Pathology, research and practice最新文献

{"title":"ZEB1-upregulated LCN2 via transcription regulation affects ferroptosis and malignant progression in non-small cell lung cancer.","authors":"Qiang Zhou, Wei Zhang, Jun Huang, Wenbing Hu","doi":"10.1016/j.prp.2025.156154","DOIUrl":"10.1016/j.prp.2025.156154","url":null,"abstract":"<p><p>Ferroptosis exerts a remarkable influence on the progression of non-small cell lung cancer (NSCLC). Although the contribution of lipocalin 2 (LCN2) to NSCLC pathogenesis has been demonstrated, further elucidation of the molecular determinants driving LCN2 dysregulation is essential for developing NSCLC interventions. mRNA levels were performed by quantitative polymerase chain reaction (PCR), and protein expression was assessed by immunoblotting and immunohistochemical assays. Reactive oxygen species (ROS), glutathione (GSH), malondialdehyde (MDA), and Fe^2 + levels were measured to analyze cell ferroptosis. The relationship between zinc-finger E-box-binding homeobox 1 (ZEB1) and the LCN2 promoter was verified by chromatin immunoprecipitation (ChIP) and luciferase assays. Our data showed that LCN2 and ZEB1 levels were upregulated in NSCLC. LCN2 depletion reduced the growth, motility, and invasiveness of NSCLC cells, while promoting apoptosis and ferroptosis. LCN2 depletion also inhibited the tube formation of human umbilical vein endothelial cells (HUVECs) in vitro. Mechanistically, ZEB1 enhanced the transcription and expression of LCN2 in NSCLC cells. ZEB1 downregulation diminished HUVEC tube formation, suppressed the growth, motility, and invasiveness of NSCLC cells, and enhanced apoptosis and ferroptosis. Notably, these effects were counteracted by re-expression of LCN2. Additionally, ZEB1 downregulation inhibited the growth of xenograft tumors in vivo. Our study demonstrates the pro-tumorigenic role of the ZEB1/LCN2 cascade in NSCLC by promoting malignant progression and impeding ferroptosis. Such molecular insights may help devise novel candidates for NSCLC treatment.</p>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"274 ","pages":"156154"},"PeriodicalIF":3.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812259","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 nomogram integrating M2 macrophages and extracellular matrix components outperforms TNM classification in pulmonary sarcomatoid carcinoma prognosis: A two-center retrospective study.","authors":"Chao Ma, Yaoying Li, Chengyou Zheng, Suijing Wang, Yuanqing Zhang, Haibo Wu, Zhengyi Zhou, Jierong Chen, Keming Chen, Xinke Zhang, Yangfan He, Junpeng Lai, Jiewei Chen","doi":"10.1016/j.prp.2025.156161","DOIUrl":"10.1016/j.prp.2025.156161","url":null,"abstract":"<p><strong>Objective: </strong>Tumor microenvironment composition significantly influences tumor progression. This study aimed to explore the distribution of M2 tumor-associated macrophages (TAMs), reticular fibers (RFs), and collagen fibers (CFs) within the tumor microenvironment of pulmonary sarcomatoid carcinoma (PSC) and assess their clinicopathological significance.</p><p><strong>Methods: </strong>Formalin-fixed paraffin tissue sections of 127 PSC patients from two medical centers were collected and analyzed by immunohistochemistry and the Gomori method. HALO software was used to analyze the distributions of M₂TAMs, RFs, and CFs, and statistically analyzed for clinicopathological significance.</p><p><strong>Results: </strong>Kaplan-Meier analysis showed that overall survival (OS) was longer in patients with low density of M₂TAMs (P = 0.038) and high density of CFs (P = 0.046) and RFs (P = 0.010). Patients classified within the low-risk group, based on the combined factors MR and MC, experienced significantly longer OS than those in the high-risk group. Multivariate analysis identified the densities of M₂TAMs, RFs, and CFs, along with MC and MR, as independent prognostic factors for patient OS. Nomogram models 1 and 2, with C-indices of 0.74 and 0.73, respectively, were highly effective in predicting OS. Decision curve analysis demonstrated that the Nomogram model outperformed pTNM staging in predicting medium- and long-term survival.</p><p><strong>Conclusion: </strong>High densities of M₂TAMs and low densities of RFs and CFs are associated with poor prognosis in PSC patients and are independent prognostic factors. The Nomogram model proved was more effective than pTNM staging in predicting medium- and long-term survival, offering a valuable tool for the individualized clinical treatment of PSC patients.</p>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"274 ","pages":"156161"},"PeriodicalIF":3.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812257","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":"Evaluation of general-purpose large language models as diagnostic support tools in cervical cytology.","authors":"Thiyaphat Laohawetwanit, Sompon Apornvirat, Aleksandra Asaturova, Hua Li, Kris Lami, Andrey Bychkov","doi":"10.1016/j.prp.2025.156159","DOIUrl":"10.1016/j.prp.2025.156159","url":null,"abstract":"<p><strong>Introduction: </strong>The application of general-purpose large language models (LLMs) in cytopathology remains largely unexplored. This study aims to evaluate the accuracy and consistency of a custom version of ChatGPT-4 (GPT), ChatGPT o3, and Gemini 2.5 Pro as diagnostic support tools for cervical cytology.</p><p><strong>Materials and methods: </strong>A total of 200 Papanicolaou-stained cervical cytology images were acquired at 40x magnification, each measuring 384 × 384 pixels. These images consisted of 100 cases classified as negative for intraepithelial lesion or malignancy (NILM) and 100 cases across various abnormal categories: 20 low-grade squamous intraepithelial lesion (LSIL), 20 high-grade squamous intraepithelial lesion (HSIL), 20 squamous cell carcinoma (SCC), 20 adenocarcinoma in situ (AIS), and 20 adenocarcinoma (ADC). Diagnostic accuracy and consistency were evaluated by submitting each image to a GPT, ChatGPT o3, and Gemini 2.5 Pro 5-10 times.</p><p><strong>Results: </strong>When distinguishing normal from abnormal cytology, LLMs showed mean sensitivity between 85.4 % and 100 %, and specificity between 67.2 % and 92.7 %. ChatGPT o3 was more accurate in identifying NILM (mean 89.2 % vs. 67.2 %) but less accurate in detecting LSIL (34 % vs. 85 %), HSIL (6 % vs. 63 %), and ADC (28 % vs. 91 %). Chain-of-thought prompting and submitting multiple images of the same diagnosis to ChatGPT o3 and Gemini 2.5 Pro did not significantly improve accuracy. Both models also performed poorly in identifying cervicovaginal infections.</p><p><strong>Conclusions: </strong>ChatGPT o3 and Gemini 2.5 Pro demonstrated complementary strengths in cervical cytology. Due to their low accuracy and inconsistency in abnormal cytology, general-purpose LLMs are not recommended as diagnostic support tools in cervical cytology.</p>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"274 ","pages":"156159"},"PeriodicalIF":3.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144817332","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":"Refining HER2-Negative breast cancer: distinct survival profiles of HER2-Low and HER2-Ultralow tumors.","authors":"Dido Eliphas Leão de Alencar, Giuliano Rizzotto Guimarães, Adriana Vial Roehe","doi":"10.1016/j.prp.2025.156140","DOIUrl":"10.1016/j.prp.2025.156140","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the clinical, pathological, and prognostic significance of HER2-low and HER2-ultralow expression in breast cancer.</p><p><strong>Methods: </strong>In this retrospective study, 171 HER2-negative breast cancer cases were reclassified by immunohistochemistry as HER2-low, HER2-ultralow, or HER2 IHC 0. Clinicopathological variables, Ki-67 index, hormone receptor (HR) status, and treatment data were analyzed. Welch's ANOVA, Kaplan-Meier survival with a 60-month landmark, and Cox regression were applied.</p><p><strong>Results: </strong>The cohort included 49.1 % HER2-low, 27.5 % HER2-ultralow, and 23.4 % HER2 IHC 0 cases. No significant differences were found in clinical stage, histologic grade, or treatment distribution. Ki-67 index was lower in HER2 IHC 0 tumors (p = 0.047). Overall survival (OS) differed significantly: HER2-ultralow patients had the best outcomes (median OS: 47.5 months), followed by HER2 IHC 0 (37.5) and HER2-low (33.0) (log-rank p < 0.05). In multivariable Cox analysis, HER2-low status was independently associated with worse OS versus HER2-ultralow (HR = 1.86; p = 0.006), while HER2 IHC 0 showed no significant difference (HR = 1.42; p = 0.212). Higher Ki-67 and negative ER status were also linked to worse prognosis. Subgroup analysis revealed the poorest outcomes in HER2-low/HR-negative tumors.</p><p><strong>Conclusion: </strong>HER2-ultralow tumors were associated with better survival than HER2-low, suggesting clinical relevance in further subclassifying HER2-negative breast cancers. Although the retrospective design and minor proportional hazard violations warrant caution, these findings may guide treatment for more individualized approaches. Future multicenter studies, supported by molecular profiling and AI-assisted HER2 scoring, are essential to validate these findings and improve reproducibility in low-level HER2 assessment.</p>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"274 ","pages":"156140"},"PeriodicalIF":3.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812258","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":"Association of vitamin D receptor gene polymorphisms in gastrointestinal cancer: A systematic review and meta-analysis.","authors":"Hongyu Wang, Yawen Yang, Juan Du","doi":"10.1016/j.prp.2025.156155","DOIUrl":"10.1016/j.prp.2025.156155","url":null,"abstract":"<p><strong>Background: </strong>Gastrointestinal cancers (GICs), encompassing malignancies of the esophagus, stomach, and colorectal regions, are among the most prevalent cancers worldwide. Given the inconsistent and heterogeneous findings across studies, this meta-analysis aims to comprehensively assess the association between vitamin D receptor (VDR) gene polymorphisms and the risk of GICs.</p><p><strong>Methods: </strong>A systematic search was conducted in MEDLINE, Web of Science, Scopus, and Embase to identify relevant studies investigating the association between VDR polymorphisms and GIC risk. After removing duplicates, studies were screened based on predefined inclusion and exclusion criteria. Data analysis was performed using Comprehensive Meta-Analysis software (version 2). Publication bias was evaluated using Egger's test, and study heterogeneity was assessed using the I² statistic. Pooled odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated.</p><p><strong>Results: </strong>A total of 51 studies were included in the meta-analysis. Significant associations were found between gastric cancer and the FokI polymorphism (ff vs. FF: OR = 1.58; FF+Ff vs. ff: OR = 0.52), as well as the TaqI polymorphism (tt vs. TT: OR = 1.70). For colorectal cancer (CRC), the BsmI variant showed consistent associations in the recessive, heterozygous, and allelic models, even after excluding studies not in Hardy-Weinberg equilibrium. No significant associations were observed for Cdx2 or in relation to esophageal cancer. Subgroup and meta-regression analyses revealed age- and region-specific effects.</p><p><strong>Conclusion: </strong>VDR gene polymorphisms, particularly FokI and TaqI, are significantly associated with gastric cancer risk, while BsmI is linked to increased susceptibility to CRC. No associations were observed for esophageal cancer. These results support the potential role of genetic variants in gastrointestinal carcinogenesis and warrant further validation in diverse populations.</p>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"274 ","pages":"156155"},"PeriodicalIF":3.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144817331","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":"METTL3/IGF2BP2 stabilizes IQGAP3 via m6A modification to drive HCC metastasis through TGF-β/Smad signaling and EMT","authors":"Debiao Pan ,&nbsp;Haiyuan Zhang ,&nbsp;Junbin Zhou ,&nbsp;Songqing He ,&nbsp;Guandou Yuan","doi":"10.1016/j.prp.2025.156228","DOIUrl":"10.1016/j.prp.2025.156228","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) metastasis is a leading cause of mortality, yet its molecular drivers remain poorly defined. In this study, we identify methyltransferase-like 3 (METTL3), an N6-methyladenosine (m6A) RNA methyltransferase frequently upregulated in HCC, as a critical promoter of metastasis through m6A-mediated post-transcriptional upregulation of the oncogenic protein IQ motif-containing GTPase-activating protein 3 (IQGAP3). Using HCC cell lines in vitro and a nude mouse lung metastasis model in vivo, we demonstrate that METTL3-catalyzed m6A modification of IQGAP3 mRNA enhances IQGAP3 stability and expression, which in turn drives HCC cell migration, invasion, and lung colonization. METTL3 knockdown reduces m6A marks on IQGAP3 transcripts and decreases IQGAP3 levels and metastatic capacity, whereas ectopic IQGAP3 expression rescues the invasive phenotype. Mechanistically, RNA immunoprecipitation assays reveal that Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), an m6A reader protein, binds m6A-modified IQGAP3 transcripts to prolong their half-life. Consequently, the METTL3-IQGAP3 axis activates TGF-β/Smad signaling and drives an epithelial-mesenchymal transition, thereby promoting a metastatic phenotype. Concordantly, METTL3 depletion or IGF2BP2 knockdown significantly suppresses these pathways and impedes metastasis in vitro and in vivo. Overall, our findings uncover a novel m6A-dependent mechanism driving HCC metastasis. This m6A-dependent METTL3-IGF2BP2-IQGAP3 axis represents a promising therapeutic target for metastatic HCC.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"275 ","pages":"Article 156228"},"PeriodicalIF":3.2,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145044820","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":"Mechanistic signaling pathways of flavonoid-induced oral squamous cell carcinoma therapy: Clinical evidence and therapeutic application","authors":"Md. Zamshed Alam Begh ,&nbsp;Mehrukh Zehravi ,&nbsp;Jeetendra Kumar Gupta ,&nbsp;P. Balaji ,&nbsp;Ramana Gangireddy ,&nbsp;Venkata Ramana Singamaneni ,&nbsp;Patibandla Jahnavi ,&nbsp;Aditya Kumar ,&nbsp;I. Somasundaram ,&nbsp;Rajeshwar Vodeti ,&nbsp;Prem Shankar Gupta ,&nbsp;Rajasekhar Sreerama ,&nbsp;Abdullah D. Alotaibi ,&nbsp;Safia Obaidur Rab ,&nbsp;Talha Bin Emran","doi":"10.1016/j.prp.2025.156227","DOIUrl":"10.1016/j.prp.2025.156227","url":null,"abstract":"<div><div>Flavonoids, a class of plant-derived polyphenolic chemicals, are being explored as potential candidates for oral squamous cell carcinoma (OSCC) therapy due to their anti-cancer properties. The review explores flavonoids' potential therapeutic applications and their impact on OSCC, evaluating clinical evidence and investigating flavonoid-induced therapy mechanisms. Recent research focusing on experimental and clinical investigations has been thoroughly analyzed to understand the flavonoid mechanisms of action in OSCC. The review also evaluated the efficacy and safety of flavonoid therapy in treating angiogenesis, invasion, apoptosis, and cell proliferation through clinical trials and case studies. Flavonoids exhibit anti-cancer actions in OSCC by modulating essential cell growth and survival signaling pathways like PI3K/Akt, MAPK, and NF-κB. Furthermore, the study suggests that targeting matrix metalloproteinases and other factors can prevent cancer cell invasion and metastasis and induce apoptosis through intrinsic and extrinsic pathways. Flavonoids are promising therapies for treating OSCC due to their diverse modes of action, safety profile, and ability to impact critical cancer pathways. They can reduce side effects and improve patient outcomes. However, clinical trials reveal varied outcomes, necessitating further research to enhance patient selection, dosage, and formulation. Further mechanistic studies and clinical trials are needed to enhance their therapeutic efficacy.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"275 ","pages":"Article 156227"},"PeriodicalIF":3.2,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145044818","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":"METTL3 promotes ovarian cancer progression through YTHDF2-dependent degradation of GATA4","authors":"Di Zhao ,&nbsp;Mengya Li ,&nbsp;Peiling Li","doi":"10.1016/j.prp.2025.156224","DOIUrl":"10.1016/j.prp.2025.156224","url":null,"abstract":"<div><div>Ovarian cancer (OC) remains a highly lethal gynecological malignancy with limited therapeutic options due to its aggressive progression and therapeutic resistance. N6-methyladenosine (m6A) RNA modification has emerged as a critical regulator of tumorigenesis, but the specific mechanisms linking m6A regulators to OC progression require further clarification. Here, we report that METTL3 promotes OC progression by enhancing YTHDF2-dependent degradation of the tumor suppressor GATA4. Mechanistically, METTL3-mediated hypermethylation of GATA4 transcripts at nucleotides 1837 and 2432 promotes YTHDF2-dependent mRNA decay, thereby suppressing GATA4 expression. Pharmacological inhibition of METTL3 with STM2457 increases GATA4 abundance, and attenuates malignant phenotypes of OC. Single-cell RNA sequencing (scRNA-seq) revealed that GATA4 was markedly downregulated in granulosa cells, fibroblasts, and endothelial cells within the OC microenvironment, potentially linking its loss to aberrant epithelial-mesenchymal transition (EMT), abnormal proliferation, and stromal remodeling. In conclusion, our findings establish a METTL3-YTHDF2 regulatory axis that destabilizes GATA4 mRNA, providing novel insights into the epigenetic control of OC progression. Thus, targeting this axis may offer promising therapeutic strategies to improve outcomes for OC patients.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"275 ","pages":"Article 156224"},"PeriodicalIF":3.2,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145044822","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":"Pancreatic panniculitis associated with presumed advanced pancreatic tumor: A case report and literature review","authors":"Dunya Yang ,&nbsp;Shouyue Chen ,&nbsp;Xiaoyu Zhang ,&nbsp;Xiangwu Lin ,&nbsp;Shaoqin Lin ,&nbsp;Qunxiang Chen ,&nbsp;Zongjing Zhang ,&nbsp;Jie Li ,&nbsp;Xi Chen","doi":"10.1016/j.prp.2025.156214","DOIUrl":"10.1016/j.prp.2025.156214","url":null,"abstract":"<div><div>Pancreatic tumor-associated panniculitis is a rare paraneoplastic syndrome, primarily caused by systemic release of pancreatic enzymes (e.g., lipase) from malignancies like acinar cell carcinoma (ACC), leading to necrotizing inflammation in subcutaneous and other adipose tissues. This report details an 87-year-old female presenting with progressive skin lesions (erythematous rash → indurated swelling → ulceration with purulent drainage), lower limb pain, fever, and markedly elevated lipase (3686.2 U/L). Skin biopsy confirmed lobular panniculitis with characteristic \"ghost cells\". Imaging revealed a pancreatic tail mass and liver lesions. Despite sequential anti-infectives, glucocorticoids, Octreotide, Somatostatin, Ulinastatin, and Cimetidine, her condition deteriorated, culminating in death. Literature review confirms that ACC is the predominant pancreatic tumor type causing panniculitis (accounting for 85 %). Diagnosis hinges on recognizing \"ghost cells\" pathologically and significant hyperlipasemia (often &gt;4000 U/L). Crucially, skin manifestations frequently precede abdominal symptoms, leading to misdiagnosis and delayed cancer management. Controlling panniculitis fundamentally requires treating the primary tumor: surgical resection (including metastases) significantly improves survival; platinum-based chemotherapy (e.g., FOLFOX/FOLFIRINOX) is preferred for ACC; and molecular profiling (BRCA/RAF/NTRK) guided targeted therapy is promising. Prognosis is poor; early recognition via clinician vigilance for unexplained panniculitis and pathologist identification of \"ghost cells\", coupled with multidisciplinary collaboration and aggressive tumor-directed therapy, is essential for improving outcomes.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"275 ","pages":"Article 156214"},"PeriodicalIF":3.2,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145044823","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":"Integrin β5-positive cancer-associated fibroblasts promoting lung adenocarcinoma invasion leading to poor prognosis","authors":"Saori Shibata ,&nbsp;Chihiro Inoue ,&nbsp;Yasuhiro Miki ,&nbsp;Hirotsugu Notsuda ,&nbsp;Hiromichi Niikawa ,&nbsp;Yoshinori Okada ,&nbsp;Takashi Suzuki","doi":"10.1016/j.prp.2025.156215","DOIUrl":"10.1016/j.prp.2025.156215","url":null,"abstract":"<div><div>Cancer-associated fibroblasts (CAFs) are key components of the tumor microenvironment that interact with tumor cells to promote cancer progression, including lung adenocarcinoma (LUAD). Cell adhesion molecules such as integrins play a crucial role in these interactions; however, the clinicopathological significance of integrin expression in LUAD-associated CAFs remains unclear. Hence, we evaluated the expression of integrins α2, α11, β1, and β5, which have been implicated in the progression of other cancer types, in LUAD specimens from 138 patients using immunohistochemistry. Patients with integrin α2-positive CAFs exhibited fewer adverse pathological prognostic factors. Conversely, integrin α11-, β1-, and β5-positive groups demonstrated poor pathological prognostic factors. Notably, the integrin β5-positive group had larger tumor size, higher recurrence rates, and poorer disease-free survival rates. Integrin β5 expression in CAFs was higher than that in normal fibroblasts <em>in vitro</em>. Knockdown of integrin β5 by siRNA transfection suppressed the invasion of co-cultured adenocarcinoma cells. Results from the cytokine antibody array suggest that monocyte chemoattractant protein-1 (MCP-1) and tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) enhance invasion. Inhibition of the MAPK pathway also suppressed adenocarcinoma cell invasion by reducing soluble factors, including MCP-1 and TIMP-1. These findings demonstrate that integrin β5 in CAFs promotes lung adenocarcinoma invasion, leading to poor prognosis. Therefore, targeting integrin β5 in CAFs may improve LUAD outcomes.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"275 ","pages":"Article 156215"},"PeriodicalIF":3.2,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145027178","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}