iScience. 2026 Mar 3;29(4):115203. doi: 10.1016/j.isci.2026.115203. eCollection 2026 Apr 17.

ABSTRACT

Mass spectrometry imaging (MSI)-based spatial metabolomics exhibits extensive missing values; yet, practical guidance on how imputation choices affect both imputation accuracy and downstream spatial analyses remains limited. In this study, we evaluated eight imputation methods, including both existing approaches and a graph convolutional network (GCN)-based method specifically designed for spatial metabolomics data, to identify suitable approaches for spatial metabolomics. To enable comprehensive assessment, we developed an evaluation framework focusing on two objective criteria: (a) imputation accuracy and (b) preservation of spatial cluster structure. We assembled six benchmark datasets spanning mouse brain and liver, human kidney and stomach, and plant seed sections, and conducted controlled dropout simulations of missing values. Across both evaluation dimensions, including imputation accuracy and preservation of spatial cluster structure, RF ranked first overall, and GCN ranked second in both dimensions. Overall, this systematic, dual-perspective benchmark study provides guidance for selecting imputation strategies in spatial metabolomics research.

PMID:41869568 | PMC:PMC12999350 | DOI:10.1016/j.isci.2026.115203

Clin Cancer Res. 2026 Mar 18. doi: 10.1158/1078-0432.CCR-25-4153. Online ahead of print.

ABSTRACT

PURPOSE: Intestinal low-dose irradiation (ILDR) may enhance immunotherapy efficacy by modulating the gut microbiota and metabolism; however, its role in metastatic non-small cell lung cancer (mNSCLC), particularly in the first-line setting, remains unclear.

EXPERIMENTAL DESIGN: This multicenter retrospective and prospective study included mNSCLC patients receiving first- and second-line programmed cell death protein 1 (PD-1) inhibitors along with abdominopelvic radiotherapy between 2018 and 2025. Patients were stratified by the mean intestinal radiation dose into <1 Gy, 1-3 Gy, and >3 Gy groups and treatment outcomes were compared. The blood and fecal samples were subjected to multi-omics profiling.

RESULTS: g>309 patients were included in the retrospective analysis. Optimal efficacy was observed with a small intestinal mean radiation dose (SIMRD) of 1-3 Gy, showing longer progression-free survival (PFS, 10.2 months) and overall survival (OS, 22.8 months) (P < 0.01), which was consistent across subgroups. Compared with 1-3 Gy, SIMRD >3 Gy (Hazard ratio [HR] = 4.87, P < 0.001) and <1 Gy (HR = 1.85, P < 0.001) independently predicted worse OS. Prospective results confirmed the best disease control rate (P = 0.041) and PFS (P = 0.046) with SIMRD of 1-3 Gy. Responders were enriched in Bacillota, Clostridia, and indole derivatives, particularly indole-3-carboxylic acid. Moreover, the 1-3 Gy group exhibited increased circulating macrophage inflammatory protein-3α and reduced circulating α4β7+ regulatory T cells.

CONCLUSIONS: ILDR influences the efficacy of PD-1 blockade in patients with mNSCLC, particularly when SIMRD is maintained within the 1-3 Gy range, likely through modulation of the gut microbiota-metabolite-immune axis.

PMID:41849236 | DOI:10.1158/1078-0432.CCR-25-4153