EMBO Mol Med. 2026 Mar 30. doi: 10.1038/s44321-026-00410-y. Online ahead of print.

ABSTRACT

Lung cancer is the leading cause of cancer-related mortality worldwide, with lung squamous cell carcinoma (LUSC) comprising 20-30% of cases. Immunochemotherapy (IC) is the standard first-line treatment for advanced LUSC, yet reliable predictors of therapeutic response remain unavailable. Using single-cell multi-omics profiling of paired pre- and post-treatment tumor and blood samples, we observed that patients responding to IC exhibited significantly higher baseline levels of peripheral blood monocytes, tumor-infiltrating classical monocytes, and APOBEC3A+ monocytes across both compartments compared with non-responders. These associations were independently validated in additional cohorts using routine complete blood count testing and multiplex immunofluorescence analysis of native tumor tissues. Our findings reveal monocyte-related parameters as clinically accessible indicators that link systemic immunity with the tumor microenvironment and hold promise for predicting IC responsiveness in patients with LUSC.

PMID:41912871 | DOI:10.1038/s44321-026-00410-y

EMBO Mol Med. 2026 Mar 30. doi: 10.1038/s44321-026-00410-y. Online ahead of print.

ABSTRACT

Lung cancer is the leading cause of cancer-related mortality worldwide, with lung squamous cell carcinoma (LUSC) comprising 20-30% of cases. Immunochemotherapy (IC) is the standard first-line treatment for advanced LUSC, yet reliable predictors of therapeutic response remain unavailable. Using single-cell multi-omics profiling of paired pre- and post-treatment tumor and blood samples, we observed that patients responding to IC exhibited significantly higher baseline levels of peripheral blood monocytes, tumor-infiltrating classical monocytes, and APOBEC3A+ monocytes across both compartments compared with non-responders. These associations were independently validated in additional cohorts using routine complete blood count testing and multiplex immunofluorescence analysis of native tumor tissues. Our findings reveal monocyte-related parameters as clinically accessible indicators that link systemic immunity with the tumor microenvironment and hold promise for predicting IC responsiveness in patients with LUSC.

PMID:41912871 | DOI:10.1038/s44321-026-00410-y

J Int Med Res. 2026 Mar;54(3):3000605261430163. doi: 10.1177/03000605261430163. Epub 2026 Mar 16.

ABSTRACT

ObjectiveTo explore the potential involvement of PANoptosis-related genes in gastric cancer susceptibility through multiomics analyses.MethodsSummary-data-based Mendelian randomization was performed by integrating blood-derived methylation, gene expression, and protein quantitative trait loci data with genome-wide association study results. The findings were further evaluated in The Cancer Genome Atlas cohort, followed by protein-protein interaction analysis, drug prediction, and molecular docking.ResultsSummary-data-based Mendelian randomization and colocalization analyses identified several traits suggestively associated with gastric cancer risk. Genetically predicted higher expression of apoptosis and caspase activation inhibitor (AVEN) and hepatocyte growth factor (HGF) as well as higher HGF protein levels were associated with increased risk, whereas higher levels of protein phosphatase 2 regulatory subunit B beta (PPP2R2B) appeared to be protective. Multiomics integration suggested epigenetic regulation of HGF and PPP2R2B. The Cancer Genome Atlas analysis corroborated the dysregulation of these candidates, with high AVEN expression associated with poorer survival. Protein-protein interaction and drug prediction analyses highlighted functional networks and potential therapeutics, supported by molecular docking demonstrating strong HGF-binding affinities. However, these associations did not reach statistical significance in the independent validation cohort, possibly due to limited statistical power.ConclusionsThis study identified AVEN, HGF, and PPP2R2B as potential candidate genes for gastric cancer. These findings require further validation in larger cohorts.

PMID:41840829 | DOI:10.1177/03000605261430163