Spatial analysis using immunofluorescent staining indicated a close spatial relationship between IGFBP2+ fibroblasts and SPP1+ macrophages in lung cancer tissues, with a significant correlation observed between SPP1 and IGFBP2 expressions in LUSC (Fig. 1G), suggesting their involvement in the transition between adenocarcinoma and squamous cell carcinoma (Fig. S3E). Here, IGFBP2 is linked to squamous cell carcinoma.