Deciphering INHBA As An Invasive Factor In Ameloblastoma Spatial Heterogeneity

As a benign odontogenic tumor, the mechanisms underlying the invasive biological behavior of ameloblastoma (AB) remain unclear, while this study aims to identify the key factor(s) driving AB invasion and elucidate its/their role in the local spread. Through the multi-omics integration optimization algorithm SaCET (Spatial Cellular Estimator for Tumors), spatial transcriptomics data, copy number variation (CNV), and histopathological image information were integrated to achieve high-precision identification of the progression front line of AB. Moreover, markers representing the spatial heterogeneity of the tumor's internal tissue were extracted and overlapped with invasion-related differentially expressed genes (DEGs) revealed by bioinformatic methods to identify the key invasion factor in AB. Validation based on AB patient-derived organoids (PDO) was then performed. The SaCET algorithm identified 1826 over-expressed markers in the leading edge of AB. It was found that the TGF-β signaling pathway component INHBA was significantly up-regulated in the leading edge and enriched in tumor cells. Co-expression analysis and PDO validation revealed significant correlations between INHBA and invasive EMT-related molecules, while functional analysis suggested that INHBA promotes local invasion by regulating tumor metastasis related biological functions. INHBA is notably up-regulated in the leading edge of AB and identified as a key marker for AB invasion by a spatial heterogeneity-driven strategy. INHBA regulates cell proliferation, differentiation, apoptosis, and the tumor microenvironment through the TGF-β signaling pathway, which exerts a promoting effect during the local spread of AB.