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Glioblastoma (GBM) heterogeneity limits the efficacy of EGFR‐targeted therapies. Here, we present a spatially stratified single‐cell atlas of IDH‐wildtype GBM to dissect the impact of EGFR amplification on tumor architecture. We demonstrate that EGFR amplification disrupts the spatial coupling between evolutionary state and anatomical location, resulting in premature acquisition of invasive phenotypes—a phenomenon we term “accelerated evolutionary velocity.” Unlike nonamplified tumors which maintain a strict “Core‐to‐Margin” developmental gradient, malignant cells in EGFR‐amplified tumors acquire invasive mesenchymal traits preemptively regardless of their spatial niche. This accelerated evolution parallels the Core behaving as a “genotoxic stress reservoir” characterized by elevated chromosomal instability (CIN) (p < 2.2 × 10−16). This genotoxic stress coincides with the emergence of a localized tumor–myeloid axis and an immune‐suppressive niche. Using the PriorityScore2 framework, we prioritized Periostin (POSTN) as a top‐tier clinically relevant candidate. In the high‐CIN environment of EGFR‐amplified GBM, in silico network perturbation suggested that POSTN may function as a candidate modulator of mitotic fidelity, potentially buffering against lethal genomic instability while sustaining rapid clonal evolution. Validated across multicenter cohorts, POSTN showed robust upregulation, strong diagnostic performance (AUC = 0.961), and significant prognostic relevance, emerging as a potential therapeutic vulnerability linking accelerated evolution with immune privilege in the GBM ecosystem.

Periostin is a matricellular protein induced by type 2 cytokines. It has been shown to play important roles in airway inflammation and tissue remodeling. Although periostin has been studied in asthma and chronic rhinosinusitis, its role in allergic rhinitis (AR) and nasal hyperresponsiveness (NHR) is unclear. This study aimed to determine whether periostin is involved in the development of NHR in AR. A murine AR model was established by sensitization and repeated intranasal challenges with Japanese cedar pollen (JCP). In this animal model of AR, an increase in nasal responsiveness to histamine was observed 24 h after the last JCP challenge, indicating the development of NHR. RT-qPCR analysis revealed that the JCP-induced NHR was accompanied by increased periostin gene expression. Immunohistochemical examinations demonstrated the expression of integrin subunits αV (Itgav), β3 (Itgb3) and β5 (Itgb5), which are known as receptors for periostin, in the nasal mucosa, especially in the mucosal epithelium. Notably, repeated intranasal administration of recombinant periostin to healthy I mice reproduced the NHR phenotype, as observed in AR model mice. These findings suggest that periostin upregulation in the nasal mucosa plays a causal role in the development of NHR, a key feature of AR.

Early diagnosis of chronic kidney disease (CKD) remains a major clinical challenge. Periostin (POST) and kidney injury molecule-1 (KIM-1) have been proposed as biomarkers of tubular injury and fibrosis. This study aimed to evaluate their utility as markers associated with CKD stage and their associations with renal function and proteinuria in children. Twenty-three children with CKD stages I–IV and 23 healthy controls were enrolled. Serum and urinary POST and KIM-1 were measured together with creatinine (CR), cystatin C (CysC), proteinuria, albuminuria, and urinary α1- and β2-microglobulin. Patients were classified as early stage (ES; CKD I–II) or late stage (LS; CKD III–IV). Serum and urinary POST and KIM-1, uPOST/CR, uKIM-1/CR, fractional excretion indices (FePOST, FeKIM-1), and UPCR were higher in CKD patients than in controls. Absolute biomarker concentrations did not differ between ES and LS and were not associated with eGFR, UPCR, UACR, or tubular protein excretion. In contrast, uPOST/CR, uKIM-1/CR, FePOST, and FeKIM-1 increased with CKD stage, were higher in LS than ES, correlated positively with CysC, and inversely with eGFR. FePOST and FeKIM-1 also correlated strongly with tubular protein markers. The FePOST/FeKIM-1 ratio was elevated in ES patients compared with controls and remained stable across CKD stages. Fractional excretion of POST and KIM-1 is associated with CKD stage and reflects ongoing tubular injury in children. The FePOST/FeKIM-1 ratio may represent a sensitive marker of early CKD.

Periostin (POSTN) is a critical extracellular matrix protein in various tumor microenvironments. However, the function of POSTN in thyroid cancer progression remains largely unknown. and knock-out mice and orthotopic mouse models were used to determine the role of POSTN on papillary thyroid tumor progression. Immunofluorescence, cell co-culture, fluorescence hybridization, chromatin immunoprecipitation assay, recombinant protein and inhibitor treatment were performed to explore the underlying mechanisms of POSTN-promoted papillary thyroid tumor growth. POSTN is up-regulated in papillary thyroid tumors and negatively correlates with the overall survival of patients with thyroid cancer. Cancer-associated fibroblast (CAF)-derived POSTN promotes papillary thyroid tumor growth and . POSTN deficiency in CAFs significantly impairs CAF-promoted papillary thyroid tumor growth. POSTN promotes papillary thyroid tumor cell proliferation and IL-4 expression through integrin-FAK-STAT3 signaling. In turn, tumor cell-derived IL-4 induces the activation of CAFs and stimulates POSTN expression by activating STAT6. We reveal the crucial role of CAF-derived POSTN and tumor cell-derived IL-4 in driving the development of papillary thyroid tumors through the POSTN-integrin-FAK-STAT3-IL-4 pathway in tumor cells and IL-4-STAT6-POSTN signaling in CAFs. Our findings underscore the significance of POSTN and IL-4 as critical molecular mediators in the dynamic interplay between CAFs and tumor cells, ultimately supporting the growth of papillary thyroid tumors.

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.

Background Ovarian cancer has the highest mortality among gynecological cancers due to late diagnosis and lack of effective targeted therapy. Although the study of interplay between cancer cells with their microenvironment is emerging, how ovarian cancer triggers signaling that coordinates with immune cells to promote metastasis is still elusive. Methods Microarray and bioinformatics analysis of low and highly invasive ovarian cancer cell lines were used to reveal periostin (POSTN), a matrix protein with multifunctions in cancer, with elevated expression in the highly invasive cells. Anchorage independent assay, Western blot, RNA interference, confocal analysis and neutralizing antibody treatment were performed to analyze the effects of POSTN on tumor promotion and to explore the underlying mechanism. Chemotaxis, flow cytometry and cytokine array analyses were undertaken to analyze the involvement of POSTN in cancer-associated fibroblast (CAF) and macrophage modulation. Correlations between POSTN expression levels and clinical characteristics were analyzed using the Oncomine, commercial ovarian cancer cDNA and China Medical University Hospital patient cohort. In vivo effect of POSTN on metastasis was studied using a mouse xenograft model. Results Expression of POSTN was found to be elevated in highly invasive ovarian cancer cells. We observed that POSTN was co-localized with integrin β3 and integrin β5, which was important for POSTN-mediated activation of ERK and NF-κB. Ectopic expression of POSTN enhanced whereas knockdown of POSTN decreased cancer cell migration and invasion in vitro, as well as tumor growth and metastasis in vivo. POSTN enhanced integrin/ERK/NF-κB signaling through an autocrine effect on cancer cells to produce macrophage attracting and mobilizing cytokines including MIP-1β, MCP-1, TNFα and RANTES resulting in increased chemotaxis of THP-1 monocytes and their polarization to M2 macrophages in vitro. In agreement, tumors derived from POSTN-overexpressing SKOV3 harbored more tumor-associated macrophages than the control tumors. POSTN induced TGF-β2 expression from ovarian cancer cells to promote activation of adipose-derived stromal cells to become CAF-like cells expressing alpha smooth muscle actin and fibroblast activation protein alpha. Consistently, increased CAFs were observed in POSTN overexpressing SKOV3 cells-derived metastatic tumors. In clinical relevance, we found that expression of POSTN was positively correlated with advanced-stage diseases and poor overall survival of patients. Conclusions Our study revealed a POSTN-integrin-NF-κB-mediated signaling and its involvement in enhancing M2 macrophages and CAFs, which could potentially participate in promoting tumor growth. Our results suggest that POSTN could be a useful prognosis marker and potential therapeutic target.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease characterized by heterogeneous phenotypes and endotypes, necessitating personalized therapeutic strategies. Precision medicine approaches integrating molecular biomarkers may improve treatment selection and disease stratification. In this prospective controlled study, we investigated the tissue-level immunohistochemical effects of oral corticosteroids (OCSs) and topical steroids on the expression of periostin, eotaxin, interleukin-4 (IL-4), transforming growth factor-β (TGF-β), and tumor necrosis factor-α (TNF-α) in nasal polyp tissue. Sixty-five patients eligible for endoscopic sinus surgery (ESS) were enrolled and divided into two groups: Group 1 (n = 42) received topical steroids combined with oral prednisone (40 mg/day for 7 days preoperatively), whereas Group 2 (n = 23) received topical steroids alone. Immunohistochemical analysis demonstrated a significant reduction in periostin and eotaxin expression in both epithelial and stromal compartments following OCS therapy, accompanied by increased TGF-β expression. No significant differences were observed in IL-4 or TNF-α expression. These findings indicate that short-term OCSs selectively modulate molecular pathways associated with eosinophilic inflammation and tissue remodeling in CRSwNP, supporting biomarker-driven precision medicine strategies.

Idiopathic pulmonary fibrosis (IPF) is a devastating interstitial lung disease characterized by the excessive accumulation of activated myofibroblasts that deposit extracellular matrix (ECM) protein, leading to progressive scar formation and mechanical stress. However, the cellular origin and fate of myofibroblasts remain controversial, and the mechanisms by which myofibroblasts sense mechanical cues in the lung are unclear. Here, we report that periostin (Postn) is a reliable and distinctive marker for pulmonary myofibroblasts, while ablation of Postn + myofibroblasts after injury ameliorated lung fibrosis. PIEZO1 was highly expressed in Postn + myofibroblast and played a vital role in mechanoactivation of Postn + myofibroblast and development of lung fibrosis. Conditional deletion of Piezo1 in Postn + myofibroblasts significantly inhibited lung fibrosis by suppressing myofibroblast activation and proliferation. Loss of Piezo1 led to disruption of actin organization and prevention of Yap/Taz nuclear localization, thus shifting the myofibroblasts from a proliferative state into a stressed and apoptotic state. Furthermore, myofibroblast-specific Yap/Taz deletion fully recapitulated the protective phenotypes of myofibroblast- Piezo1 –KO mice. These findings show that periostin marks pulmonary myofibroblasts, and that PIEZO1-mediated mechanosensation is essential for myofibroblast activation in the lung. Targeting PIEZO1 in the periostin-expressing cells is a novel therapeutic option to interfere with fibrotic diseases such as IPF .

Periostin (POSTN), a member of the matricellular protein family, is a secreted adhesion-related protein produced in the periosteum and periodontal ligaments. Matricellular proteins are a nonstructural family of extracellular matrix (ECM) proteins that regulate a wide range of biological processes in both normal and pathological conditions. Recent studies have demonstrated the key roles of these ECM proteins in the tumor microenvironment. Furthermore, periostin is an essential regulator of bone and tooth formation and maintenance, as well as cardiac development. Also, periostin interacts with multiple cell-surface receptors, especially integrins, and triggers signals that promote tumor growth. According to recent studies, these signals are implicated in cancer cell survival, epithelial-mesenchymal transition (EMT), invasion, and metastasis. In this review, we will summarize the most current data regarding periostin, its structure and isoforms, expressions, functions, and regulation in normal and cancerous tissues. Emphasis is placed on its association with cancer progression, and also future potential for periostin-targeted therapeutic approaches will be explored.

There are many downstream targets of mitogen-activated protein kinase (MAPK) signalling that are involved in neuronal development, cellular differentiation, cell migration, cancer, cardiovascular dysfunction and inflammation via their functions in promoting apoptosis and cell motility and regulating various cytokines. It has been reported that cyclic AMP response element-binding protein (CREB) is phosphorylated and activated by cyclic AMP signalling and calcium/calmodulin kinase. Recent evidence also points to CREB phosphorylation by the MAPK signalling pathway. However, the specific roles of CREB phosphorylation in MAPK signalling have not yet been reviewed in detail. Here, we describe the recent advances in the study of this MAPK-CREB signalling axis in human diseases. Overall, the crosstalk between extracellular signal-related kinase (ERK) 1/2 and p38 MAPK signalling has been shown to regulate various physiological functions, including central nervous system, cardiac fibrosis, alcoholic cardiac fibrosis, osteoclast differentiation, mucin production in the airway, vascular smooth muscle cell migration, steroidogenesis and asthmatic inflammation. In this review, we focus on ERK1/2 and/or p38 MAPK-dependent CREB activation associated with various diseases to provide insights for basic and clinical researchers.