Prognosis Of Gastric Cancer Patients Research Articles

The association and clinicopathological significance of Integrin alphavbeta6 and Rac1 expression in gastric carcinoma.

The present study investigate the expression and correlation of ITGB6 and Rac1 proteins in gastric cancer tissues. By exploring the clinical significance and functions of these proteins, we aimed to gain further insights into the mechanisms underlying gastric cancer development. In this study, a total of 198 patients diagnosed with gastric cancer and who underwent gastrectomy between July 2010 to October 2012 were included. The median follow-up time was 52.00 months. To evaluate the factors influencing overall survival, Kaplan-Meier survival curve analysis and Cox regression analysis were conducted. Furthermore, an independent prognostic factor-based nomogram was constructed and validated to predict survival outcomes in gastric cancer patients. In addition, in vitro experiments including CCK8 and Transwell assays were conducted to explore the roles of ITGB6 and Rac1 in gastric cancer. The expression levels of ITGB6 and Rac1 in gastric cancerous and paraneoplastic tissues were detected by immunohistochemistry. The correlation and clinical significance of the two proteins were also investigated. ITGB6 expression showed significant associations with tumor size (P=0.030), pathological grading (P=0.013), location (P=0.031), N stage (P=0.002), and clinical stage (P=0.002). Additionally, we found that tumor size (P=0.013), tumor's anatomical location (P=0.031), N stage (P=0.002), clinical stage (P=0.035), and survival status (P<0.001) were significantly associated with the expression of Rac1. ITGB6 was moderately correlated with Rac1 (r=0.285, P<0.001). Both the Kaplan-Meier survival analysis and Cox regression model analysis demonstrated that the presence of positive expression of ITGB6 and Rac1 proteins served as independent prognostic factors for gastric cancer. These findings highlight the potential of ITGB6 and Rac1 as valuable markers for predicting the prognosis of gastric cancer patients (HR=2.212 P<0.001 and HR=2.073 P=0.001), with a significant poorer trend for 5-year survival (P<0.0001, respectively, the log-rank test). Additionally, subsequent in vitro experiments preliminarily demonstrated that ITGB6 and Rac1 promoted the proliferation, migration and invasion of gastric cancer cells, and ITGB6 may functions via targeting Rac1. ITGB6 and Rac1 are indicators of poor prognosis and tumor progression in gastric cancer patients. The potential signaling pathways associated with both may provide useful targets for the prevention and treatment of gastric cancer.

Clinical presentation and delay to diagnosis and treatment in Mexican patients with gastric cancer.

291 Background: Gastric cancer is the fifth leading cause of cancer-related deaths in Mexico. Diagnosis is often made at advanced stages, resulting in a poor prognosis. The delay from the onset of the first symptom to diagnosis and treatment could influence the poor prognosis of gastric cancer patients (pts) in our country. In Mexico, information on this topic is limited. We aim to investigate the time delay between the onset of symptoms, histological diagnosis, and initiation of oncological treatment in pts with gastric adenocarcinoma. Methods: We conducted a retrospective review of the clinical records at our institution of all pts with confirmed histological diagnosis of gastric adenocarcinoma (GC) treated between Jan 2005 and Dec 2017. Overall Survival (OS) was estimated using the Kaplan-Meier method. Groups were compared using Log-Rank test. Results: We included 270 pts with confirmed histopathological diagnosis of GC, 53.3% (n=144) women, median age 58 years (IQR 25-75); 44% (n=121) reported family history of cancer, 39.6% (n=107) smoking, H. pylori infection was documented in 22% (n=61). Symptoms before diagnosis were present in 98.5% (n=266) of pts, most common were: weight loss 77.4% (n=209), fatigue 51.9% (n=140), early satiety 51.1% (n=138), nausea 48.9% (n=132), vomiting 48.1% (n=130), dysphagia 21.5% (n=58), and gastrointestinal bleeding 37.8% (n=102). The most common method for histological diagnosis was endoscopy with biopsy in 86.7% (n=234). The median time between the onset of symptoms and histopathological diagnosis was 4.21 (IQR 2.25–8.48) months (m), between the onset of symptoms and the initiation of oncological treatment 5.28 (IQR 2.86–9.52) m, and between histopathological diagnosis and oncological treatment 0.60 (IQR 0.13–1.21) m. 72.6% (n=196) of cases were stage IV, 14.1% (n=38) stage III, 8.1% (n=22) stage II, 4.8% (n=13) and stage 0 or I. The median OS for the entire cohort was 7.2 m, 3.7 m for stage IV, 17.3 m for stage III, and 84 m for stage I. Median OS for stage II was not reached, and it was 58% at 5 years. Symptoms associated with worse or better survival are shown in table. Conclusions: Reducing delays in histopathological diagnosis from symptom onset could lead to earlier detection and curative treatments. Identifying alarm signs and appropriate patient navigation would enable earlier diagnosis and early treatment. [Table: see text]

Study of miRNA and lymphocyte subsets as potential biomarkers for the diagnosis and prognosis of gastric cancer.

The aim of this study was to identify the expression of miRNA and lymphocyte subsets in the blood of gastric cancer (GC) patients, elucidate their clinical significance in GC, and establish novel biomarkers for the early diagnosis and prognosis of GC. The expression of miRNAs in the serum of GC patients was screened using second-generation sequencing and detected using qRT-PCR. The correlation between miRNA expression and clinicopathological characteristics of GC patients was analyzed, and molecular markers for predicting cancer were identified. Additionally, flow cytometry was used to detect the proportion of lymphocyte subsets in GC patients compared to healthy individuals. The correlations between differential lymphocyte subsets, clinicopathological features of GC patients, and their prognosis were analyzed statistically. The study revealed that hsa-miR-1306-5p, hsa-miR-3173-5p, and hsa-miR-296-5p were expressed at lower levels in the blood of GC patients, which is consistent with miRNA-seq findings. The AUC values of hsa-miR-1306-5p, hsa-miR-3173-5p, and hsa-miR-296-5p were found to be effective predictors of GC occurrence. Additionally, hsa-miR-296-5p was found to be negatively correlated with CA724. Furthermore, hsa-miR-1306-5p, hsa-miR-3173-5p, and hsa-miR-296-5p were found to be associated with the stage of the disease and were closely linked to the clinical pathology of GC. The lower the levels of these miRNAs, the greater the clinical stage of the tumor and the worse the prognosis of gastric cancer patients. Finally, the study found that patients with GC had lower absolute numbers of CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, and lymphocytes compared to healthy individuals. The quantity of CD4+ T lymphocytes and the level of the tumor marker CEA were shown to be negatively correlated. The ROC curve and multivariate logistic regression analysis demonstrated that lymphocyte subsets can effectively predict gastric carcinogenesis and prognosis. These miRNAs such as hsa-miR-1306-5p, hsa-miR-3173-5p, hsa-miR-296-5p and lymphocyte subsets such as the absolute numbers of CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, lymphocytes are down-regulated in GC and are closely related to the clinicopathological characteristics and prognosis of GC patients. They may serve as new molecular markers for predicting the early diagnosis and prognosis of GC patients.

Construction of an immune-related risk score signature for gastric cancer based on multi-omics data

Early identification of gastric cancer (GC) is associated with a superior survival rate compared to advanced GC. However, the poor specificity and sensitivity of traditional biomarkers suggest the importance of identifying more effective biomarkers. This study aimed to identify novel biomarkers for the prognosis of GC and construct a risk score (RS) signature based on these biomarkers, with to validation of its predictive performance. We used multi-omics data from The Cancer Genome Atlas to analyze the significance of differences in each omics data and combined the data using Fisher's method. Hub genes were subsequently subjected to univariate Cox and LASSO regression analyses and used to construct the RS signature. The RS of each patient was calculated, and the patients were divided into two subgroups according to the RS. The RS signature was validated in two independent datasets from the Gene Expression Omnibus and subsequent analyses were subsequently conducted. Five immune-related genes strongly linked to the prognosis of GC patients were obtained, namely CGB5, SLC10A2, THPO, PDGFRB, and APOD. The results revealed significant differences in overall survival between the two subgroups (p < 0.001) and indicated the high accuracy of the RS signature. When validated in two independent datasets, the results were consistent with those in the training dataset (p = 0.003 and p = 0.001). Subsequent analyses revealed that the RS signature is independent and has broad applicability among various GC subtypes. In conclusion, we used multi-omics data to obtain five immune-related genes comprising the RS signature, which can independently and effectively predict the prognosis of GC patients with high accuracy.

Prognostic significance and relationship of SMAD3 phospho-isoforms and VEGFR-1 in gastric cancer: A clinicopathological study.

The TGF-β/SMAD3 and VEGFR-1 signaling pathways play important roles in gastric cancer metastasis. SMAD3 phosphorylation is a crucial prognostic marker in gastric cancer. To determine the prognostic value and relationship of SMAD3 phospho-isoforms and VEGFR-1 in gastric cancer. This was a single-center observational study which enrolled 98 gastric cancer patients and 82 adjacent normal gastric tissues from patients aged 32-84 years (median age 65) between July 2006 and April 2007. Patients were followed up until death or the study ended (median follow-up duration of 28.5 mo). The samples were used to generate tissue microarrays (TMAs) for immunohistochemical (IHC) staining. The expressions of TGF-β1, pSMAD3C(S423/425), pSMAD3L(S204), and VEGFR-1 in gastric cancer (GC) tumor tissue and normal tissue were measured by IHC staining using TMAs obtained from 98 GC patients. Prognosis and survival information of the patients was recorded by Outdo Biotech from May 2007 to July 2015. The relationship between TGF-β1, pSMAD3C(S423/425), pSMAD3L(S204), and VEGFR-1 protein expression levels was analyzed using Pearson's correlation coefficient. The relationship between protein expression levels and clinicopathological parameters was analyzed using the Chi-squared test. A survival curve was generated using the Kaplan-Meier survival analysis. TGFβ-1 and VEGFR-1 expression was significantly upregulated in gastric cancer tissue compared to adjacent non-cancerous tissue. The positive expression of phosphorylated isoforms of Smad3 varied depending on the phosphorylation site [pSMAD3C(S423/425): 51.0% and pSMAD3L(S204): 31.6%]. High expression of pSMAD3L(S204) was significantly correlated with larger tumors (P = 0.038) and later N stages (P = 0.035). Additionally, high expression of VEGFR-1 was closely correlated with tumor size (P = 0.015) and pathological grading (P = 0.013). High expression of both pSMAD3L(S204) and VEGFR-1 was associated with unfavorable outcomes in terms of overall survival (OS). Multivariate analysis indicated that high expression of pSMAD3L(S204) and VEGFR-1 were independent risk factors for prognosis in GC patients. VEGFR-1 protein expression was correlated with TGF-β1 (r = 0.220, P = 0.029), pSMAD3C(S423/425) (r = 0.302, P = 0.002), and pSMAD3L(S204) (r = 0.201, P = 0.047), respectively. Simultaneous overexpression of pSMAD3L(S204) and VEGFR-1 was associated with poor OS in gastric cancer patients. Co-upregulation of pSMAD3L(S204) and VEGFR-1 can serve as a predictive marker for poor gastric cancer prognosis, and pSMAD3L(204) may be involved in enhanced gastric cancer metastasis in a VEGFR-1-dependent manner.

Tumor-infiltrating monocytic myeloid-derived suppressor cells contribute to the development of an immunosuppressive tumor microenvironment in gastric cancer.

Gastric cancer (GC) is characterized by an immunosuppressive and treatment-resistant tumor immune microenvironment (TIME). Here, we investigated the roles of different immunosuppressive cell types in the development of the GC TIME. Single-cell RNA sequencing (scRNA-seq) and multiplex immunostaining of samples from untreated or immune checkpoint inhibitor (ICI)-resistant GC patients were used to examine the correlation between certain immunosuppressive cells and the prognosis of GC patients. The results of the scRNA-seq analysis revealed that tumor-infiltrating monocytic myeloid-derived suppressor cells (TI-M-MDSCs) expressed higher levels of genes with immunosuppressive functions than other immunosuppressive cell types. Additionally, M-MDSCs in GC tissues expressed significantly higher levels of these markers than adjacent normal tissues. The M-MDSCs were most enriched in GC tissues relative to adjacent normal tissues. Among the immunosuppressive cell types assessed, the M-MDSCs were most enriched in GC tissues relative to adjacent normal tissues; moreover, their presence was most strongly associated with a poor prognosis. Immediate early response 3 (IER3), which we identified as a differentially expressed gene between M-MDSCs of GC and adjacent normal tissues, was an independent poor prognostic factor in GC patients (P = 0.0003). IER3+ M-MDSCs expressed higher levels of genes with immunosuppressive functions than IER3- M-MDSCs and were abundant in treatment-resistant GC patients. The present study suggests that TI-M-MDSCs, especially IER3+ ones, may play a predominant role in the development of the immunosuppressive and ICI-resistant GC TIME.

The phase separation of extracellular matrix protein matrilin-3 from cancer-associated fibroblasts contributes togastric cancer invasion.

Cancer-associated fibroblast (CAF) has emerged as a key contributor to the remodeling of tumor microenvironment through the expression and secretion of extracellular matrix (ECM) proteins, thereby promoting carcinogenesis. However, the precise contribution of ECM proteins from CAFs to gastric carcinogenesis remains poorly understood. In this study, we find that matrilin-3 (MATN3), an upregulated ECM protein associated with poorer prognosis in gastric cancer patients, originates from CAFs in gastric cancer tissues. Ectopic expression of MATN3 in CAFs significantly promotes the invasion of gastric cancer cells, which can be attenuated by neutralizing MATN3 with its antibody. Notably, a portion of MATN3 protein is found to form puncta in gastric cancer tissues ECM. MATN3 undergoes phase separation, which is mediated by its low complexity (LC) and coiled-coil (CC) domains. Moreover, overexpression of MATN3 deleted with either LC or CC in CAFs is unable to promote the invasion of gastric cancer cells, suggesting that LC or CC domain is required for the effect of CAF-secreted MATN3 in gastric cancer cell invasion. Additionally, orthotopic co-injection of gastric cancer cells and CAFs expressing MATN3, but not its ΔLC and ΔCC mutants, leads to enhanced gastric cancer cell invasion in mouse models. Collectively, our works suggest that MATN3 is secreted by CAFs and undergoes phase separation, which promotes gastric cancer invasion.

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

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

High expression of TRIP13 is associated with tumor progression in H. pylori infection induced gastric cancer

Background/objectiveH. pylori is a recognized bacterial carcinogen in the world to cause gastric cancer (GC). However, the molecular mechanism of H. pylori infection-induced GC is not completely clear. Thus, there is an urgent need to reveal the precise mechanisms regulating cancer development due to H. pylori infection. MethodsGEO microarray databases and TCGA databases were extracted for the analysis of different expression genes (DEGs). Then, Kaplan-Meier Plotter was used for prognostic analysis. Functional enrichment analysis of TRIP13 was performed by metascape database and TIMER database. Specific role of TRIP13 in GC with H. pylori infection was confirmed by CCK8, cell cycle analysis and WB. ResultsA total 10 DEGs were substantially elevated in GC and H. pylori+ tissues and might be associated with H. pylori infection in GC and only the highly expressed TRIP13 was statistically associated with poor prognosis in GC patients. Meanwhile, TRIP13 were upregulated in both CagA-transfected epithelial cells and GC cells. And TRIP13 deficiency inhibited cell proliferation and arrested the cell cycle at the G1 phase. ConclusionOur study suggested that high expression of TRIP13 can promote the proliferation, cell cycle in GC cells, which could be used as a biomarker for H. pylori infection GC.

ATP11A Promotes Epithelial-mesenchymal Transition in Gastric Cancer Cells via the Hippo Pathway.

Background: ATP11A, a P-type ATPase, functions as flippases at the plasma membrane to maintain cellular function and vitality in several cancers. However, the role of ATP11A in gastric cancer remains unknown. This study aimed to identify ATP11A related to the biological behavior of gastric cancer, and elucidate the underlying mechanism. Methods: The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases were used to analyze the expression and prognosis of ATP11A. The biofunctions of ATP11A were explored through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA). The expression of ATP11A were validated by immunohistochemistry (IHC), qRT-PCR and Western blotting. Transwell, wound healing, CCK8 and colony-formation were to detected the migration, invasion and proliferation of gastric cancer cells. The epithelial-mesenchymal transition (EMT) and Hippo pathway markers were examined by Western blotting. Results: The expression of ATP11A was higher in gastric cancer tissues than in normal tissues, and high ATP11A levels were related to worse prognosis of gastric cancer patients. Additionally, we proved that ATP11A promoted the migration, invasion and proliferation in gastric cancer cells. Furthermore, ATP11A was found to promote EMT by devitalizing the Hippo pathway. Conclusion: ATP11A promoted migration, invasion, proliferation and EMT via Hippo signaling devitalization in gastric cancer cells.

HNF4A-Bridging the Gap Between Intestinal Metaplasia and Gastric Cancer.

Intestinal metaplasia (IM) of gastric epithelium has traditionally been regarded as an irreversible stage in the process of the Correa cascade. Exploring the potential molecular mechanism of IM is significant for effective gastric cancer prevention. The GSE78523 dataset, obtained from the Gene Expression Omnibus (GEO) database, was analyzed using RStudio software to identify the differently expressed genes (DEGs) between IM tissues and normal gastric epithelial tissues. Subsequently, gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, Gene Set Enrichment Analysis (GESA), and protein-protein interaction (PPI) analysis were used to find potential genes. Additionally, the screened genes were analyzed for clinical, immunological, and genetic correlation aspects using single gene clinical correlation analysis (UALCAN), Tumor-Immune System Interactions Database (TISIDB), and validated through western blot experiments. Enrichment analysis showed that the lipid metabolic pathway was significantly associated with IM tissues and the apolipoprotein B (APOB) gene was identified in the subsequent analysis. Experiment results and correlation analysis showed that the expression of APOB was higher in IM tissues than in normal tissues. This elevated expression of APOB was also found to be associated with the expression levels of hepatocyte nuclear factor 4A (HNF4A) gene. HNF4A was also found to be associated with immune cell infiltration to gastric cancer and was linked to the prognosis of gastric cancer patients. Moreover, HNF4A was also highly expressed in both IM tissues and gastric cancer cells. Our findings indicate that HNF4A regulates the microenvironment of lipid metabolism in IM tissues by targeting APOB. Higher expression of HNF4A tends to lead to a worse prognosis in gastric cancer patients implying it may serve as a predictive indicator for the progression from IM to gastric cancer.

LncRNA LINC01278 Regulates the Prognosis and Related Mechanisms of Gastric Cancer by Targeting miR-129-5p.

Gastric cancer, a prevalent malady within the digestive tract, has a complex pathological mechanism and numerous patients. The regulation of gastric cancer process by long non-coding RNA (lncRNA) presented new prospects for the study of its molecular mechanism and the treatment of patients. The abnormal expressed genes in gastric cancer were screened by GSE193109 dataset. The correlation between LINC01278 and the likelihood of survival in patients suffering from gastric cancer was investigated by Kaplan-Meier survival curve and multivariate Cox analysis. LINC01278 in gastric cancer tissue samples and cells was verified via RT-qPCR. The cell counting kit-8 (CCK-8) and transwell assay were selected to detect the growth activity of gastric cancer cells. The association between LINC01278 and miR-129-5p was validated through luciferase reporter assay and RNA-binding protein immunoprecipitation (RIP) assay. Correlation analysis of clinical features revealed an association between LINC01278 and the prognosis in gastric cancer patients. LINC01278 was actively expressed in gastric cancer, which exerts a tumor-promoting effect. Silencing LINC01278 suppressed the biological function of tumor cells through spongiform miR-129-5p. LINC01278 has the potential to serve as a novel biomarker, offering new avenues of research for the prognosis and treatment of gastric cancer.

The Relationship between Inflammation Level Related Indicators and Prognosis of Gastric Cancer Patients

The Relationship between Inflammation Level Related Indicators and Prognosis of Gastric Cancer Patients

Prognostic value and immunomodulatory role of DNM1L in gastric adenocarcinoma.

Mitochondrial fusion and fission are critical for the morphology and function of cells. DNM1L encodes dynamin-related protein 1 (DRP1), a key protein mediating mitochondrial fission, which is upregulated in a variety of cancers and is strongly associated with tumorigenesis. We aim to investigate the relationship between DNM1L and the prognosis of gastric cancer, as well as to explore the function and mechanism of DNM1L in gastric cancer (GC). In this study, we analyzed the expression differences of DNM1L in gastric cancer tissues and paracancerous tissues using The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database. This was followed by validation through tissue microarrays. We then utilized the cohort information from these microarrays to explore the relationship between DNM1L expression and gastric cancer prognosis. Furthermore, we conducted enrichment analysis to investigate the function and mechanisms of DNM1L in gastric cancer, and lastly, we performed immune cell infiltration analysis using the CIBERSORT algorithm. We discovered that the expression of DNM1L is elevated in GC tissues. TCGA data showed that the overexpression of DNM1L was positively correlated with the T-stage of GC but not with lymph node metastasis, which was also corroborated by our immunohistochemistry experiments. Based on the Kaplan-Meier curves, the high DNM1L expression was remarkably correlated with poor overall survival in patients with GC. In addition, results of COX regression analysis indicated that high DNM1L expression was an independent prognostic factor in patients with GC. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene set enrichment analysis (GSEA) showed that DNM1L was closely associated with multiple signaling pathways and immune responses. CIBERSORT analysis indicated that increased DNM1L expression may affect the infiltration of immune cells in the tumor microenvironment. The results of this study indicate that DNM1L is upregulated in gastric cancer (GC) and positively correlates with the T-stage and poor prognosis of GC patients, and it plays an important role in tumor immune infiltration.

Evaluation of Quality of Life and Prognosis of Gastric Cancer Patients After Laparoscopic Subtotal Gastrectomy.

The clinical significance of laparoscopic subtotal gastrectomy (LsTG) with a small remnant stomach remains unclear in patients with gastric cancer, including at an advanced stage. The present study assessed postoperative quality of life (QOL) and survival after LsTG compared with laparoscopic total gastrectomy (LTG). We retrospectively analyzed consecutive patients with gastric cancer who underwent LsTG (n=26) or LTG (n=26). Surgical outcome, postoperative nutritional status, QOL, and prognosis were compared between the LsTG and LTG groups. The Postgastrectomy Syndrome Assessment Scale was used to evaluate postoperative QOL. Operating time was significantly shorter (p<0.01) and postoperative morbidity was significantly lower (p=0.04) in the LsTG than in the LTG group. The reduction in body weight after surgery was significantly greater in the LTG than in the LsTG group (p<0.01). The Postgastrectomy Syndrome Assessment Scale revealed that, compared with LTG, LsTG significantly improved postoperative QOL (p<0.05). There was no significant difference in relapse-free survival and cancer-specific survival between the two groups. Three patients in the LTG group died of pneumonia and overall survival was significantly longer in the LsTG group (p=0.01). This study demonstrated the efficacy of LsTG with a small remnant stomach to prevent a decline in postoperative QOL and non-cancer-related death.

Application of pyroptosis score in the treatment and prognosis evaluation of gastric cancer.

Pyroptosis is a kind of proinflammatory programmed cell death mediated by inflammasome. It affects the occurrence and development of gastric cancer through different ways, showing dual effects. On the one hand, inflammasome-mediated inflammatory response is highly likely to participate in the formation and development of early tumors; on the other hand, drugs can inhibit the deterioration process of tumor proliferation, invasion and metastasis through activating the pathways of inflammasome and pyroptosis. Recently, many agents based on pyroptosis have been found to inhibit gastric cancer by promoting the secondary pyroptosis pathway, regulating NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and inhibiting caspase-1. The establishment of cell pyrodeath models can predict the prognosis of gastric cancer patients. Most of the models show that gastric cancer patients with high pyroptosis level have better prognosis and longer overall survival. Pyroptosis scores can also be used to predict the response of gastric cancer patients to immunotherapy and to screen potential anti-gastric cancer drugs. Therefore, in-depth understanding of the potential mechanism of pyroptosis affecting the progression of gastric cancer and the role of pyroptosis score in the treatment and prognosis assessment of gastric cancer will be helpful to find a new and effective method for the treatment of gastric cancer.

A predictive model and rapid multi-dynamic algorithm developed based on tumor-stroma percentage in gastric cancer: a retrospective, observational study.

Tumor-stroma percentage (TSP) is a prognostic risk factor in numerous solid tumors. Despite this, the prognostic significance of TSP in gastric cancer (GC) remains underexplored. Through the development of a personalized predictive model and a semi-automatic identification system, our study aimed to fully unlock the predictive potential of TSP in GC. We screened GC patients from Shanghai General Hospital (SGH) between 2012 and 2019 to develop and validate a nomogram. Univariate and multivariate Cox proportional hazards regression analyses were employed to identify independent prognostic factors influencing the prognosis for GC patients. The nomogram was further validated externally by using a cohort from Bengbu Medical College (BMC). All patients underwent radical gastrectomy, with those diagnosed with locally advanced GC receiving adjuvant chemotherapy. The primary outcome measured was overall survival (OS). The semi-automatic identification of the TSP was achieved through a computer-aided detection (CAD) system, denoted as TSP-cad, while TSP identified by pathologists was labeled as TSP-visual. A total of 813 GC patients from SGH and 59 from BMC were enrolled in our study. TSP-visual was identified as an adverse prognostic factor for OS in GC and was found to be associated with pathological Tumor Node Metastasis staging system (pTNM) stage, T stage, N stage, perineural invasion (PNI), lymphovascular invasion (LVI), TSP-visual, tumor size, and other factors. Multivariate Cox regression using the training cohort revealed that TSP-visual (hazard ratio [HR], 2.042; 95% confidential interval [CI], 1.485-2.806; P < 0.001), N stage (HR, 2.136; 95% CI, 1.343-3.397; P = 0.010), PNI (HR , 1.791; 95% CI, 1.270-2.526; P = 0.001), and LVI (HR, 1.482; 95% CI, 1.021-2.152; P = 0.039) were independent predictors. These factors were incorporated into a novel nomogram, which exhibited strong predictive accuracy for 5-year OS in the training, internal validation, and external validation cohorts (area under the curve = 0.744, 0.759, and 0.854, respectively). The decision curve analysis of the nomogram and concordance indexes across the three cohorts outperformed the traditional pTNM (P < 0.05). Additionally, TSP-cad assessment using a rapid multi-dynamic algorithm demonstrated good agreement with TSP-visual. The novel nomogram based on TSP could effectively identify individuals at risk of a poor prognosis among patients with GC. TSP-cad is anticipated to enhance the evaluation process of TSP.

ESRP1-driven alternative splicing of CLSTN1 inhibits the metastasis of gastric cancer

Tumor metastasis severely limits the prognosis of gastric cancer patients. RNA-binding proteins (RBPs) are crucial in tumor metastasis, yet there is limited research into their involvement in gastric cancer. Here, we found that ESRP1, a RBP specific in epithelial cells, is important in regulating the metastasis of gastric cancer cells. ESRP1 is negatively correlated with distant metastasis and lymph node metastasis in gastric cancer patients. And we demonstrated that ESRP1 inhibit migration and invasion of gastric cancer in vitro and in vivo. Mechanistically, ESRP1 promotes exon 11 alternative splicing of CLSTN1 pre-mRNA. The post-splicing short CLSTN1 stabilizes the Ecadherin/β-catenin binding structure, and promotes β-catenin protein ubiquitination and degradation, thereby inhibiting the migration and invasion of gastric cancer cells. Our study highlights the role of ESRP1 in regulating metastasis of gastric cancer and extends its mechanism. These results provide a possibility for ESRP1 and CLSTN1 to become therapeutic targets for metastasis of gastric cancer.

Hypoxia-based critical gene biomarkers as prognostic reporters for gastric adenocarcinoma.

Gastric cancer is the most common malignant tumour of the digestive system, yet there is a lack of reported prognostic biomarkers for STAD patients. Transcriptomic expression data of STAD from GEO database, single cell sequencing data from OMIX gastric cancer database. Conservative molecular typing of gastric cancer was constructed using non-negative matrix factorization (NMF). The abundance of 28 immune cells in the tumour samples was assessed using ssGSEA. The R package "oncoPredict" was used to predict chemotherapy response. TIDE website for immunotherapy response prediction. Finally, single cell analysis was performed to clarify the specific type annotation of STAD cells and to analysis their spatial expression. Hypoxia-score demonstrated excellent prognostic discrimination in TCGA gastric cancer samples. Among multiple deconvolution-based algorithms for immune infiltration, Hypoxia-score presented a general immunosuppressive efficacy across multiple datasets, as evidenced by a broad negative correlation with immune cell infiltration. By the likelihood that each group may have specific drug sensitivity to multiple chemotherapeutic and targeted agents. Results showed that high-risk scoring patients were more sensitive to Staurosporine, Sabutoclax, and AZD8055, while low-risk patients were more sensitive to Bortezomib, Dactinomycin, Docetaxel, Daporinad, Sepantronium, and bromide. In the immunotherapy cohort, the Hypoxia-score presented the ability to discriminate for immunotherapy efficacy. The distribution of Hypoxia-score in single-cell descending space was calculated using AddModuleScore and was found to be distributed across the various cell types annotated in the single-cell analysis. It is suggested that various cells in the tumour microenvironment are involved in hypoxia gene set processes to varying degrees. The Hypoxia-score proves to be a valuable tool for assessing the prognosis of gastric cancer patients and guiding drug treatments, providing significant guidance for clinical diagnosis and treatment in the context of gastric cancer.

Pretreatment controlling nutritional status (CONUT) score and carcinoembryonic antigen level provide tumor progression and prognostic information in gastric cancer: A retrospective study.

This study explores the role of combining the controlling nutritional status (CONUT) score and the carcinoembryonic antigen (CEA) level on predicting tumor stage and prognosis in gastric cancer (GC) patients. A total of 682 GC patients were included in this retrospective study. CONUT scores and CEA levels were combined to establish a new scoring system: CONUT-CEA score. cutoff values for distinguishing patients between stage IV and non-stage IV were established by receiver operating characteristic curves. cutoff values for predicting prognosis were determined by maximum χ2 method. The CONUT and CEA cutoff values for discriminating stage IV patients from non-stage IV patients were 2.0 and 5.58 ng/mL, respectively. Logistic regression model demonstrated that high CONUT-CEA score was related to advanced tumor stage. Among non-stage IV patients, CONUT and CEA cutoff values of 2.0 and 9.50 ng/mL predicted overall survival (OS), respectively. The Cox proportional risk model revealed that high CONUT-CEA score was notable related to decreased OS (2 vs 0: hazard ratios (HR) = 2.358, 95% confidence intervals (CI) = 1.412-3.940, P = .001) and decreased disease-free survival (2 vs 0: HR = 1.980, 95% CI = 1.072-3.656, P = .003). The CONUT-CEA score may be a good biomarker for predicting tumor stage and prognosis in GC patients.