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The interaction between cancer cells and immune cells plays critical roles in gastric cancer (GC) progression and immune evasion. Forced legumain (LGMN) is one of the characteristics correlated with poor prognosis in gastric cancer patients. However, the role of gastric-cancer-secreted LGMN (sLGMN) in modulating the tumor immune microenvironment and the biological effect on the immune evasion of gastric cancer remains unclear. In this study, we found that forced expression of sLGMN in gastric cancer serum correlates with increased M2 macrophage infiltration in GC tissues and predicted resistance to anti-PD-1 immunotherapy. Mechanistically, gastric cancer cells secrete LGMN via binding to cell surface Integrin αvβ3, then activate Integrin αvβ3/PI3K (Phosphatidylinositol-4,5-bisphosphate3-kinase)/AKT (serine/threonine kinase)/mTORC2 (mammalian target of rapamycin complex 2) signaling, promote metabolic reprogramming, and polarize macrophages from the M1 to the M2 phenotype. Either blocking LGMN, Integrin αv, or knocking out Integrin αv expression and abolishing the LGMN/Integrin αvβ3 interaction significantly inhibits metabolic reprogramming and polarizes macrophages from the M1 to the M2 phenotype. This study reveals a critical molecular crosstalk between gastric cancer cells and macrophages through the sLGMN/Integrinαvβ3/PI3K/AKT/mTORC2 axis in promoting gastric cancer immune evasion and resistance to anti-PD-1 immunotherapy, indicating that the sLGMN/Integrinαvβ3/PI3K/AKT/mTORC2 axis may act as a promising therapeutic target. [ABSTRACT FROM AUTHOR]

Objective: To explore the correlation between coronary heart disease related genes and coronary heart disease in hospitalized patients in Hainan, and to provide theoretical basis for enriching the screening methods of high-risk groups of coronary heart disease in Hainan, and optimizing the prevention and treatment strategies. Methods: We select hospitalized patients born in Hainan and aged >30 years old from the Second Affiliated Hospital of Hainan Medical Unversity between January 1, 2020 and June 30, 2022, and divided the patients into the coronary heart disease group and the non-coronary heart disease group. PCR real-time fluorescence was used to measure gene expression, and Spearman correlation analysis was used to explore the correlation between gene expression and coronary heart disease. Results: A total of 55 whole blood samples were collected from non-coronary heart disease patients (including 26 women and 29 men), with a median age of 57 years, and 170 whole blood samples from coronary heart disease patients (including 44 women and 126 men), with a median age of 63.17. Apolipoprotein B gene (ApoB) was highly expressed in patients with coronary heart disease (P<0.001); AGT gene (P=0.015 8), ApoE gene (P=0.012 6), FGB gene (P=0.005), GNB gene (P=0.015 1), MTFHR gene (P=0.011 9), SEL gene (P=0.005), TNF gene (P=0.029 8) were significantly overexpressed in the non-coronary heart disease group. The expression of NOS3 gene (P=0.304 7), IL6 gene (P=0.723 9), ACE gene (P=0.785 2)was not different between the two groups. Coronary heart disease was negatively correlated with AGT gene (r=-0.163, P=0.011, P<0.05), positively correlated with APOB gene(r=0.75, P=0, P<0.01), negatively correlated with FGB gene(r=-0.163, P=0.011, P<0.05), negatively correlated with GNB gene(r=-0.165, P=0.011, P<0.05), negatively correlated withSEL gene(r=-0.171, P=0.007, P<0.01), negatively correlated with MHTHR gene(r=-0.210, P=0.001, P<0.01) and negatively correlated with TNF gene(r=-0.131, P=0.04, P<0.05), but coronary heart disease was not correlated with APOE, NOS3, ACE, IL6 and other genes (P>0.05). The ApoB gene of coronary heart disease was negatively correlated with triglyceride (r=-0.461, P=0), positively correlated with age (r=0.173, P=0.009), positively correlated with total cholesterol (r=0.499, P=0), negatively correlated with high-density lipoprotein (r=-0.181, P=0.007), and negatively correlated with low-density lipoprotein (r=-0.143, P=0.031). Conclusion: (1) The detection of apolipoprotein B gene expression may be used as an indicator for screening coronary heart disease in the coronary population in Hainan. It may increase the risk of coronary heart disease by affecting the level of total cholesterol. A larger sample of research is still needed.(2) AGT,ApoE, FGB, GNB, MTFHR, SELE, TNF and other genes may be the protective genes of non-coronary heart disease population in Hainan, and the high expression of these genes may reduce the occurrence of coronary heart disease, which still needs further study. [ABSTRACT FROM AUTHOR]

Background: Accurate estimation of the recurrence of pancreatic neuroendocrine tumors help with prognosis, guide follow-up, and avoid futile treatments.Purpose: To investigate whether MRI features could preoperatively estimate the recurrence of pancreatic neuroendocrine tumors (PNETs) and to refine a novel prognostic model through developing a nomogram incorporating various MRI features.Study Type: Retrospective.Population: In all, 81 patients with clinicopathologically confirmed nonmetastatic PNETs.Field Strength/sequences: 1.5 T MR, including T1 -weighted, T2 -weighted, and diffusion-weighted imaging sequences.Assessment: Qualitative and quantitative MRI features of PNET were assessed by three experienced radiologists.Statistical Tests: Uni- and multivariable analyses for recurrence-free survival (RFS) were evaluated using a Cox proportional hazards model. The MRI-based nomogram was then designed based on multivariable logistic analysis in our study and the performance of the nomogram was validated according to C-index, calibration, and decision curve analyses.Results: MRI features, including tumor size (hazard ratio [HR]: 14.131; P = 0.034), enhancement pattern (HR: 21.821, P = 0.032), and the apparent diffusion coefficient (ADC) values (HR: 0.055, P = 0.038) were significant independent predictors of RFS at multivariable analysis. The performance of the nomogram incorporating various MRI features (with a C-index of 0.910) was improved compared with that based on tumor size, enhancement pattern, and ADC alone (with C-index values of 0.672, 0.851, and 0.809, respectively). The calibration curve of the nomogram exhibited perfect consistency between estimation and observation at 0.5, 1, and 2 years after surgery. The decision curve showed that a nomogram incorporating three features had more favorable clinical predictive usefulness than any single feature.Data Conclusion: MRI features can be considered effective recurrence predictors for PNETs after surgery. The preliminary nomogram incorporating various MRI features could assess the risk of recurrence in PNETs and may be used to optimize individual treatment strategies.Level Of Evidence: 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:397-409. [ABSTRACT FROM AUTHOR]

Objectives: Tumour cell proliferation requires high metabolism to meet the bioenergetics and biosynthetic needs. Dauer in Caenorhabditis elegans is characterized by lower metabolism, and we established an approach with C elegans to find potential tumour therapy targets. Materials and methods: RNAi screening was used to find dauer‐related genes, and these genes were further analysed in glp‐1(−) mutants for tumour‐suppressing testing. The identified tumour‐related genes were verified in clinical tumour tissues. Results: The lifespan of glp‐1(−) mutants was found to be extended by classical dauer formation signalling. Then, 61 of 287 kinase‐coding genes in Caenorhabditis elegans were identified as dauer‐related genes, of which 27 were found to be homologous to human oncogenes. Furthermore, 12 dauer‐related genes were randomly selected for tumour‐suppressing test, and six genes significantly extended the lifespan of glp‐1(−) mutants. Of these six genes, F47D12.9, W02B12.12 and gcy‐21 were newly linked to dauer formation. These three new dauer‐related genes significantly suppressed tumour cell proliferation and thus extended the lifespan of glp‐1(−) mutants in a longevity‐ or dauer‐independent manner. The mRNA expression profiles indicated that these dauer‐related genes trigged similar low metabolism pattern in glp‐1(−) mutants. Notably, the expression of homolog gene DCAF4L2/F47D12.9, TSSK6/W02B12.12 and NPR1/gcy‐21 was found to be higher in glioma compared with adjacent normal tissue. In addition, the high expression of TSSK6/W02B12.12 and NPR1/gcy‐21 correlated with a worse survival in glioma patients. Conclusions: Dauer gene screening in combination with tumour‐suppressing test in glp‐1(−) mutants provided a useful approach to find potential targets for tumour therapy via suppressing tumour cell proliferation and rewiring tumour cell metabolism. [ABSTRACT FROM AUTHOR]