Elevated POSTN expression predicts poor prognosis and is associated with radioresistance in cervical cancer patients treated with radical radiotherapy

Cervical cancer (CC) is a significant global health issue and remains one of the leading causes of cancer-related mortality in women. Radiotherapy is a crucial treatment modality for CC; however, tumor heterogeneity and resistance to radiotherapy often result in suboptimal outcomes for some patients, including recurrence and metastasis. Periostin (POSTN), a matricellular protein within the tumor microenvironment, has been implicated in the promotion of tumor progression and treatment resistance, particularly through mechanisms such as epithelial-mesenchymal transition (EMT). Despite this, the role of POSTN in radiotherapy resistance in CC patients remains underexplored. Therefore, in this study, we investigated the prognostic significance of POSTN expression in CC patients undergoing radical radiotherapy and explored potential mechanisms underlying radiotherapy resistance. We analyzed data from 92 CC patients in The Cancer Genome Atlas (TCGA) and 153 patients from our institution, assessing POSTN expression levels through mRNA analysis and immunohistochemistry (IHC). Our findings revealed that high POSTN expression was significantly associated with advanced tumor stages, poorer radiotherapy outcomes, and worse overall survival (OS). Additionally, multivariate Cox regression analysis identified POSTN as an independent prognostic factor for CC patients undergoing radical radiotherapy. A prognostic nomogram integrating POSTN expression and clinicopathological features demonstrated superior predictive accuracy for OS. Drug sensitivity analysis suggested that high POSTN expression may be linked to resistance to multiple chemotherapeutic agents. Furthermore, weighted correlation network analysis (WGCNA) and gene set enrichment analysis (GSEA) identified EMT as a top enriched pathway in patients with high POSTN expression, suggesting it may play a critical role in radiotherapy resistance. Subsequently, in vitro experiments confirmed that POSTN knockdown significantly inhibited HeLa cell proliferation, invasion, and enhanced radiosensitivity, while promoting apoptosis. These findings indicate that high POSTN expression is a risk factor for poor prognosis in CC patients undergoing radical radiotherapy, and targeting POSTN may improve radiotherapy efficacy by reducing tumor proliferation and resistance.