Pan-cancer characterization of POSTN and its clinical and microenvironmental associations in ER

Periostin (POSTN) is implicated in the progression of multiple malignancies; however, its pan-cancer landscape and clinical relevance in estrogen receptor (ER)-positive breast cancer remain insufficiently characterized. This study aimed to clarify the clinical significance of POSTN via pan-cancer analyses and to further explore its association with ER+ breast cancer. Public resources including Tumor Immune Estimation Resource 2.0 (TIMER2.0), The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Gene Expression Omnibus (GEO) were integrated to investigate POSTN expression patterns and their associations with prognosis, genetic/epigenetic alterations, tumor microenvironment (TME) features, and drug-response indicators. In the ER+ breast cancer cohort (defined by clinical ER annotation; PAM50 was used for molecular subtype stratification), differential expression, immune infiltration, drug–gene association analyses, and in vitro functional assays were performed. POSTN showed diagnostic and prognostic relevance in multiple cancer types and was associated with clinicopathological stage and molecular subtypes. POSTN expression correlated with TME-related features, particularly macrophages and cancer-associated fibroblasts (CAFs), and with immune-regulatory gene signatures. Drug–gene association analyses suggested that POSTN expression was related to differential predicted sensitivity/resistance to several small-molecule agents. Silencing POSTN reduced the migratory and invasive capacity of ER+ breast cancer cells. POSTN may serve as a candidate diagnostic and prognostic biomarker across cancers. In ER+ breast cancer, its expression is closely linked to stromal and immune features, supporting POSTN as a candidate microenvironment-associated biomarker with potential translational relevance.