Gastric Cancer Patients Research Articles

Pre-treatment of hyponatremia as a biomarker for poor immune prognosis in advanced or metastatic gastric cancer: A retrospective case analysis

ABSTRACT Hyponatremia, a prevalent electrolyte imbalance among tumor patients, has often been overlooked regarding its prognostic significance for immunotherapy. In this study, we delved into the prognostic ramifications of hyponatremia in advanced gastric cancer (AGC) patients undergoing immunotherapy. Enrolling AGC patients diagnosed between December 2014 and May 2021, we extracted pertinent data from electronic medical records, with a median follow-up of 35.8 months. Kaplan–Meier curves illuminated patients’ progression-free survival (PFS) and overall survival (OS), while survival disparities were tested using the Mantel–Haenszel log rank test. COX and logistic regressions were employed to scrutinize the correlation between serum sodium levels and prognosis in 268 AGC patients, both at baseline and during treatment. Notably, patients with hyponatremia exhibited shorter PFS (4.7 vs 2.1 months, p = .001*) and OS (12.5 vs 3.9 months, p < .001*). Serum sodium emerged as an independent prognostic factor for both PFS (HR = 1.773; 95% CI 1.067–2.945; p = .001*) and OS (HR = 1.773; 95% CI 1.067–2.945; p = .003*). Subgroup analysis revealed that AGC patients with hyponatremia derived no benefit from immunotherapy in terms of PFS and OS. Strikingly, a decrease in serum sodium during immunotherapy was associated with early relapse and mortality. Based on these findings, we hypothesize that hyponatremia portends poor prognostic outcomes in AGC patients treated with immunotherapy and may serve as a valuable prognostic biomarker. However, further large-scale prospective studies are warranted to validate these observations.

Body Composition Decrease and Impact on Clinical Outcome in Gastric Cancer Patients Undergoing Radical Gastrectomy After Neoadjuvant Treatment

This study investigates the impact of neoadjuvant therapy (NT) on body composition and its correlation with long-term survival and other clinical outcomes in patients with advanced gastric cancer. We utilized Computed Tomography (CT) scans to measure body composition before and after NT, including Subcutaneous Adipose Tissue Index (SATI), Visceral Adipose Tissue Index (VATI), Skeletal Muscle Index (SMI), and Muscle Density (MA). We then analyzed the decrease in body composition in relation to tumor regression, inflammatory markers, nutritional scores, and long-term survival. Our findings reveal a negative correlation between the decrease in SATI and VATI after NT, and both tumor regression and nutritional score. Notably, patients who experienced a significant loss in SATI or VATI post-NT had shorter Recurrence-Free Survival (RFS) and Overall Survival (OS). Additionally, significant loss in SATI and VATI emerged as an independent risk factor for both RFS and OS. In conclusion, our study convincingly demonstrates that in patients with advanced gastric cancer, SATI and VATI decreases after NT and is negatively associated with tumor regression and nutritional score. A significant loss in SATI and VATI is a risk factor for shorter RFS and OS, thereby underscoring the importance of maintaining body composition during NT.

Construction and interpretation of machine learning-based prognostic models for survival prediction among intestinal-type and diffuse-type gastric cancer patients

BackgroundGastric cancer is one of the most common malignant tumors worldwide, with high incidence and mortality rates, and it has a complex etiology and complex pathological features. Depending on the tumor type, gastric cancer can be classified as intestinal-type and diffuse-type gastric cancer, each with distinct pathogenic mechanisms and clinical presentations. In recent years, machine learning techniques have been widely applied in the medical field, offering new perspectives for the diagnosis, treatment, and prognosis of gastric cancer patients.MethodsThis study recruited 2158 gastric cancer patients and constructed prognostic prediction models for both intestinal-type and diffuse-type gastric cancer. Clinical pathological data were collected from patients, and machine learning algorithms were used for feature selection and model construction. The performance of the models was validated with training and testing datasets. The Shapley additive explanations (SHAP) values were used to interpret the model predictions and identify the main factors that influence patient survival.ResultsIn the prognostic model for intestinal-type gastric cancer, the gradient boosting decision tree (GBDT) model demonstrated the best performance, with key features including pTNM, CA125, tumor size, CA199, and PALB. Similarly, in the prognostic model for diffuse-type gastric cancer, the GBDT model was utilized, with key features comprising pTNM, Borrmann type IV disease, lymphocyte (LYM), lactate dehydrogenase (LDH), potassium (K), perineural invasion (PNI), tumor size, and whole stomach location. Risk stratification analysis revealed that the prognosis of high-risk patients was significantly worse than that of low-risk patients.ConclusionMachine learning shows great potential in predicting survival outcomes of gastric cancer patients, providing strong support for the development of personalized treatment plans.

CT Imaging as a Single Modality for Clinical Staging of Gastric Cancer in Limited Resource Centers: A Retrospective Pilot Study.

Gastric cancer disproportionately impacts populations in resource-limited settings. Within a safety-net network, we assessed the utility of computed tomography (CT) as a single staging modality. We utilized a clinical database of gastric cancer patients treated within the Los Angeles County safety-net hospital system from 2016 to 2023 in conjunction with retrospective imaging review by certified radiologists. We assessed agreement between clinical and pathological staging for patients who underwent curative gastrectomy using the Kappa coefficient. Of 107 patients with available CT imaging, 43.9% (n = 47) were staged with CT as a single modality. Most tumors displayed infiltrating (75%) or diffuse (28%) morphology, 41% displayed adequate gastric distention and regional lymphadenopathy was common (68%). Twenty-nine patients underwent curative gastrectomy. Overall agreement was minimal (κ = 0.29, 95% CI [0.071-0.51], p = 0.022), weak for T3/T4 tumors (κ = 0.50, 95% CI [0.17-0.82], p < 0.01), and weak for Hispanic/Latino patients (κ = 0.47, 95% CI [0.19-0.76], p < 0.01). There was minimal agreement between clinical and pathologic staging when assessing clinical stage by CT imaging alone, suggesting that CT is not adequate as a single modality staging tool. While every effort should be made to obtain multimodal staging, larger studies are warranted to improve CT imaging protocols for staging in resource-limited settings.

Pan-cancer analysis of Sp1 with a focus on immunomodulatory roles in gastric cancer

BackgroundSp1, a transcription factor, regulates essential cellular processes and plays important tumorigenic roles across diverse cancers. However, comprehensive pan-cancer analyses of its expression and potential immunomodulatory roles remain unexplored.MethodsUtilizing bioinformatics tools and public datasets, we examined the expression of Sp1 across normal tissues, tumors, and immune cells, and screened for pre- and post-transcriptional modifications, including genetic alterations, DNA methylation, and protein phosphorylation, affecting its expression or function. The association of Sp1 expression with immune cell infiltration, tumor mutational burden, and immune checkpoint signaling was also investigated. Single-cell transcriptome data was used to assess Sp1 expression in immune cells in gastric cancer (GC), and findings were corroborated using immunohistochemistry and multiplex immunofluorescence in an immunotherapy-treated patient cohort. The prognostic value of Sp1 in GC patients receiving immunotherapy was evaluated with Cox regression models.ResultsElevated Sp1 levels were observed in various cancers compared to normal tissues, with notable prominence in GC. High Sp1 expression correlated with advanced stage, poor prognosis, elevated tumor mutational burden (TMB), and microsatellite instability (MSI) status, particularly in GC. Significant correlations between Sp1 levels and CD8+ T cell and the M1 phenotype of tumor-associated macrophages were further detected upon multiplex immunofluorescence in GC samples. Interestingly, we verified that GC patients with higher Sp1 levels exhibited improved response to immunotherapy. Moreover, Sp1 emerged as a prognostic and predictive biomarker for GC patients undergoing immunotherapy.ConclusionsOur pan-cancer analysis sheds light on the multifaceted role of Sp1 in tumorigenesis and underscores its potential as a prognostic and predictive biomarker for patients with GC undergoing immunotherapy.

Perioperative use of enteral nutrition with ω-3 polyunsaturated fatty acid in patients with gastric cancer: a meta-analysis.

To systematically evaluate the efficacy and safety of enteral nutrition with ω-3 polyunsaturated fatty acid preparations or standard enteral nutrition preparations used in patients with gastric cancer during perioperative period, and to provide reference for clinical rational drug use. Pubmed, EMbase, The Cochrane Library, CNKI and Wanfang Medical databases were searched by computer to collect relevant literature. The search period was from the establishment of the database to August 1, 2024. Meta-analysis was performed using Revman5.4 software after two researchers independently screened literature, extracted data, and evaluated the risk of bias in included studies. A total of 20 randomized controlled studies were included. The Meta results showed that there was no statistical difference in mortality between the enteral nutrition with ω-3 polyunsaturated fatty acid group and the control group (RR = 0.46, P = 0.17). However, the IEN group demonstrated superior advantages in reducing infection complications (RR = 0.81, P = 0.05) and wound infection (RR = 0.61, P = 0.04) among gastric cancer patients, as well as improving immune-related indicators (including IgG, IgA, IgM, CD4, and CD4/CD8), inflammation-related markers (including CRP, IL-1β, and IL-6), and nutritional indicators (including Total protein, Albumin, and Transferrin). enteral nutrition with ω-3 polyunsaturated fatty acid preparation has advantages in the efficacy and safety of perioperative nutritional therapy in patients with gastric cancer, and can be used as a clinical choice. Due to the limited number and quality of included studies, the above conclusions need to be verified by more high-quality studies.

Integrin β5, a noninvasive diagnostic biomarker, is associated with unfavorable prognosis and immunotherapy efficacy in gastric cancer

BackgroundIntegrin β5 (ITGB5) is a pivotal player in the pathogenesis of gastric cancer (GC). We aimed to explore the potential value of ITGB5 as a predictor of diagnosis and immunotherapy in gastric cancer.MethodsThe expression of ITGB5 in GC was assessed using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and verified through quantitative polymerase chain reaction (qPCR) and immunohistochemistry. Kaplan-Meier curves were conducted to evaluate the prognostic significance. The immune cells infiltration, tumor mutational burden (TMB), and immunophenoscore (IPS) were examined using CIBERSORT, TIMER, and TISIDB. In addition, colony formation, scratch assays, and transwell assays were employed to determine the impact on tumor progression and metastasis. CD276 expression was detected by western blotting following the knockdown of ITGB5. ELISA was utilized to measure serum ITGB5 levels.ResultsThe expression of ITGB5 in GC tissue surpassed that in normal tissue, it might contribute to GC pathogenesis through pathways including PI3K-AKT, ECM-receptor interaction, and TGF-beta. The elevated ITGB5 expression is associated with poor prognosis in GC patients. In addition, a strong positive association between ITGB5 overexpression and the infiltration levels of macrophages and monocytes, and it significantly influenced immune response. Moreover, lower expression of ITGB5 was associated with better immunotherapy efficacy. Subsequent investigation demonstrated that silencing of ITGB5 suppressed the proliferation and migration of GC cell lines in vitro. ITGB5 expression was positively correlated with CD276 expression and the knockdown of ITGB5 resulted a notable decrease CD276 expression. Futhermore, a significantly high level of serum ITGB5 was observed in GC patients. The combined assessment of ITGB5, CEA, and CA19-9 improved the diagnostic accuracy.ConclusionsITGB5 potentially serve as both a diagnostic biomarker and therapeutic target in managing GC.

MicroRNA-582-5p inhibits the progression of gastric cancer cells and their resistance to oxaliplatin by suppressing ATG7 expression.

Gastric cancer (GC) is one of the most common malignant tumors of the digestive tract worldwide. Both environmental and genetic factors contribute to the occurrence and development of GC. Surgery and chemotherapy are the main treatment modalities for gastric cancer; however, some patients show insensitivity to chemotherapeutic agents. Chemotherapy resistance is one of the primary reasons for poor treatment outcomes and the high likelihood of recurrence and metastasis in gastric cancer patients. Numerous studies have confirmed a correlation between the dysregulation of microRNA expression and the development of various malignant tumors, as well as their resistance to chemotherapeutic agents. However, the role of microRNA-582-3p in gastric cancer cells and its mechanism in the resistance of gastric cancer cells to oxaliplatin have not been studied. We first used q-PCR, CCK8, transwell, and scratch assays to validate the expression of microRNA-582-3p in gastric cancer tissues and cells, while also analyzing the relationship between its expression levels and the clinical pathological data of patients. Additionally, we further confirmed the impact of microRNA-582-3p on gastric cancer cell progression and oxaliplatin resistance through knockdown and overexpression experiments. Subsequently, to explore the specific mechanisms of microRNA-582-3p in gastric cancer, we verified the downstream target of microRNA-582-3p, ATG7, using dual-luciferase reporter assays and examined the effect of ATG7 on gastric cancer cell functions. Moreover, we conducted rescue experiments to further validate the interaction between microRNA-582-3p and ATG7. Our experimental results confirmed that microRNA-582-3p is lowly expressed in gastric cancer tissues and cells, and the expression level of miR-582-5p is correlated with the T stage of patients, while showing no correlation with the patients' gender, age, tumor size, degree of differentiation, or N stage. Additionally, we found that microRNA-582-3p functions as a tumor suppressor in gastric cancer cells, as its overexpression inhibits the biological functions of gastric cancer cells and increases their sensitivity to oxaliplatin. Furthermore, we identified binding sites between microRNA-582-3p and the autophagy-related gene ATG7, observing that knockdown of microRNA-582-3p increases ATG7 expression, while its overexpression reduces ATG7 levels. Moreover, ATG7 is overexpressed in gastric cancer cells; knockdown of ATG7 inhibits the biological functions of gastric cancer cells and increases their sensitivity to oxaliplatin, whereas overexpression of ATG7 reverses the inhibitory effect of miR-582-5p on gastric cancer. Our study confirms that microRNA-582-3p acts as a tumor suppressor in gastric cancer cells, and its role may be mediated through the regulation of ATG7 expression levels. MicroRNA-582-3p may serve as a potential target for gastric cancer treatment and a predictive biomarker.

A CXCR4 partial agonist improves immunotherapy by targeting polymorphonuclear myeloid-derived suppressor cells and cancer-driven granulopoiesis.

Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) are pathologically activated neutrophils that potently impair immunotherapy responses. The chemokine receptor CXCR4, a central regulator of hematopoiesis, represents an attractive PMN-MDSC target1. Here, we fused a secreted CXCR4 partial agonist TFF2 to mouse serum albumin (MSA) and demonstrated that TFF2-MSA peptide synergized with anti-PD-1 to induce tumor regression or eradication, inhibited distant metastases, and prolonged survival in multiple gastric cancer (GC) models. Using histidine decarboxylase (Hdc)-GFP transgenic mice to track PMN-MDSC in vivo , we found TFF2-MSA selectively reduced the immunosuppressive Hdc-GFP + CXCR4 hi tumor PMN-MDSCs while preserving proinflammatory neutrophils, thereby boosting CD8 + T cell-mediated anti-tumor response together with anti-PD-1. Furthermore, TFF2-MSA systemically reduced PMN-MDSCs and bone marrow granulopoiesis. In contrast, CXCR4 antagonism plus anti-PD-1 failed to provide a similar therapeutic benefit. In GC patients, expanded PMN-MDSCs containing a prominent CXCR4 + LOX-1 + subset are inversely correlated with the TFF2 level and CD8 + T cells in circulation. Collectively, our studies introduce a strategy of using CXCR4 partial agonism to restore anti-PD-1 sensitivity in GC by targeting PMN-MDSCs and granulopoiesis.

Predictive value of prognostic nutritional index in patients undergoing gastrectomy for gastric cancer: A systematic review and meta-analysis.

The value of prognostic nutritional index (PNI) in gastrectomy remains controversial. This meta-analysis aimed to evaluate the predictive value of PNI in patients undergoing gastrectomy for malignancy. We retrieved studies from medical literature databases to analyze the endpoints of overall survival, cancer-specific survival, recurrence-free survival, and clinicopathologic features. The hazard ratio (HR) and 95% confidence interval (CI) were used to access the survival prognostic value of PNI in patients after gastrectomy. Odds ratio and mean difference were used to evaluate the relationship between the low PNI and clinicopathologic features. In total, we included 38 articles (39 trial comparisons) which contained 23,756 gastrectomy patients. The results showed that low PNI was associated with shorter overall survival (HR: 1.82, 95% CI 1.62-2.03), shorter cancer-specific survival (HR: 1.44, 95% CI 1.24-1.67), and shorter recurrence-free survival (HR: 2.52, 95% CI 1.41-4.47). Besides, patients with low PNI had a higher risk of postoperative complications compared with high PNI (HR: 1.65, 95% CI 1.30-2.09). And low PNI group was found to be related to older, lower BMI, larger tumor size, deeper tumor invasion, poorer differentiation, more advanced tumor stage, total gastrectomy, and the presence of lymph node metastasis, lymphatic invasion, and vessel invasion. PNI was significantly associated with survival and postoperative complications of gastric cancer patients undergoing gastrectomy. Therefore PNI has the potential to be a prognostic predictor for gastrectomy.

Gastric Cancer Actively Remodels Mechanical Microenvironment to Promote Chemotherapy Resistance via MSCs-Mediated Mitochondrial Transfer.

Chemotherapy resistance is the main reason of treatment failure in gastric cancer (GC). However, the mechanism of oxaliplatin (OXA) resistance remains unclear. Here, we demonstrate that extracellular mechanical signaling plays crucial roles in OXA resistance within GC. We selected OXA-resistant GC patients and analyzed tumor tissues by single-cell sequencing, and found that the mitochondrial content of GC cells increased in a biosynthesis-independent manner. Moreover, we found that the increased mitochondria of GC cells were mainly derived from mesenchymal stromal cells (MSCs), whichcould repair the mitochondrial function and reduce the levels of mitophagy in GC cells, thus leading to OXA resistance. Furthermore, we investigated the underlying mechanism and found that mitochondrial transfer was mediated by mechanical signals of the extracellular matrix (ECM). After OXA administration, GC cells actively secreted ECM in the tumor microenvironment (TEM), increasing matrix stiffness of the tumor tissues, which promoted mitochondria to transfer from MSCs to GC cells via microvesicles (MVs). Meanwhile, inhibiting the mechanical-related RhoA/ROCK1 pathway could alleviate OXA resistance in GC cells. In summary, these results indicate that matrix stiffness could be used as an indicator to identify chemotherapy resistance, and targeting mechanical-related pathway could effectively alleviate OXA resistance and improve therapeutic efficacy.

Granzyme B PET/CT Imaging Evaluates Early Response to Immunotherapy in Gastric Cancer.

In several malignancies, only a limited number of patients respond to immune checkpoint inhibitors. Predicting and monitoring responses to these inhibitors represent an unmet clinical need. Here, we developed a PET/CT probe targeting granzyme B, [68Ga]Ga-NOTA-Gly-Gly-Gly-Ile-Glu-Pro-Asp-CHO (GSI), and aimed to investigate whether it can be used to monitor the effects of immune checkpoint inhibitors early in the course of therapy. Methods: Seventy-two patients with gastric cancer (stages III-IV) were recruited for [68Ga]Ga-DOTA-GSI PET/CT imaging after 2 or 3 cycles of the immunotherapy, and 40 patients were included in the final analysis. The SUVmax of primary tumors (SUVmax-t), SUVmax of metastatic lymph nodes (SUVmax-LN), and SUVmax of normal tissues (liver and blood pool) were measured, and their target-to-liver background ratio (TLR) and target-to-blood background ratio (TBR) were denoted for primary tumors as TLRtumor and TBRtumor and for metastatic lymph nodes as TLRLN and TBRLN, respectively. The treatment responses were assessed within 1 wk after full-course treatment according to RECIST version 1.1. Wilcoxon rank-sum tests were used to compare the PET/CT parameters between responders and nonresponders. Receiver operating characteristic curve analysis was used to assess the diagnostic efficacy of [68Ga]Ga-DOTA-GSI PET/CT parameters in identifying responders. Two-tailed P value of less than 0.05 was considered statistically significant. Results: We found that SUVmax-t, TLRtumor, TBRtumor, SUVmax-LN, and TBRLN were higher in responders than in nonresponders (2.49 ± 0.58 vs. 1.55 ± 0.48, P = 0.000; 2.24 ± 0.48 vs. 1.74 ± 0.67, P = 0.007; 1.38 ± 0.43 vs. 0.90 ± 0.23, P = 0.000; 2.24 ± 0.99 vs. 1.42 ± 0.55, P = 0.003; and 1.28 ± 0.68 vs. 0.83 ± 0.32, P = 0.012, respectively). According to receiver operating characteristic curve analysis, the area under the curve for SUVmax-t, TBRtumor, TLRtumor, SUVmax-LN, TLRLN, and TBRLN was 0.886, 0.866, 0.746, 0.772, 0.648, and 0.731, respectively. The threshold of SUVmax-t was 2.05, and its sensitivity and specificity were 81.0% and 84.2%, respectively. In addition, multivariate logistic regression indicated that TBRtumor was an independent predictor of treatment response (P = 0.03). Conclusion: Our results indicated that [68Ga]Ga-DOTA-GSI PET/CT is a promising tool for predicting early response to combined immunotherapy in gastric cancer patients.

Long non-coding RNA AC010457.1 promotes the growth and EMT of gastric cancer via the PI3K/AKT axis

Gastric cancer (GC) is a malignancy with a relatively high mortality rate. This study aimed to ascertain the prognostic significance of long non-coding RNA (lncRNA) AC010457.1 in GC and elucidate its role in disease progression. The Cancer Genome Atlas (TCGA) database was used to screen the prognosis-associated differentially expressed lncRNAs in GC patients. Kaplan-Meier curves, univariate and multivariate Cox regression analyses were applied to assess the prognostic significance of AC010457.1. In vitro and in vivo functional assays were performed to evaluate the effects of AC010457.1 on cellular proliferation and metastasis. Mechanistic investigations, including Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, Western blotting (WB), Immunofluorescence (IF), and Immunohistochemistry (IHC), were used to explore the signaling pathways activated by AC010457.1. We demonstrated that AC010457.1 was abnormally upregulated in GC tissues, and that this aberrant upregulation was associated with a poor prognosis for GC patients. The functional experiments proved that the downregulated of AC010457.1 hindered GC cell proliferation, migration, and invasive potential. Furthermore, KEGG analysis revealed a significant association between AC010457.1 and the PI3K/AKT signaling pathway, which was further corroborated by WB analysis. Rescue experiments provided additional confirmation that AC010457.1 regulated PI3K/AKT promote GC proliferation, migration, and epithelial-mesenchymal transition (EMT). Collectively, our findings suggest that AC010457.1 overexpression serves as a distinct prognostic risk factor in GC and may represent a promising therapeutic target for the treatment of this malignancy.

Esophagojejunostomy using a circular stapler vs. a linear stapler for gastric cardia cancer patients: impact of upper margin length and tumor size on the survival rate.

The incidence of gastric cancer is concomitantly rising with gastric cardia cancer worldwide. While the improvement of gastric cancer surgical techniques is glowing, this study assesses the impact of the upper margin length and tumor size on the survival rate for gastric cardia cancer patients who underwent total laparoscopic total gastrectomy(TLTG) or laparoscopic assisted total gastrectomy(LATG). A total of 63 patients with gastric cardia cancer who underwent laparoscopic total gastrectomy were retro-prospectively collected from January 2021 to May 2023. While assessing the impact of upper margin length and tumor size on the survival rate, esophagojejunostomy using a linear stapler has been compared to a circular stapler. The sixty-three patients met inclusion criteria; 32 (51%) underwent LATG and 31 (49%) underwent TLTG. Their mean age was 65 years (range, 45-77). The blood loss means in LATG and TLTG was 74.69 and 50.16 ml, respectively (p = 0.005), and surgery duration was higher in LATG than LATG with respective means of 247 min and 222.42 min. (p = 0.006). However, the tumor size means (p = 0.5), and upper margin length means (p = 0.052) were not significantly different in the LATG and TLTG groups, respectively. The number of resected and assessed lymph node was adequate in the LATG and TLTG groups. The current study still does not find an independent related risk from the upper margin length and tumor size to the survival rate according to the multiple regression analysis (p = 0.080). The upper margin length and tumor size do not have a relationship with the survival rate of the compared esophagojejunostomy (EJS) methods. The EJS using a linear stapler requires a shorter surgery duration and less blood loss than EJS using a circular stapler.

Vitamin B12 Intake and Cancer Risk: Findings from a Case-Control Study in Vietnam

There is inconclusive evidence on the role of dietary intake of vitamin B12 in cancer. We evaluated the association between vitamin B12 intake and cancer risk in a hospital-based case-control study, comprising 3,758 cancer cases and 2,995 controls in Vietnam. Vitamin B12 intake was derived from the validated food frequency questionnaire. Unconditional logistic regression model was used to calculate the odds ratios (ORs), and respective 95% confidence intervals (CIs) for the association between vitamin B12 and cancer risk. There was a U-shaped association between vitamin B12 intake and overall risk of cancer. Individuals with intakes lower than the median intake had a 6% (OR = 1.06, 95% CI: 0.86–1.31)-107% (OR = 2.07, 95% CI: 1.58–2.71), increased risk of cancer (Ptrend <0.001), whereas those with higher intakes than the median intake had a 20% (OR = 1.20, 95% CI: 0.97–1.48)-52% (OR = 1.52, 95% CI: 1.22–1.89) increased risk of cancer (Ptrend <0.04). The excess risk of cancer associated with low intakes of vitamin B12 was observed among esophageal, lung, and breast cancer patients, whereas with high intakes of vitamin B12 among gastric cancer patients. In summary, a U-shaped association between vitamin B12 intake and increased cancer risk was observed in the Vietnamese population.

Enantiospecific profiling of D-amino acid for gastric cancer diagnosis by using a biocatalytic MHOF nanoreactor

The dynamic variation of D-amino acids (D-AAs) in human saliva has great potential as the indicator for individual physiological states and disease progression; however, enantiospecific profiling of D-AAs is a great challenge. In this work, a nanoreactor based on mesoporous hydrogen-bonded organic framework (MHOF) has been fabricated for the enantiospecific profiling of D-AAs. The nanoreactor is prepared by using MHOFs as the scaffold to organize the biocatalytic cascade of D-AA oxidase (DAAO) and horseradish peroxidase (HRP). In the meanwhile, the large, stable, and robust transport channels of MHOFs allow the unimpeded transport of the involved biocatalytic substrates. Once D-AA substrates efficiently transport into MHOFs, the chromogenic reactions of 3,3′,5,5′-tetramethylbenzidine (TMB) and H2O2 can be activated. So, using this MHOF nanoreactor, enantiospecific and visual detection of D-AAs can be achieved. Moreover, the stable nanoreactor can be operated in complex solution and utilized for the profiling of D-AA levels in saliva samples collected from gastric cancer patients, suggesting that D-AAs may be a powerful fingerprint for the diagnosis of gastric cancer. Therefore, the fabricated MHOF-based nanoreactor may provide an emerging tool for the enantiospecific profiling of D-AAs and supports the D-AA fingerprint as the indicator of gastric cancer diagnosis.

GDF15 enhances anoikis resistance and metastasis of gastric cancer through protective autophagy

Distant metastasis is a prevalent cause of mortality in gastric cancer (GC) patients. Anoikis, a process that induces cell death when cells get detached from the extracellular matrix (ECM), acts as a barrier to tumor metastasis. To survive in the circulatory system and metastasize, tumor cells must acquire anoikis resistance. It is crucial to identify the molecular processes that cause resistance to anoikis in GC since this might lead to the discovery of novel treatment targets and improve the long-term survival of GC patients. In this study, we employed quantitative proteomics to identify growth differentiation factor 15 (GDF15) as a key factor in GC anoikis resistance. We found that GDF15 enhances protective autophagy, thereby promoting anoikis resistance in GC cells. Furthermore, through DNA pull down assay, activating transcription factor 2 (ATF2) was found to be a critical regulator of GDF15 expression, acting as a transcriptional activator of GDF15. Collectively, these discoveries indicate that ATF2 and GDF15 have great potential as target candidates for developing therapeutic strategies to address the metastasis of GC.

Development and Validation of a Computed Tomography-Based Model for Noninvasive Prediction of the T Stage in Gastric Cancer: Multicenter Retrospective Study.

As part of the TNM (tumor-node-metastasis) staging system, T staging based on tumor depth is crucial for developing treatment plans. Previous studies have constructed a deep learning model based on computed tomographic (CT) radiomic signatures to predict the numberoflymphnodemetastases and survival in patients with resected gastric cancer (GC). However, few studies have reported the combination of deep learning and radiomics in predicting T staging in GC. This study aimed to develop a CT-based model for automatic prediction of the T stage of GC via radiomics and deep learning. A total of 771 GC patients from 3 centers were retrospectively enrolled and divided into training, validation, and testing cohorts. Patients with GC were classified into mild (stage T1 and T2), moderate (stage T3), and severe (stage T4) groups. Three predictive models based on the labeled CT images were constructed using the radiomics features (radiomics model), deep features (deep learning model), and a combination of both (hybrid model). The overall classification accuracy of the radiomics model was 64.3% in the internal testing data set. The deep learning model and hybrid model showed better performance than the radiomics model, with overall classification accuracies of 75.7% (P=.04) and 81.4% (P=.001), respectively. On the subtasks of binary classification of tumor severity, the areas under the curve of the radiomics, deep learning, and hybrid models were 0.875, 0.866, and 0.886 in the internal testing data set and 0.820, 0.818, and 0.972 in the external testing data set, respectively, for differentiating mild (stage T1~T2) from nonmild (stage T3~T4) patients, and were 0.815, 0.892, and 0.894 in the internal testing data set and 0.685, 0.808, and 0.897 in the external testing data set, respectively, for differentiating nonsevere (stage T1~T3) from severe (stage T4) patients. The hybrid model integrating radiomics features and deep features showed favorable performance in diagnosing the pathological stage of GC.

Perioperative systemic and prophylactic intraperitoneal chemotherapy for type 4/large type 3 gastric cancer: DRAGON-10.

Large type 3 and type 4 gastric cancers (GC) have a significantly poor prognosis, primarily due to their high predisposition for peritoneal dissemination. The application of intraperitoneal chemotherapy has emerged as a viable therapeutic strategy for managing GC patients with peritoneal metastasis. This study is planned to enroll 37 resectable large type 3 or type 4 GC patients. These patients are scheduled to undergo a treatment comprising preoperative chemotherapy with paclitaxel, oxaliplatin and S-1, followed by D2 gastrectomy, and concluding with postoperative treatments that include prophylactic intraperitoneal chemotherapy. The study's primary objective is to evaluate the 3-year peritoneal recurrence rate. Secondary objectives are to assess the 3-year disease-free survival, 3-year overall survival and to monitor the adverse events.Clinical trial registration number: ChiCTR2400083253 (https://www.chictr.org.cn).

Identification of plasma exosomal lncRNA as a biomarker for early diagnosis of gastric cancer.

There were about 1,090,000 gastric cancer (GC) cases in 2020 in China. The incidence and mortality rates ranked the fifth and third among all kinds of cancers in China. Early diagnosis plays an important role in the treatment and prognosis of gastric cancer. In recent years, noninvasive diagnosis, especially plasma exosome lncRNAs, has become a promissing biomarkers with high specificity and sensitivity for early diagnosis of cancers. In this study, plasma exosomes of patients with early gastric cancer were extracted efficiently by affinity membrane separation technology, including affinity adsorption, elution, affinity membrane regeneration and other steps. After identified by electron microscopy observation, particle size analysis and Western blot verification, the lncRNAs in the exosomes were extracted and were analysized by high-throughput RNA sequencing (RNA-Seq). The differentially expressed lncRNAs were verified by RT-qPCR in 93 patients with early gastric cancer and 49 normal controls. Electron microscopy, particle size analysis and Western blot showed that exosomes were successfully isolated from plasma. RNA-Seq results show that 76 lncRNAs were upregulated and 260 lncRNAs were downregulated in plasma exosomes of early gastric cancer patients compared with normal controls. RT-qPCR analysis indicated that a total of 6 lncRNAs were significantly and differentially expressed in gastric cancer patients compared to normal controls, with 2 (lncmstrg. 1319590, Lncmstrg. 2312697) highly expressed and 4 lowly expressed (lncmstr-g.1004024.1, lncmstrg. 2441832.8, lncmstrg. 315376.1, lncmstrg.907985.2,) (p < 0.05). The survival curve analysis indicated that lncmstrg.2441832.8 and lncmstrg.2312697 had higher sensitivity and specificity for the diagnosis of gastric cancer, respectively and AUC curve areas were 0.6211 and 0.631, p < 0.05, respectively, which were greater than the traditional clinical detection indexes CEA (0.61) and AFP (0.57). When combined lncmstrg.2441832.8 and lncmstrg.2312697 in gastric cancer diagnosis, AUC curve area reached 0.73, which was greater than CA199 (0.71). Lncmstrg.2441832.8 and lncmstrg.2312697 may be a potential and promissing biomarkers for early diagnosis of gastric cancer.