Elevated SOX9 Expression Is Associated With Extracellular Matrix Remodelling and Aggressive Clinicopathological...

Extramammary Paget's disease (EMPD) is a rare cutaneous adenocarcinoma that remains clinically challenging in advanced or metastatic stages, yet the molecular mechanisms underlying tumour invasion and metastasis remain poorly understood. SOX9 has emerged as a critical factor in tumour invasion and metastasis across several cancers, but its role in EMPD has not been systematically characterized. In this study, we established a cohort of 93 patients with genital EMPD and performed integrated transcriptomic and proteomic profiling to assess the expression and clinical significance of SOX9. We found that elevated SOX9 transcript levels were significantly associated with tumour invasion, whereas increased SOX9 protein abundance correlated with metastatic progression. To explore the potential functional relevance, we established a SOX9-overexpressing cellular model as a preliminary approach and performed combined transcriptomic and extracellular matrix (ECM) proteomic analyses. Functionally, SOX9 overexpression enhanced cellular migratory capacity in vitro. Both transcriptomic and proteomic profiles converged on the regulation of extracellular matrix organisation, with SOX9 overexpression associated with increased expression of ECM-related genes including MMP1, MMP10 and MMP12, as well as increased abundance of ECM proteins such as FMOD and COL1A2. Collectively, these findings suggest that SOX9 may serve as a promising indicator of aggressive clinicopathological features in EMPD and provide preliminary evidence linking its overexpression to ECM-related molecular changes and enhanced cellular migratory capacity in vitro. Further validation in independent cohorts and functional models is warranted.