NPJ Precis Oncol. 2026 Mar 31. doi: 10.1038/s41698-026-01394-1. Online ahead of print.

ABSTRACT

VDAC2's known role in cancer and immune regulation via enhancing the CD8⁺ T cell-mediated killing, and it is worth systematically digging out the role of VDAC2 in pan-cancer based on this research. Bulk RNA sequencing, single-cell RNA sequencing, and spatial transcriptomic analyses were utilized to explore the role of VDAC2 from multiple perspectives in pan-cancers. RT-PCR, cell co-culture, CCK-8 assay, Transwell invasion assays, and ELISA were performed to validate the expression level and biological function. VDAC2 was upregulated in the majority of pan-cancers, and functional enrichment analyses displayed that VDAC2 may take part in the biological progress of energy metabolism, mitochondrial damage and cell proliferation. The landscape of VDAC2 expression and immune infiltration was constructed, and the VDAC2-BAK1-IFNγ pathway was identified in digestive cancer. VDAC2 had the potential to serve as a novel prognostic, screening cancer indicator and immune therapeutic target sensitive to various drugs. Overexpression of VDAC2 significantly promoted gastric cancer cell proliferation, invasion and immune invasion, as validated in vitro experiments. In short, our pan-cancer analysis constructed a comprehensive landscape of VDAC2's oncogenic role, establishing VDAC2 + -BAK1-IFNγ as an important pathway in tumor progression and immune evasion. VDAC2 emerges not only as a valuable prognostic biomarker but also as a promising novel therapeutic target.

PMID:41917254 | DOI:10.1038/s41698-026-01394-1

Food Funct. 2026 Mar 31. doi: 10.1039/d5fo04958j. Online ahead of print.

ABSTRACT

The probiotic yeast Saccharomyces boulardii is renowned for its clinical efficacy, which is intrinsically linked to its exceptional ability to survive the harsh gastrointestinal (GI) environment. However, a comprehensive understanding of the molecular mechanisms and regulatory pathways underlying the stress tolerance of S. boulardii remains limited. This study employed an integrated transcriptomic and proteomic approach to systematically map the dynamic responses of S. boulardii to simulated GI transit. Our analysis revealed that the intestinal phase posed a significantly greater challenge than the gastric phase, triggering extensive molecular reprogramming. A core adaptive strategy was the marked upregulation of the central carbon metabolism, particularly glycolysis, as evidenced by the concerted overexpression of key enzymes at both transcriptional and translational levels, indicating a heightened demand for energy to fuel stress defence mechanisms. Furthermore, significant enrichment was observed in the pathways related to nitrogen and fatty acid metabolism. Integration of the multi-omics datasets highlighted the complexity of the regulatory response, with frequent discordance between mRNA and protein abundance underscoring the importance of post-transcriptional regulation. This study provides a detailed molecular profile of the stress tolerance network in S. boulardii, elucidating the strategic metabolic rewiring and multi-layered regulation that underpin its probiotic resilience. The findings offer valuable insights and a foundational resource for the future development of enhanced probiotic therapies.

PMID:41914832 | DOI:10.1039/d5fo04958j

Aging Dis. 2026 Mar 19. doi: 10.14336/AD.2025.1571. Online ahead of print.

ABSTRACT

Gastric cancer (GC) remains a leading cause of cancer-related morbidity and mortality worldwide, with poor prognosis for advanced-stage patients. Therefore, in-depth exploration of the mechanisms underlying GC initiation and progression, as well as the development of novel therapeutic strategies, is of crucial importance. Cellular senescence is a stable cell cycle arrest program that plays a dual role in GC. It exerts tumor-suppressive effects via growth arrest but also promotes tumor progression and immune evasion by remodeling the tumor microenvironment (TME) through senescence-associated secretory phenotype (SASP). This review comprehensively elucidates the molecular mechanisms of cellular senescence in GC and the core regulatory networks involving gene regulation, epigenetic modifications, metabolic reprogramming, and cell cycle arrest. Additionally, the review highlights how senescent cells foster an immunosuppressive microenvironment via SASP, forming a self-reinforcing feed-forward loop. Regarding therapeutic strategies, we summarize potential approaches targeting cellular senescence, including senescence induction, senescent cell clearance, SASP modulation, and multi-target synergistic therapy by integrating epigenetic regulation, metabolic intervention, and immune microenvironment modulation. Despite progress, numerous challenges remain. Future studies should leverage multi-omics technologies, novel models' development, and large-scale clinical trials to advance the clinical translation of GC cellular senescence research, providing new insights for improving prognosis.

PMID:41910653 | DOI:10.14336/AD.2025.1571

Cells. 2026 Mar 17;15(6):535. doi: 10.3390/cells15060535.

ABSTRACT

Gastric cancer (GC) remains a major global health burden, with its unfavorable prognosis primarily driven by extensive tumor heterogeneity. Traditional bulk omics, while informative, are inherently limited by the averaging effect of diverse cell populations and fail to capture the critical spatial molecular disparities within the tumor and its microenvironment (TME). Single-cell omics can capture cellular heterogeneity but lack spatial context. Therefore, there is an urgent clinical need for spatial multi-omics to provide a high-definition dissection of GC heterogeneity and to optimize therapeutic efficacy. This review first outlines briefly the evolution of spatial technologies, including transcriptomics, proteomics, metabolomics, genomics and epigenomics, and their transformative applications in GC research. We further explore how these platforms refine molecular classification beyond traditional models, identify next-generation biomarkers, and decode the intricate cellular interactions governing immune evasion and metastasis. Next, we highlight the pivotal role of spatial profiling in unravelling the multidimensional mechanisms of resistance to chemotherapy, targeted therapy and immunotherapy. Finally, we address current technical bottlenecks and discuss prospects for clinical translation.

PMID:41892326 | PMC:PMC13025482 | DOI:10.3390/cells15060535

Biochem Biophys Rep. 2026 Mar 16;46:102537. doi: 10.1016/j.bbrep.2026.102537. eCollection 2026 Jun.

ABSTRACT

BACKGROUND: Although studies have shown that the androgen receptor (AR) is associated with tumor progression and malignant regulation, its role in the tumor immune microenvironment and predictive value for prognosis and immunotherapy response in various cancer types have not been systematically analyzed.

METHODS: In this paper, multi-omics techniques was used to analyze AR comprehensively.

RESULTS: A comprehensive pan-cancer analysis revealed that the AR was expressed in a variety of tumors, especially as a risk factor for poor prognosis in gastric cancer. In addition, gene set enrichment analysis showed that the AR promotes cell proliferation and tumor cell invasion and regulates anti-tumor response. Immune score, immune cell infiltration, and anticancer immune cycle analysis showed that high AR levels were correlated with low infiltration of CD4⁺ T cells and NKT cells, high infiltration of Th2 cells and MDSCs, negatively correlated with antigen-presenting molecules, and positively correlated with various immune-negative regulatory molecules. Single-cell sequencing highlighted the heterogeneous expression of ARs in different cell types, particularly in epithelial cells, where high AR levels were associated with the enhanced activity of tumor-promoting pathways.

CONCLUSIONS: In conclusion, this study highlights the potential of the AR as a novel biomarker for gastric cancer prognosis and immunotherapy efficacy, expanding its applicability in the development of new antitumor drugs.

PMID:41890218 | PMC:PMC13014673 | DOI:10.1016/j.bbrep.2026.102537

Cell Oncol (Dordr). 2026 Mar 23;49(2):60. doi: 10.1007/s13402-026-01194-6.

ABSTRACT

Glycolytic reprogramming is closely associated with the occurrence and progression of gastric cancer. Specifically, the energy derived from glucose metabolism and the cellular proteins by its intermediate products influence gastric cancer development. However, as an important branch of glucose metabolism, sialic acid metabolism and its mediated sialylation modifications remain insufficiently studied in gastric cancer, and their specific relationship with malignant tumor progression requires further exploration. This study employed a multi‑omics approach, integrating metabolomics, single‑cell RNA sequencing, and bulk RNA sequencing analyses, to investigate the metabolic landscape of gastric cancer and its associated alterations. The results indicated that sialic acid is a characteristic metabolite in malignant gastric cancer tissues. It modulates biological functions such as immune response, proliferative activity, and metabolic remodeling within gastric cancer tissues by influencing sialylation modifications. Furthermore, we identified the drug WZ35, which can inhibit the malignant proliferation of gastric cancer by targeting both sialic acid metabolism and sialylated protein modifications. We put forward a conjecture that the metabolism and modification of sialic acid promote the malignant development of gastric cancer, and we discovered that the drug WZ35 has an inhibitory effect on the sialic acid metabolism of gastric cancer.

GRAPHICAL ABSTRACT:

PMID:41870836 | PMC:PMC13009457 | DOI:10.1007/s13402-026-01194-6