Front Immunol. 2026 Feb 13;17:1743187. doi: 10.3389/fimmu.2026.1743187. eCollection 2026.

ABSTRACT

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC), an aggressive cancer with poor prognosis, poses major challenges owing to late diagnosis and limited response to current therapies. However, the identification of candidate drugs through multi-omics analyses and therapeutic peptides targeting key molecular pathways may provide improved outcomes. Although lactate metabolism is a critical factor in tumor progression, affecting cell proliferation, metastasis, and immune evasion, its role in PDAC-particularly within the tumor microenvironment, remains underexplored.

OBJECTIVES: This study investigated lactate metabolism in PDAC using high-throughput transcriptomic sequencing and single-cell transcriptomic analysis.

METHODS: Lactate metabolism-related gene expression was analyzed in tumor cells and their microenvironment, and correlations with patient prognosis were determined. Additionally, a machine learning-based prognostic model was established to identify lactate metabolism biomarkers for early diagnosis and personalized therapy.

RESULTS: Lactate metabolism significantly impacted the survival of patients with PDAC (n = 92; log-rank test, p < 0.05). Single-cell RNA and spatial transcriptomics analyses of 50, 795 cells from 8 PDAC samples revealed that 521 malignant cells exhibited hyperactive lactate metabolism (AUCell score comparison, p < 0.001). A prognostic model constructed from lactate metabolism-related genes using ensemble machine learning (StepCox + Enet, α = 0.5) effectively stratified patients into high- and low-risk groups across multiple cohorts (ICGC: n = 92; GSE28735: n = 45; GSE62452: n = 69; GSE183795: n = 139; all log-rank p < 0.05). Key prognostic genes identified included lysozyme (LYZ) and polymeric immunoglobulin receptor, which were significantly associated with patient survival (univariate Cox regression, p < 0.05). These genes may serve as clinical biomarkers of PDAC.

CONCLUSIONS: This study provides insights into PDAC metabolic features and highlights lactate metabolism as a potential therapeutic target. The identified biomarkers could facilitate early diagnosis and improve treatment strategies, ultimately enhancing patient outcomes.

PMID:41766855 | PMC:PMC12946077 | DOI:10.3389/fimmu.2026.1743187

Aging Dis. 2025 Dec 15. doi: 10.14336/AD.2025.1444. Online ahead of print.

ABSTRACT

Chronic gastritis (CG) is a highly prevalent, age-associated inflammatory disorder of gastric mucosa and a key precursor of gastric cancer in older adults. Beyond Helicobacter pylori infection and environmental insults, accumulating evidence indicates that chronic, low-grade inflammation coupled with aging biology, "gastric inflammaging", plays a central role in driving mucosal degeneration, atrophy, and malignant transformation. Here, we synthesize current mechanistic and multi-omics evidence to conceptualize CG as a tractable model of organ-specific inflammaging. We first summarize how hallmarks of aging-including cellular senescence and the senescence-associated secretory phenotype (SASP), mitochondrial dysfunction, impaired autophagy, immune exhaustion, and microbiome dysbiosis-converge to create a self-perpetuating inflammatory microenvironment in the stomach. We then review emerging single-cell and spatial multi-omics studies that delineate senescence-inflammation niches and reveal how these molecular neighborhoods relate to disease stage and cancer risk. Finally, we discuss therapeutic implications, highlighting geroscience-guided interventions such as senolytics/senomorphics, inflammasome and cGAS-STING pathway modulators, microbiota- and metabolite-targeted strategies, lifestyle interventions, and natural products, and propose a precision framework linking inflammaging biomarkers to patient stratification and clinical endpoints. Reframing CG as a gastric inflammaging model may provide a prototype for organ-specific healthy aging strategies and near-term gerotherapeutic trials aimed at extending healthspan.

PMID:41400573 | DOI:10.14336/AD.2025.1444