Integrating single-cell and bulk transcriptomes, we delineate a single-cell–anchored, glutamine-coupled program in OS, preferentially expressed by osteoblastic tumor cells, and distill it into a five-gene signature (GPX7, COL11A2, CPE, MSMO1, SGMS2) with moderate yet reproducible prognostic performance across independent cohorts. Here, SGMS2 is linked to neoplasm.