Single-cell omics routinely profile millions of cells across the transcriptome and the epigenome. However, embeddings used for clustering, trajectory inference, and visualization remain unstable: stochastic variational autoencoders inject sampling noise at inference, and methods reported on idiosyncratic cohorts defeat head-to-head comparison. We introduce scCCVGBen, a benchmark of single-cell representation-learning methods. Its reference configuration is a centroid-coupled variational graph autoencoder built from three design choices: the centroid (deterministic posterior mean) used as the inference embedding, a coupling-regularized dual-reconstruction bottleneck, and a graph attention encoder over a k -nearest-neighbor cell-cell graph. We assess this configuration within a decoupled benchmark that varies the algorithmic core, encoder backbone, graph construction, dataset cohort, and evaluation suite as independent axes. The cohort, drawn from the Gene Expression Omnibus (GEO) and the European Nucleotide Archive (ENA), balances scRNA-seq and scATAC-seq equally and spans hematopoiesis, neuronal differentiation, immune populations, organ atlases, tumor microenvironments, and developmental time courses. Across the cohort, scCCVGBen improves average silhouette width by + 0.288 and intrinsic-overall geometry by + 0.233 over a stochastic variational encoder (VAE) on paired scRNA-seq; gains over scVI reach + 0.341 and + 0.331 , and on scATAC-seq, the gain over PeakVI on intrinsic geometry reaches + 0.346 . Robustness analyses across 14 graph encoders and 5 graph-construction strategies show where alternative architectures remain competitive. Three paired hematopoietic case studies: sleep-disrupted bone marrow alongside a gastric tumor atlas, cord blood megakaryopoiesis alongside aged hematopoietic stem cells, and radiation-injury hematopoiesis alongside the COVID-19 bronchoalveolar landscape, recover coherent latent-gene programs spanning hematopoietic, epithelial-stromal, megakaryocytic, and antiviral-macrophage axes. The benchmark cohort, per-method scores, and per-dataset metadata are released through three companion sites: a Hugo atlas, a Next.js interactive cohort browser, and a cross-tool discovery surface, so the cohort can be inspected without cloning the source repository. The result is a stable, interpretable embedding that carries cleanly from benchmarking to biological discovery.

Esophageal sarcoma is an extremely rare tumor, and a recommended treatment strategy remains unestablished. The present report describes, to the best of our knowledge, the first reported case of unresectable esophageal sarcoma treated with chemoradiotherapy (CRT) followed by salvage robot-assisted minimally invasive esophagectomy (RAMIE). An 82-year-old man presented with dysphagia for solid foods. An esophagogastroduodenoscopy revealed an elevated tumor in the middle thoracic esophagus at a distance of 30-35 cm from the incisors, with preserved endoscopic passage and no additional lesions in the stomach or duodenum. A biopsy demonstrated sarcoma. Enhanced computed tomography showed a middle thoracic esophageal mass, with bulky mediastinal lymph nodes (nos. 101R and 106recR) invading the trachea. No distant metastases were detected, and tumor marker levels remained within normal limits. The patient was diagnosed with esophageal sarcoma with mediastinal lymph node metastases. As the metastatic nodes demonstrated airway invasion, definitive CRT (dCRT) was selected. The regimen consisted of radiotherapy (50.4 Gy in 28 fractions) and fluorouracil plus cisplatin. Following dCRT, the tumor and lymph nodes decreased in size, and a partial response was achieved, making the tumor resectable. Salvage RAMIE with two-field lymphadenectomy, including cervical lymph node dissection of stations 101R and 101L and upper mediastinal dissection, including station 106recR, was subsequently performed, followed by gastric tube reconstruction via the posterior mediastinal route. Pathological examination of the resected specimen revealed no residual tumor. Although a therapeutic effect was observed, a limitation remains in that a definitive diagnosis could not be fully established. A total of 14 months have passed since the initiation of treatment, with no evidence of recurrence. In conclusion, this patient with unresectable locally advanced esophageal sarcoma achieved a complete pathological response after multidisciplinary treatment, with no recurrence observed during the short-term follow-up period.

Neoadjuvant chemotherapy (NAC) represents a cornerstone in the management of locally advanced gastric cancer (GC); however, variability in therapeutic effect underscores the need for additional approaches to support post-operative risk stratification. The present study investigated circulating microRNA (miRNA)-30a as a potential post-treatment, response-associated indicator of therapeutic outcome in patients with GC undergoing NAC. Circulating miRNA-30a expression was measured in serum samples using quantitative real-time polymerase chain reaction (RT-qPCR). NAC-treated patients were stratified into responders (TRG 0-2) and non-responders (TRG 3-5) according to Mandards criteria, while chemotherapy-naive (CT-naive) patients were included as a control group. Circulating miRNA-30a levels were higher in responders compared to non-responders. Elevated miRNA-30a expression was associated with reduced pathological tumor burden, including lower T stage and absence of nodal involvement. ROC analysis demonstrated strong discriminatory performance for distinguishing treatment response. In both univariate and multivariable logistic regression analyses, increased miRNA-30a expression remained independently associated with treatment response. Furthermore, higher miRNA-30a levels were associated with improved overall survival. In conclusion, circulating miRNA-30a is associated with favorable therapeutic outcome in GC and may complement conventional assessment strategies in the post-treatment setting as a response-associated indicator. Further validation in larger, prospective cohorts is needed.

Gastric cancer (GC) progression is driven by an immunosuppressive tumor microenvironment (TME). Kynureninase (KYNU) is upregulated in GC and linked to poor prognosis, while platelet factor 4 (PF4)-induced nonclassical macrophages promote immune evasion. This study investigates whether KYNU regulates macrophage polarization via PF4 in GC. KYNU expression was modulated in GC cells to assess PF4 regulation and nonclassical macrophage polarization. Functional consequences were evaluated by proliferation, migration, invasion, and phagocytosis assays. Mechanistic studies included transcriptomics, PI3K/Akt manipulation, and rescue experiments. In vivo validation used a syngeneic mouse model, and clinical relevance was confirmed by multimarker tissue analysis. High KYNU expression in GC cells specifically promoted macrophage polarization toward a nonclassical phenotype characterized by S100A8 and MMP7 expression. These non-classical polarized macrophages subsequently enhanced GC cell proliferation, migration, and invasion while suppressing phagocytic activity. Mechanistically, KYNU upregulated PF4 expression with the involvement of the PI3K/Akt signaling pathway, which in turn drove nonclassical macrophage polarization. In vivo studies demonstrated that KYNU promoted tumor growth through this pathway, whereas PI3K/Akt inhibition suppressed both tumor progression and nonclassical macrophage infiltration. Clinical analysis further confirmed the coordinated upregulation of KYNU, p-Akt, PF4, and S100A8 in human GC tissues. KYNU acts as a signaling transducer in GC, involving PI3K/Akt to upregulate PF4, driving nonclassical macrophage polarization and tumor progression. This mechanism represents a novel pathogenic driver and a promising therapeutic target for reprogramming the immunosuppressive TME.

Epidemiological studies have revealed an inverse association between Alzheimer's disease and cancer. Here, we discuss the mechanisms involved in the relationship between Alzheimer's disease and gastrointestinal cancers, particularly pancreatic and gastric-colorectal cancers. The gut‒brain axis and pancreas‒brain axis connect the central nervous system with peripheral organs and form immune‒metabolic networks. We focus on bidirectional tumor-brain communication, involving cell-death pathways, apoptosis, metabolic dysregulation, microbiota, metabolic dysregulation, neuroinflammation, immune system and sensory-sympathetic circuits, and neural remodeling. Furthermore, we discuss potential integrated, multitarget therapeutic strategies, including metabolic regulation, microbiome interventions, and immune modulation. Prospective longitudinal cohorts incorporating prediagnostic exposures and molecular pathology are needed to establish temporality.

Gastrointestinal cancers remain among the leading causes of cancer-related mortality worldwide. Beyond environmental and hereditary determinants, increasing evidence suggests that the gut microbiota may contribute to carcinogenesis through persistent infection, expression of virulence factors, and production of genotoxic metabolites. In this context, Helicobacter pylori has been firmly implicated in gastric carcinogenesis, while colibactin-producing Escherichia coli has emerged as a potential contributor to colorectal cancer development. The aim of this study was to explore the presence of colibactin-associated E. coli and virulence factor-harboring H. pylori strains in gastrointestinal cancer patients from a Turkish cohort. Tumor samples were collected from 19 patients with colorectal cancer and 4 patients with gastric cancer. In colorectal cancer samples, the presence of colibactin was assessed by screening for key genes (clbA, clbB, clbN, and clbQ). In gastric cancer samples, major H. pylori virulence determinants, including ureA, cagA, and vacA, were evaluated. Colibactin-associated genes were detected in approximately 21% of colorectal cancer patients (4/19), whereas 75% of gastric cancer cases (3/4) were positive for H. pylori virulence factors. Whole-genome sequencing (WGS) of two colibactin-positive isolates identified them as Escherichia coli Nissle and Citrobacter braakii. Given the limited sample size and exploratory design, these results are descriptive and intended to provide preliminary insight rather than establish causality. In conclusion, this study provides early evidence supporting the potential presence of genotoxin-associated bacteria and virulent H. pylori strains in gastrointestinal cancer patients in Türkiye. These findings underscore the need for larger, well-powered, and multi-omics-integrated studies to further elucidate the role of host-microbe interactions in gastrointestinal carcinogenesis.

Peritoneal metastasis of gastric cancer (PMGC) is associated with a poor prognosis, with approximately one-third of patients presenting with peritoneal metastasis at diagnosis. Current systemic therapies have limited efficacy, underscoring the need for precise therapeutic targets in PMGC. We employed single-cell RNA sequencing (scRNA-seq) to characterize the cellular composition of the PMGC microenvironment, reconstruct epithelial cell developmental trajectories, and analyze intercellular communication networks. Spatial transcriptomics and multiplex immunohistochemistry were integrated to validate targets, and in vivo mouse models were used to assess therapeutic efficacy. Single-cell analysis identified a peritoneal metastasis (PM) signature associated with cancer cell differentiation origin and poor outcomes. We classified cancer cells as PM-high or PM-low based on this signature, with the PM-high group enriched in multiple oncogenic pathways and the PM-low group overexpressing CLDN18. Intercellular communication analyses showed epithelial cells and diverse subsets interact with regulatory T, natural killer, and proliferative T cells via PVR-TIGIT and NECTIN2-TIGIT. In vivo studies indicated that dual targeting of TIGIT and Claudin 18.2 (CLDN18.2) inhibited PMGC progression and ascites formation. These findings indicate that CLDN18.2 and TIGIT are potential therapeutic targets, whose combined inhibition suppresses PMGC progression and ascites formation, providing valuable insights for PMGC treatment.