Pathology, research and practice最新文献

{"title":"Beyond the brain: Reelin's emerging role in cancer pathways","authors":"Chou-Yi Hsu ,&nbsp;Ghufran Lutfi Ismaeel ,&nbsp;Oras Kadhim ,&nbsp;Zaid Dahnoon Hadi ,&nbsp;Mahmood Hasen Shuhata Alubiady ,&nbsp;Mohammed Qasim Alasheqi ,&nbsp;Mohammed Shnain Ali ,&nbsp;Montather F. Ramadan ,&nbsp;Salah Hassan Zain Al-Abdeen ,&nbsp;Khursheed Muzammil ,&nbsp;Halah Majeed Balasim ,&nbsp;Ahmed hussien Alawady","doi":"10.1016/j.prp.2025.155901","DOIUrl":"10.1016/j.prp.2025.155901","url":null,"abstract":"<div><div>The glycoprotein Reelin is essential for neuronal migration during embryonic development and is involved in various cellular processes. It interacts with specific lipoprotein receptors to regulate neuronal migration and synaptic plasticity. Recent research has expanded our understanding of Reelin's functions, revealing its involvement in processes such as cell proliferation, activation, migration, platelet aggregation, and vascular development. Reelin's influence extends beyond neurodevelopment, with abnormal expression observed in several cancer types. This suggests a potential connection between Reelin dysregulation and tumor formation. Altered Reelin levels correlate with increased tumor aggressiveness, metastatic potential, and poor patient outcomes. In cancer, Reelin affects key cellular processes including proliferation, migration, and invasion. Evidence indicates that Reelin modulates important signaling pathways like PI3K/Akt and MAPK, contributing to the development of cancer hallmarks. Its interactions with integrins and matrix metalloproteinases imply a role in shaping the tumor microenvironment, thereby influencing cancer progression. These findings highlight Reelin's dual significance in neurodevelopment and cancer biology. Further investigation into Reelin's complex functions could lead to new diagnostic tools and therapeutic approaches, potentially advancing cancer treatment through targeted research on its signaling mechanisms. This review provides a condensed overview of Reelin's multifaceted roles in both neurodevelopment and cancer.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155901"},"PeriodicalIF":2.9,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143593110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Knockout of Trpc6 attenuates T2DM-induced liver injury and inflammation by inhibiting CN-NFAT2-NLRP3 signalling in mice","authors":"Yan Liu ,&nbsp;Yinglin Fu ,&nbsp;Guohang Wang ,&nbsp;Yong Su ,&nbsp;Ran Sun ,&nbsp;Huimin Zhou ,&nbsp;Pengmin Ji ,&nbsp;Hanyang Xu ,&nbsp;Weiping Li ,&nbsp;Weizu Li","doi":"10.1016/j.prp.2025.155894","DOIUrl":"10.1016/j.prp.2025.155894","url":null,"abstract":"<div><div>Diabetic liver disease is a common complication of diabetes mellitus that poses significant harm to patients. Transient receptor potential cation channel 6 (TRPC6) is a non-selective cation channel with calcium permeability, playing a key role in signalling pathways associated with liver disease progression. This study aimed to investigate the effects of <em>Trpc6</em> knockout on liver injury and its regulation of the calcineurin (CN)-nuclear factor of activated T cells 2 (NFAT2) signalling pathway in mice with type 2 diabetes mellitus (T2DM). Serum aspartate aminotransferase and alanine aminotransferase levels were measured to assess liver function, while haematoxylin and eosin staining, periodic acid-Schiff staining, and Masson staining were used to evaluate pathological injury. Nile Red and Oil Red O staining were performed to assess hepatic lipid deposition. Western blotting, quantitative real-time polymerase chain reaction, and immunohistochemistry were used to analyse fibrosis- and inflammation-related markers in mouse liver tissues. The results showed that <em>Trpc6</em> knockout had no significant effect on hepatic lipid deposition, CD36 expression, or phosphorylated phospholipase C levels in the liver tissues of mice with T2DM. However, <em>Trpc6</em> knockout significantly inhibited NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome activation, thereby alleviating liver injury and fibrosis in mice with T2DM. Further findings indicated that <em>Trpc6</em> knockout markedly reduced CN and NFAT2 expression in T2DM liver tissues and resisted intracellular calcium overload in liver cells <em>in vitro</em>. This study suggests that <em>Trpc6</em> knockout attenuates T2DM-induced hepatic inflammation and fibrosis by inhibiting hepatocyte calcium overload and suppressing the CN-NFAT2-NLRP3 signalling pathway.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155894"},"PeriodicalIF":2.9,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143579541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FAM72 family members serves as prognostic biomarker in liver hepatocellular carcinoma","authors":"Naer A,&nbsp;Feilong Zou,&nbsp;Meiyan Chen,&nbsp;Meiling Liu,&nbsp;Huishan Zhang,&nbsp;Shaohua Cheng ,&nbsp;Yunhong Liu","doi":"10.1016/j.prp.2025.155893","DOIUrl":"10.1016/j.prp.2025.155893","url":null,"abstract":"<div><h3>Background</h3><div>Liver hepatocellular carcinoma (LIHC) is a common cancer with poor prognosis. The FAM72 gene family enhances neuronal self-renewal, potentially increasing tumor formation, but its functional and predictive relevance in LIHC remains unclear. We sought to investigate the function of the FAM72 gene family in LIHC in the present study.</div></div><div><h3>Methods</h3><div>We acquired TCGA-LIHC expression and phenotypic data as well as extensive clinicopathologic information from the UCSC Xena Database (<span><span>https://xenabrowser.net/datapages/</span><svg><path></path></svg></span>) database. We analyzed the association between FAM72 gene family expression in LIHC and patient prognosis and immune infiltration; Genomic and functional enrichment analysis for FAM72 genes was analyzed. Finally, Western blot method, quantitative real-time polymerase chain reaction and CCK8 detection and cell invasion experiments were used to verify the effect of FAM72A expression on LIHC.</div></div><div><h3>Results</h3><div>The expression of FAM72 gene family is different between LIHC and normal liver tissues. The expression of FAM72 gene family increased with increasing grading of LIHC tissues. The expression of FAM72 gene family was significantly reduced in LIHC stage IV. LIHC tissues expressed significantly more FAM72 genes than did normal tissues at the T stage (p &lt; 0.001,). which has a good value in the diagnosis of LIHC (AUC greater than 0.85), and was strongly linked with the tumor stage in LIHC. Based on Cox analysis of univariate data, the FAM72 gene family was associated with poor overall survival (OS) in patients with LIHC. Analysis of multifactorial Cox data revealed an independent relationship between FAM72 expression and OS. Increased FAM72 gene expression is associated with poor survival rates and immune cell infiltration. Methylation levels were associated with the prognosis of patients with LIHC. Ultimately, our findings revealed that FAM72A is abundantly expressed in LIHC cells, facilitating proliferation and metastasis.</div></div><div><h3>Conclusion</h3><div>These findings indicate that the FAM72 gene family is a potential molecular marker for poor prognosis in LIHC, providing additional insights into the development of therapeutic approaches and prognostic markers.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155893"},"PeriodicalIF":2.9,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143611118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell lineage-specific immunohistochemical markers in biliary intraepithelial neoplasia: Implications for subclassification and grading","authors":"Heiwa Tanabe ,&nbsp;Takeshi Uehara ,&nbsp;Hiroyoshi Ota","doi":"10.1016/j.prp.2025.155896","DOIUrl":"10.1016/j.prp.2025.155896","url":null,"abstract":"<div><div>Biliary intraepithelial neoplasia (BilIN), a precursor to cholangiocarcinoma, is categorized into low- and high-grade based on histological characteristics. Although gastric, intestinal, and biliary phenotypes of BilIN have been identified, detailed analyses of their immunophenotypic profiles using cell lineage-specific markers remain limited. This study aimed to define the immunohistochemical profiles of BilIN lesions, subclassify them based on their immunophenotypes, and correlate these profiles with histological grades. We examined 77 BilIN lesions from extrahepatic bile ducts, including 30 low- and 47 high-grade lesions, using immunohistochemical staining for gastric (claudin-18, MUC5AC), intestinal (cadherin-17, glycoprotein A33), and biliary (carbohydrate sulfotransferase 4) markers, along with progression markers (S100P, IMP3). Expression levels were semiquantitatively scored and correlated with histopathological features. BilIN lesions were classified into four immunophenotypes: gastric (G-type), intestinal (I-type), gastrointestinal (GI-type), and biliary (B-type). Low-grade lesions comprised G- (33.3 %), GI- (40 %), I- (13.3 %), and B-types (13.3 %), while high-grade lesions included G- (40.4 %), GI- (29.8 %), I- (21.3 %), and B-types (8.5 %). In low-grade BilIN, G-type lesions corresponded to gastric mucous cells, I-type to intestinal epithelial cells, and B-type to bile duct epithelial cells, while most GI-type lesions exhibited mixed G- and I-type components. High-grade BilIN differentiation based solely on histological characteristics was challenging to delineate due to overlapping features among I-, GI-, and B-type cells. S100P and IMP3 expression levels were significantly elevated in high-grade lesions, particularly within the I+B-type BilIN group, with no notable differences in G- or GI-type BilIN. Immunophenotypic profiling with lineage-specific markers effectively subclassified BilIN, enhancing the understanding of its histogenesis and progression.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155896"},"PeriodicalIF":2.9,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143563438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"XBP1: A key regulator in breast cancer development and treatment","authors":"Ya-Ya Wang ,&nbsp;Sheng-Kai Geng ,&nbsp;Yi-Peng Fu,&nbsp;Jian Sun","doi":"10.1016/j.prp.2025.155900","DOIUrl":"10.1016/j.prp.2025.155900","url":null,"abstract":"<div><div>X-box binding protein 1 (XBP1), as a transcription factor, plays pivotal role in unfolded protein response (UPR), which is activated in response to endoplasmic reticulum (ER) stress to restore ER homeostasis. IRE1α/XBP1 pathway is a key component of UPR, and the expression levels of XBP1 can dictate the fate of cells under ER stress, either promoting survival or driving apoptosis. High expression of XBP1 in breast tumors is closely associated with poor prognosis. The paper elucidates the biological functions of XBP1 and its involvement in UPR, while also surveying the latest research on how XBP1 influences immunity, metabolism, apoptosis, angiogenesis, and the invasive and migratory behaviors of breast cancer cells. Moreover, it contemplates the potential of XBP1 as a therapeutic target for breast cancer treatment.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155900"},"PeriodicalIF":2.9,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143619682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A floating collagen matrix triggers ring formation and stemness characteristics in human colorectal cancer organoids","authors":"Daniel Gerhard Wimmers ,&nbsp;Kerstin Huebner ,&nbsp;Trevor Dale ,&nbsp;Aristeidis Papargyriou ,&nbsp;Maximilian Reichert ,&nbsp;Arndt Hartmann ,&nbsp;Regine Schneider-Stock","doi":"10.1016/j.prp.2025.155890","DOIUrl":"10.1016/j.prp.2025.155890","url":null,"abstract":"<div><div>Intestinal organoids reflect the 3D structure and function of their original tissues. Organoid are typically cultured in Matrigel, an extracellular matrix (ECM) mimicking the basement membrane, which is suitable for epithelial cells but does not accurately mimic the tumour microenvironment of colorectal cancer (CRC). The ECM and particularly collagen type I is crucial for CRC progression and invasiveness. Given that efforts to examine CRC organoid invasion in a more physiologically relevant ECM have been limited, we used a floating collagen type I matrix (FC) to study organoid invasion in three patient-derived CRC organoid lines. In FC gel, organoids contract, align, and fuse into macroscopic ring structures, initiating minor branch formation and invasion fronts, phenomena unique for the collagen ECM and otherwise not observed in Matrigel-grown CRC organoids. In contrast to Matrigel, FC organoids showed basal extrusion with improper actin localization, but without change in the organoid polarity. Moreover, small clusters of vital invading cells were observed. Gene expression analysis revealed that the organoids cultured in a FC matrix presented more epithelial and stem cell-like characteristics. This novel technique of cultivating CRC organoids in a FC matrix represents an <em>in-vitro</em> model for studying cancer organization and matrix remodelling with increased organoid stemness potential.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155890"},"PeriodicalIF":2.9,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143593112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intracytoplasmic accumulation of keratan sulfate is a hallmark of granular cell tumor","authors":"Hitomi Hoshino ,&nbsp;Akifumi Muramoto ,&nbsp;Tomoya O. Akama ,&nbsp;Hisato Yoshida ,&nbsp;Natsumi Yonemoto ,&nbsp;Mana Fukushima ,&nbsp;Motohiro Kobayashi","doi":"10.1016/j.prp.2025.155892","DOIUrl":"10.1016/j.prp.2025.155892","url":null,"abstract":"<div><div>Granular cell tumor (GCT) is a relatively rare neoplasm characterized by abundant eosinophilic intracytoplasmic granules. More than three decades ago, Ehara and Katsuyama reported that GCT granules are recognized by the anti-keratan sulfate (KS) monoclonal antibody 5D4 and suggested that 5D4 could serve as a diagnostic marker for GCT. However, due to the small number of samples analyzed and incomplete structural analysis of KS, use of 5D4 as a GCT marker has not yet been widely accepted. To confirm its use as a GCT marker, we performed quantitative immunohistochemical analysis of GCT (<em>n</em> = 27) and other GCT-mimicking tumors/lesions (<em>n</em> = 82) including schwannoma (<em>n</em> = 10), neurofibroma (<em>n</em> = 10), melanocytic nevus (<em>n</em> = 10), leiomyoma (<em>n</em> = 10), gastrointestinal stromal tumor (GIST) (<em>n</em> = 10), malignant melanoma (<em>n</em> = 10), dermatofibroma (<em>n</em> = 10), angiosarcoma (<em>n</em> = 10) and malakoplakia (<em>n</em> = 2) using 5D4 and two other anti-KS monoclonal antibodies, R-10G and 297–11A, in combination with two endoglycosidases, keratanase II and endo-β-galactosidase. We found that most GCT tissues were immunostained with 5D4 and 297–11A, although tumors/lesions mimicking GCT showed minimal staining. Moreover, structural analysis revealed that KS accumulated in GCT consisted of both highly sulfated and low-sulfated KS located at non-reducing and reducing termini, respectively. Here we propose that intracytoplasmic KS accumulation is a hallmark of GCT, and that 5D4 and 297–11A could serve as diagnostic markers of GCT.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155892"},"PeriodicalIF":2.9,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143550998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Schizandrin A promotes apoptosis in prostate cancer by inducing ROS-mediated endoplasmic reticulum stress and JNK MAPK signaling activation","authors":"Chang-wei Peng ,&nbsp;Pei-li Ma ,&nbsp;Hai-tao Dai","doi":"10.1016/j.prp.2025.155889","DOIUrl":"10.1016/j.prp.2025.155889","url":null,"abstract":"<div><h3>Background</h3><div>Prostate cancer (PCa) is the most common malignant tumor in males with limited therapies. Schizandrin A (SchA) is a biologically active lignan isolated from the fruit of <em>Schisandra chinensis</em>. This research aimed to evaluate the roles and mechanisms of SchA in the progression of PCa.</div></div><div><h3>Methods</h3><div>PCa cells (VCap and DU145) treated with or without SchA were subjected to MTT assays, colony formation assays, DCFH-DA assays, western blotting, TUNEL staining, and flow cytometry analyses of cell cycle, cell apoptosis, and JC-1. Tumor xenograft model was established in nude mice to assess the in vivo effect of SchA.</div></div><div><h3>Results</h3><div>SchA suppressed cell proliferation and induced cell cycle arrest at G2/M and apoptosis in PCa cells. Additionally, SchA enhanced ROS generation and endoplasmic reticulum stress and activated JNK signaling to induce PCa apoptosis. Furthermore, SchA suppressed tumor growth in vivo.</div></div><div><h3>Conclusion</h3><div>SchA induces cell cycle arrest and apoptosis in PCa cells by activating ROS-mediated ER stress and JNK MAPK signaling.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155889"},"PeriodicalIF":2.9,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143611119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring immune checkpoint inhibitors: Focus on PD-1/PD-L1 axis and beyond","authors":"Durre Aden ,&nbsp;Samreen Zaheer ,&nbsp;Niti Sureka ,&nbsp;Monal Trisal ,&nbsp;Jai Kumar Chaurasia ,&nbsp;Sufian Zaheer","doi":"10.1016/j.prp.2025.155864","DOIUrl":"10.1016/j.prp.2025.155864","url":null,"abstract":"<div><div>Immunotherapy emerges as a promising approach, marked by recent substantial progress in elucidating how the host immune response impacts tumor development and its sensitivity to various treatments. Immune checkpoint inhibitors have revolutionized cancer therapy by unleashing the power of the immune system to recognize and eradicate tumor cells. Among these, inhibitors targeting the programmed cell death protein 1 (PD-1) and its ligand (PD-L1) have garnered significant attention due to their remarkable clinical efficacy across various malignancies. This review delves into the mechanisms of action, clinical applications, and emerging therapeutic strategies surrounding PD-1/PD-L1 blockade. We explore the intricate interactions between PD-1/PD-L1 and other immune checkpoints, shedding light on combinatorial approaches to enhance treatment outcomes and overcome resistance mechanisms. Furthermore, we discuss the expanding landscape of immune checkpoint inhibitors beyond PD-1/PD-L1, including novel targets such as CTLA-4, LAG-3, TIM-3, and TIGIT. Through a comprehensive analysis of preclinical and clinical studies, we highlight the promise and challenges of immune checkpoint blockade in cancer immunotherapy, paving the way for future advancements in the field.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155864"},"PeriodicalIF":2.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143579542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The m6A reader YTHDC2 restrains endometrial cancer progression through suppressing hedgehog signaling pathway","authors":"Xinyan Zhang ,&nbsp;Man Gao ,&nbsp;Hongyun Ma ,&nbsp;Zhao Ma ,&nbsp;Tengqi Wang ,&nbsp;Wen Gao ,&nbsp;Qin Si ,&nbsp;Ning Li ,&nbsp;Yongping Mu ,&nbsp;Fei Liu","doi":"10.1016/j.prp.2025.155879","DOIUrl":"10.1016/j.prp.2025.155879","url":null,"abstract":"<div><div>N6-methyladenosine (m⁶A) is a prevalent RNA modification involved in different physiological and pathological processes. However, little is known about the role of m⁶A modification in endometrial cancer (EC). In this study, we explored the expression and prognosis of m⁶A-related genes in EC using public databases to screen relevantgenes. Quantitative reverse-transcription PCR and immunohistochemistry were performed to detect YTH N6-methyladenosine RNA binding protein C2 (YTHDC2) expression in EC tissues, and the relationships between YTHDC2 expression, pathological features, and prognosis were analyzed. The effect of YTHDC2 on EC cells and its mechanism of action were examined in vitro and in vivo. YTHDC2 was identified as a tumor suppressor gene in EC. Expression of YTHDC2 mRNA and protein was significantly lower in EC tissues than in normal tissues. YTHDC2 expression was related to myometrial invasion (χ²=7.523, <em>P</em> = 0.006), lymph node metastasis (χ²=7.203, <em>P</em> = 0.007), and FIGO stage (χ²=9.678, <em>P</em> = 0.008) in EC. It was also a prognostic factor in EC (95 %CI: 1.217–3.646, <em>P</em> = 0.013), and patients with EC low YTHDC2 expression had poor overall survival. YTHDC2 knockdown promoted the proliferation, migration, and invasion of EC cells, and decreased apoptosis. Upregulation of YTHDC2 showed the opposite effects. YTHDC2 inhibited the Hedgehog signaling pathway, and the Hedgehog inhibitor vismodegib partly eliminated the effects of YTHDC2 knockdown of EC cells. YTHDC2 inhibited EC progression and has the potential to be explored as an independent prognostic factor in patients with EC.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155879"},"PeriodicalIF":2.9,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143551072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}