strategies for GC, despite the biggest challenges, can significantly improve survival rates through early detection and effective screening methods. To provide brief information on the necessity of multiple specific diagnostic, prognostic, and predictive markers for GC. This review was conducted using a variety of search engines, including PubMed Central, Scopus, Web of Science, Google Scholar, and others. Some potential biomarkers that provide essential information include circulating tumor cells (CTCs), DNA methylation, claudin 18.2, fibroblast growth factor receptor 2 (FGFR2), long noncoding RNAs (lncRNAs), cell-free DNA (cfDNA), microRNAs, and serum pepsinogens. Multiple tumor markers are essential for screening, tumor identification, staging, prognostic assessment, and monitoring recurrence after therapy due to the absence of a single tumor indicator for diagnosing, prognosticating, and predicting GC.

Delineating protein biomarkers for gastric cancers: A catalogue of mass spectrometry-based markers and assessment of their suitability for targeted proteomics applications

Gastric cancer (GC) is a global health concern. To facilitate improved management of GCs, protein biomarkers have been identified through mass spectrometry-based proteomics platforms. In order to exhibit clinical utility of such data, we congregated over 6800 differentially regulated proteins in GCs from proteomics studies and recorded the mass spectrometry platforms, association of the protein with infectious agents, protein identifiers, sample size and clinical characters of samples used with details on validation. Development of targeted proteomics methods is the cornerstone for pursuing these markers into clinical utility. Therefore, we developed Protein Biomarker Matrix for Gastric Cancer (PBMGC), a simple catalogue of robustness of each protein. This analysis yielded the identification of robust tissue, serum, and urine diagnostic and prognostic protein biomarker panels which can be further tested for their clinical utility. We also ascertained proteotypic tryptic peptides of 5631 proteins suitable for developing multiple reaction monitoring (MRM) assays. Extensive characterization of these peptides was carried out to record peptide ions, mass/charge and enhanced specific peptide features. With the vision of catering to proteomics researchers, the data generated through this analysis has been catalogued at Gastric Cancer Proteomics DataBase (GCPDB) (https://ciods.in/gcpdb/). Users can browse and download the data and improve GCPDB by submitting recently published data. SignificanceMass spectrometry-based proteomics platforms have accumulated substantial data on proteins differentially regulated in gastric cancer (GC) clinical samples. The utility of such data in clinical applications is limited by search for suitable biomarker panels for assessment of GCs.We assembled over 6800 differentially regulated proteins in GCs from proteomics studies and recorded the corresponding details including mass spectrometry platforms, status on the association of the protein with infectious agents, protein identifiers from different databases, sample size and clinical characters of samples used in test and control conditions along with details on their validation.Towards the vision of utilizing these markers in clinical assays, Protein Biomarker Matrix for Gastric Cancer (PBMGC) was developed and clinically relevant multi-protein panels were identified. We also demonstrated identification and characterization of tryptic proteotypic tryptic peptides of 5631 proteins biomarkers of GCs which are suitable for development of MRM assays in a SCIEX QTRAP instrument.Aimed to caterproteomics researchers, the data generated through this analysis has been catalogued at Gastric Cancer Proteomics DataBase (GCPDB) (https://ciods.in/gcpdb/). The users can browse and download details on different markers and improve GCPDB by submitting recently published data.Such an analysis could lay a cornerstone for building more such resources or conduct such analysis in different clinical conditions to uptake and develop targeted proteomics as the method of choice for clinical applications.

Evaluation of soluble co‐inhibitors and co‐stimulators levels of the immune response in gastric cancer

AbstractBackgroundCo‐inhibitor and co‐stimulator mediators trigger actions that result in immunological homeostasis and are being evaluated as potential therapeutic targets in gastric cancer (GC).ObjectiveTo evaluate the soluble levels of sPD‐1, sPD‐L1, sPD‐L2, sTIM‐3, sGal9, sGITR, and sGITRL in GC patients.MethodsThe cross‐sectional study was carried out at the Hospital de Cancer de Pernambuco, Brazil between 2017 and 2018. A total of 74 GC patients and 30 healthy controls were included.ResultsLow levels of sPD1 (p = 0.0179), sPDL2 (p = 0.0003), and sGal9 (p &lt; 0.0001), and higher levels of sPDL1 (p = 0.004), sTIM‐3 (p = 0.0072), sGITR (p = 0.0179), and sGITRL (p = 0.0055) compared to the control group. High sPD‐1, sTIM‐3, and sGal9 levels in stage IV compared I/II and III (p &lt; 0.05). High sPDL1, sGal9, and sGITRL levels in esophagogastric junction compared to body and Pylorus/Antrum groups (p &lt; 0.05). No significant differences were observed in sPD1, sPDL1, sPDL2, sTIM3, sGal9, sGITR, and sGITRL levels between the intestinal, diffuse, and mixed GC groups. Low sGITR levels in GC patients who died within the first 24 months compared to the who survived (p = 0.0332).ConclusionsThere is an association of sPD1, sTIM‐3, and sGal9 with disease progression and sGITR with death, these mediators may be potential prognostic biomarkers in GC.

Combination Of Lymphocyte Count and Albumin Concentration As A New Prognostic Biomarker For Gastric Cancer

Aim This research links systemic inflammation and nutritional status with gastric cancer prognosis and postoperative outcomes. Methods Patients undergoing total gastrectomy for gastric adenocarcinoma (2015-2018) were categorized into two: Low Lymphocyte–Albumin(LA) score (Group 1) and High Lymphocyte-Albumin score (Group 2). Demographics, clinical data, operative outcomes, and survival rates were compared. The LA score's predictive ability for lymph node positivity was assessed. Results Using a cut-off value of 6069.7, Group 1 had 59 patients (low value) and Group 2 had 45 (high value). Hospital readmissions due to wound infections were higher in Group 1 (16.9% vs. 2.2%, p=0.041). Both groups had similar tumor localization and total lymph nodes removed, but Group 1 had more positive lymph nodes (4 vs. 2, p=0.026). Survival rates were comparable (32.59 vs. 31.32 months, p=0.390). Conclusion Low LA scores correlate with a higher number of positive lymph nodes, serving as a postoperative quality assessment indicator.

A pathway for detection of gastric cancer biomarkers via using a layer-by-layer coated D-shaped grinding long-period fiber grating sensor

Gastric cancer significantly contributes to global cancer mortality, often leading to inoperable stages and high recurrence rates post-surgery. Elevated levels of G-17 and G-gly have been identified as potential risk factors, particularly in patients with duodenal ulcers. This study introduces an innovative D-shaped grinding long-period fiber grating sensor (D-LLPFGs) designed for non-invasive detection of the gastrin G-17 antigen, employing a layer-by-layer chemical self-assembly to bond G-17 antibodies onto the fiber surface through hydrogen bonding. The D-LLPFGs sensor demonstrated significant spectral shifts within 1 min of antigen-antibody interaction, highlighting its rapid detection capability. At an optimized antibody concentration of 4 μg/ml, antigen testing across different concentrations (10, 12.5, 20, 50 μg/ml) showed peak changes at 12.5 μg/ml antigen, with a 1.186 nm shift and 0.503 dB loss. The sensor exhibited a wavelength sensitivity of 0.095 nm/μg/ml, indicating its high sensitivity and potential in gastric cancer classification, diagnosis, and treatment. This research concludes that the D-shaped fiber sensor is an effective and sensitive tool for detecting G-17 antigen levels, presenting a significant advancement in non-invasive gastric cancer diagnosis. Its quick response time and high sensitivity highlight its potential for broad biomedical applications, offering a new avenue for early cancer detection and improving patient prognosis. The success of this study opens the door to further exploration and implementation of fiber optic sensors in clinical settings, marking a significant step forward in the fight against gastric cancer.

Investigating the Association between LncRNA NR2F2-AS1, miR-320b, and BMI1 in Gastric Cancer: Insights into Expression Profiles as Potential Biomarkers for Disease Management.

This study aims to investigate the potential role of lncRNA NR2F2-AS1 in the development of gastric cancer by affecting the levels of miR-320b and BMI1. Gastric cancer is a high-mortality malignancy, and understanding the underlying molecular mechanisms is crucial. Non-coding RNAs play an important role in gene expression, and their dysregulation can lead to tumor initiation and progression. This study aims to determine the pathological role of LncRNA NR2F2-AS1 in gastric cancer progression and its association with the clinicopathological characteristics of patients. Bioinformatics databases were used to predict the expression levels and interactions between the studied factors to achieve this objective. The expression pattern of NR2F2-AS1/miR- 320b/BMI1 in 40 pairs of tumor and adjacent normal tissues was examined using RT-PCR, IHC, and western blot. The correlation, ROC curve, and survival analyses were also conducted for the aforementioned factors. The results showed an increase of more than 2-fold for BMI-1 and lncRNA NR2F2-AS1 in lower stages, and the elevation continued with the increasing stage of the disease. This correlated with significant downregulation of miR-320b and PTEN, indicating their association with gastric cancer progression and decreased patient survival. LncRNA NR2F2-AS1 acts as an oncogene by influencing the level of miR-320b, altering the amount of BMI1. A reduction in the amount of miR-320b against lncRNA NR2F2-AS1 and BMI1 directly correlates with a reduced overall survival rate of patients, especially if this disproportion is more than 3.0. ROC curve analysis indicated that alteration in the lncRNA NR2F2-AS1 level showed more than 98.0% sensitivity and specificity to differentiate the lower from higher stages of GC and predict the early onset of metastasis. In conclusion, these results suggest that NR2F2-AS1/miR-320b/BMI1 has the potential to be a prognostic as well as diagnostic biomarker for gastric cancer.

KIAA1429 promotes gastric cancer progression by destabilizing RASD1 mRNA in an m6A-YTHDF2-dependent manner

BackgroundKIAA1429, a regulatory subunit of the N6-methyladenosine (m6A) methyltransferase complex, has been implicated in the progression of various cancers. However, the role of KIAA1429 in gastric cancer (GC) and its underlying mechanisms remain elusive. This study aimed to investigate the role of KIAA1429 in GC and to elucidate the underlying mechanisms.MethodsThe expression patterns and clinical relevance of KIAA1429 in GC were assessed using quantitative real-time PCR (qRT-PCR), Western blotting, immunohistochemistry (IHC), and bioinformatic analysis. In vitro and in vivo loss- and gain-of-function assays, m6A dot blot assays, methylated RNA immunoprecipitation sequencing (MeRIP-seq), RNA-seq, MeRIP-qPCR, dual luciferase reporter assays, RNA stability assays, RNA immunoprecipitation (RIP) assays, and RNA pull-down assays were performed to investigate the biological functions and underlying molecular mechanisms of KIAA1429 in GC.ResultsBoth the mRNA and protein expression of KIAA1429 were greater in GC tissues than in normal gastric tissues. High KIAA1429 expression correlated positively with poor prognosis in GC patients. KIAA1429 not only promoted GC cell proliferation, colony formation, G2/M cell cycle transition, migration, and invasion in vitro but also enhanced GC tumor growth and metastasis in vivo. Mechanistically, KIAA1429 increased the m6A level of RASD1 mRNA and enhanced its stability in an m6A-YTHDF2-dependent manner, thereby upregulating its expression. RASD1 knockdown partially rescued the KIAA1429 knockdown-induced impairment of pro‑oncogenic ability in GC cells. The expression levels of KIAA1429 and RASD1 were negatively correlated in GC tissues.ConclusionsKIAA1429 plays a pro‑oncogenic role in GC by downregulating RASD1 expression through destabilizing RASD1 mRNA in an m6A-YTHDF2-dependent manner. KIAA1429 may serve as a prognostic biomarker and therapeutic target for GC.

Circ_0004592: An auxiliary diagnostic biomarker for gastric cancer.

Gastric cancer (GC) has a high mortality rate, and robust diagnostic biomarkers are currently lacking. However, the clinical relevance of circular RNAs (circRNAs) as GC biomarkers remains largely unexplored. To evaluate the potential of novel circRNA circ_0004592 in the early screening and prognosis of GC. High-throughput sequencing of circRNAs was performed to screen for potential target molecules. Circ_0004592 expression was examined in GC tissues, cells, and plasma. Plasma samples were collected from healthy subjects' patients, as well as from patients with benign lesions, precancerous lesions, and GC, whereafter the diagnostic accuracy of circ_0004592 was evaluated. The correlation between circ_0004592 levels in plasma and clinicopathological data of patients with GC was further analyzed. Circ_0004592 was upregulated in both the tissue and plasma of patients with GC. Further, circ_0004592 expression was higher in patients with precancerous lesions than in healthy controls while being highest in patients with GC. In the same patient, the postoperative plasma level of circ_0004592 was lower than that in the preoperative period. Moreover, circ_0004592 level was significantly correlated with tumor differentiation, tumor depth, and lymph node metastasis. The area under the curve (AUC) of plasma circ_0004592 exhibited high sensitivity and specificity for differentiating patients with GC from healthy donors. Diagnosis based on circ_0004592, carcinoembryonic antigen, and cancer antigen 199 achieved a superior AUC and was highly sensitive. Plasma circ_0004592 may represent a potential non-invasive auxiliary diagnostic biomarker for patients with GC.

Terpene extract from the stem of Celastrus orbiculatus inhibits actin cytoskeleton remodelling in gastric cancer cells by regulating the protein interaction between PTBP1 and ACTN4

Adjuvant chemoradiotherapy, molecular targeted therapy, and immunotherapy are frequently employed to extend the survival of patients with advanced gastric cancer (GC). However, most of these treatments have toxic side effects, drug resistance, and limited improvements in survival and quality of life. Therefore, it is crucial to discover and develop new medications targeting GC that are highly effective and have minimal toxicity. In previous studies, the total terpene extract from the stem of Celastrus orbiculatus demonstrated anti-GC activity; however, the specific mechanism was unclear. Our research utilising co-immunoprecipitation-mass spectrometry (Co-IP-MS), polypyrimidine tract binding protein 1 (ptbp1) clustered regularly interspaced short palindromic repeat-associated protein 9 (Cas9)-knockout (KO) mouse model, tissue microarray, and functional experiments suggests that alpha actinin-4 (ACTN4) could be a significant biomarker of GC. PTBP1 influences actin cytoskeleton restructuring in GC cells by interacting with ACTN4. Celastrus orbiculatus stem extract (COE) may directly target ACTN4 and affect the interaction between PTBP1 and ACTN4, thereby exerting anti-GC effects.