Fig. 1: Low body mass index (BMI) is associated with increased brain metastasis in lung cancer.

A Percentage of brain metastatic incidence across lung, breast, melanoma, and renal cancers (n = 7628), stratified by BMI status. Patients with BMI < 25 were categorized as low BMI (BMI^low) and those with BMI > 25 as high BMI (BMI^high) (two-sided Fischer’s exact test). B Percentage of metastatic incidence in the brain, bone and liver within a lung cancer cohort (n = 2366) comprising both low and high BMI patients (two-sided Fischer exact test). C Left: Representative hematoxylin and eosin (H&E) and Ki-67 immunohistochemistry images of brain metastatic tumor lesions from lung cancer patients, stratified by BMI [Scale bar: 100μm (H&E), 50μm (Ki-67); insert: 2 x Zoom]. Right: Dot plot showing quantification of Ki-67+ cells in brain metastatic tumor lesions from low and high BMI patients using H-score (n = 7 each, unpaired two-tailed t-test). D Left: Schematic of in vivo metastasis assay. Immune-competent C57BL/6 (female, 5–6 week) mice were fed with a standard or 50% calorie-restricted diet (CRD; 12-hr/dark phase) for 15 days to establish low BMI mice, followed by intracardiac injection (i.c.) of murine lung cancer cell line, CMT167 cells (5 × 10⁴). Right: Average body weight curve during the experiment (two-way ANOVA with Tukey’s test). E Top left: Representative in vivo (top) and ex vivo (bottom) BLI images of brain metastasis at endpoint. Middle/Right: In vivo and ex vivo BLI quantification of brain metastasis in normal (n = 7) and low BMI (n = 8) mice at endpoint (two-way ANOVA with Tukey’s test (in vivo); unpaired two-tailed t-test (ex vivo). Bottom: Representative H&E images of brain metastatic tumor lesions from normal and low BMI mice (Scale bar: 50 μm). F Kaplan–Meier analysis of brain metastasis-free survival in normal (n = 7) and low BMI (n = 8) mice [log-rank (Mantel–Cox test)]. G Representative ex vivo BLI images and quantification of lung, liver and bone metastasis in normal and low BMI mice (n = 6/group) at endpoint (unpaired two-tailed t-test). All data are mean ± S.E.M. Source data are provided as a Source Data file.