Angiogenesis gene signatures in patient-derived tumor spheroids for genetic and tumor angiogenesis profiling†

Background: gastric cancers are highly vascular tumors, with elevated pro-angiogenic factors correlating with a poor prognosis. Despite advancements in precision medicine, there remains a critical need for platforms capable of identifying patient-specific therapeutic vulnerabilities. In this study, we present a 3D-printed patient-specific tumor angiogenesis chip that integrates genetic data to evaluate the molecular and functional characteristics of tumor angiogenesis in tumor spheroids derived from patients with gastric cancer. Results: whole-transcriptome analysis classified tumor spheroids into high- and low-angiogenesis-related gene signatures groups. Tumors with high angiogenesis-related gene signatures exhibited significantly enhanced blood vessel formation and tumor growth on the 3D tumor angiogenesis chips compared to those with low gene signatures [vessel density: 1.091 vs. 0.7538; vessel length: 1.070 vs. 0.8344; and angiogenic sprouting number: 1.184 vs. 0.6541]. The platform also enabled quantitative drug response assessments, providing a robust framework for evaluating treatment efficacy. Conclusion: these 3D-printed tumor angiogenesis chips, leveraging genomic profiling and patient-specific tumor characteristics, offer a powerful tool for advancing personalized medicine in gastric cancer.