Background: The application of machine learning (ML) for identifying early gastric cancer (EGC) has drawn increasing attention. However, there lacks evidence-based support for its specific diagnostic performance. Hence, this systematic review and meta-analysis was implemented to assess the performance of image-based ML in EGC diagnosis. Methods: We performed a comprehensive electronic search in PubMed, Embase, Cochrane Library, and Web of Science up to September 25, 2022. QUADAS-2 was selected to judge the risk of bias of included articles. We did the meta-analysis using a bivariant mixed-effect model. Sensitivity analysis and heterogeneity test were performed. Results: Twenty-one articles were enrolled. The sensitivity (SEN), specificity (SPE), and SROC of ML-based models were 0.91 (95% CI: 0.87–0.94), 0.85 (95% CI: 0.81–0.89), and 0.94 (95% CI: 0.39–1.00) in the training set and 0.90 (95% CI: 0.86–0.93), 0.90 (95% CI: 0.86–0.92), and 0.96 (95% CI: 0.19–1.00) in the validation set. The SEN, SPE, and SROC of EGC diagnosis by non-specialist clinicians were 0.64 (95% CI: 0.56–0.71), 0.84 (95% CI: 0.77–0.89), and 0.80 (95% CI: 0.29–0.97), and those by specialist clinicians were 0.80 (95% CI: 0.74–0.85), 0.88 (95% CI: 0.85–0.91), and 0.91 (95% CI: 0.37–0.99). With the assistance of ML models, the SEN of non-specialist physicians in the diagnosis of EGC was significantly improved (0.76 vs 0.64). Conclusion: ML-based diagnostic models have greater performance in the identification of EGC. The diagnostic accuracy of non-specialist clinicians can be improved to the level of the specialists with the assistance of ML models. The results suggest that ML models can better assist less experienced clinicians in diagnosing EGC under endoscopy and have broad clinical application value.

In recent years, the involvement of E3 ubiquitin ligase constitutive photomorphogenesis 1 (COP1) in the tumorigenesis of gastric cancer (GC) has been elucidated. However, the exact underlying mechanism remains to be clarified. In the present study, the expression profiles of COP1 in GC were derived from the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) databases, followed by verification via immunohistochemical staining (IHC), Western blotting (WB), and quantitative real‐time polymerase chain reaction (qRT‐PCR) reaction assays on clinical samples. In vitro, the gain‐ and loss‐of‐function experiments of COP1 protein were conducted to explore its role in GC cell lines HGC‐27 and SGC‐7901. Furthermore, we screened the interaction protein of COP1 by yeast two‐hybrid experiment and verified their combination by co‐immunoprecipitation (co‐IP). We preliminary explored the possible underlying mechanisms of COP1 protein in GC cell lines via WB. COP1 was upregulated in GC tissues compared with the corresponding non‐carcinoma tissues. In vitro, the upregulation of COP1 protein promoted the proliferation and migration of GC cells. The yeast two‐hybrid experiment and co‐IP indicated that Cadherin 18 (CDH18) could constitute a complex with COP1. Moreover, cells with COP1 over‐expression showed low levels of CDH18 expression, with the intracellular PI3K/AKT pathway activated and the malignancy of GC cell lines enhanced. Our findings demonstrated that COP1 promoted the GC tumorigenesis by downregulated CDH18 with the involvement of PI3K/AKT signaling pathway in cell lines, suggesting the potential of COP1 as a prognostic biomarker and therapeutic target for GC.

Nerve injury causes hyperexcitability of the dorsal root ganglion (DRG) and spinal dorsal horn (DH) neurons, which results in neuropathic pain. We have previously demonstrated that partial dorsal rhizotomy (PDR) produced less severe pain-like behavior than chronic constriction injury (CCI) or chronic compression of DRG (CCD) and did not enhance DRG neuronal excitability. However, the mechanisms underlying such discrepancy remain unclear. This study was designed to compare the activation of phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2) in DRG and DH, and c-Fos in DH following treatments of CCI, CCD, and PDR. We confirmed that thermal hyperalgesia produced by PDR was less severe than that produced by CCI or CCD. We showed that pERK1/2 in DRG and DH was greatly activated by CCI or CCD, whereas PDR produced only transient and mild pERK1/2 activation. CCI, CCD, and PDR induced robust c-Fos expression in DH; nevertheless, c-Fos⁺ neurons following PDR were much fewer than that following CCI or CCD. Blocking retrograde axonal transport by colchicine proximal to the CCI injury site diminished thermal hyperalgesia and inhibited pERK1/2 and c-Fos activation. These findings demonstrate that less severe pain-like behavior produced by PDR than CCI or CCD attributes to less activation of pERK1/2 and c-Fos. Such neurochemical activation partially relies on retrograde axonal transport of certain “injury signals” from the peripheral injured site to DRG somata.

The immunosuppressive tumor microenvironment remains a major barrier to effective immunotherapy in gastric cancer. In this study, we identified the E3 ubiquitin ligase BFAR as a critical regulator of neutrophil-mediated immune evasion through the S100A8/A9–BFAR–PRP19–YBX1 signaling axis. Multiomics analyses revealed that BFAR is overexpressed in gastric cancer and correlates with poor prognosis. Functional studies demonstrated that BFAR knockdown suppressed tumor growth by reducing neutrophil infiltration and immunosuppressive reprogramming to restore CD8+ T-cell function. Mechanistically, BFAR mediated K48-linked ubiquitination and degradation of PRP19, leading to stabilization of the oncoprotein YBX1, which transcriptionally upregulated neutrophil-recruiting chemokines CXCL1/CXCL3. Infiltrating neutrophils secreted S100A8/A9, which activated NF-κB to induce BFAR expression in tumor cells and created a feed-forward loop that sustains an immunosuppressive tumor microenvironment. Furthermore, BFAR promoted neutrophil PD-L1 expression via GM-CSF, reinforcing T-cell exhaustion. Clinically, BFAR expression correlated with neutrophil infiltration and poor response to anti–PD-1 therapy, whereas its inhibition synergizes with immune checkpoint blockade in preclinical models. Our work unveils BFAR as a central orchestrator of neutrophil-driven immunosuppression and proposes targeting this axis to enhance immunotherapy efficacy in gastric cancer.