Clinical and Experimental Medicine最新文献

{"title":"B3GNT7 preserves intestinal barrier integrity: a key defense mechanism against acute pancreatitis progression.","authors":"Jia Hu, Yang Fu, Zehua Huang, Nuoming Yin, Binqiang Xu, Huizhen Huang, Mengyan Cui, Qixiang Mei, Chunlan Huang, Yue Zeng, Junjie Fan","doi":"10.1007/s10238-026-02186-4","DOIUrl":"10.1007/s10238-026-02186-4","url":null,"abstract":"<p><p>Mucin-2 (MUC2) plays a crucial role in maintaining intestinal homeostasis during acute pancreatitis (AP). We aimed to investigate the role of B3GNT7 (β-1,3-N-acetylglucosamine transferase) in the O-glycosylation of MUC2 in AP. We used two mouse models of AP induced by caerulein/lipopolysaccharide or L-arginine, and observed colonic goblet cells using electron microscopy, noting that Golgi damage was linked to decreased levels of mature MUC2. Golgi stress-associated proteins (reduced GM130 and elevated GOLPH3) were identified using immunofluorescence. Transcriptome analysis revealed the downregulation of B3gnt7, a glycosyltransferase that is highly enriched in the Golgi apparatus of goblet cells in AP mice. B3GNT7 expression was negatively correlated with pancreatic and colonic pathological scores. In patients with AP, intestinal B3GNT7 levels are markedly reduced and correlated with Ranson scores, C-reactive protein levels, and intestinal permeability markers (serum diamine oxidase and D-lactate). Adeno-associated virus (AAV)-mediated knockdown of B3GNT7 reduced O-glycosylated MUC2 levels, exacerbated pancreatic and systemic inflammation, and worsened intestinal permeability and dysbiosis. In vitro, LPS-treated HT-29 cells exhibited Golgi stress (decreased levels of B3GNT7 and O-glycosylated MUC2) that was reversed by L-glutathione (GSH). These findings demonstrate that B3GNT7 downregulation, mediated by Golgi stress, disrupts MUC2 O-glycosylation, exacerbating AP by impairing intestinal homeostasis.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13433732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148101206","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":"Morpho-functional plasticity of tumour-associated macrophages: linking cell shape, ultrastructure, and immune regulation in cancer.","authors":"Keerthana Suresh Kizhakkanoodan, Vidhula Jessica Inigo, Sindhura Lakshmi Koulmane Laxminarayana, Raviraja N Seetharam, Kanive Parashiva Guruprasad, Bharath Raja Guru","doi":"10.1007/s10238-026-02190-8","DOIUrl":"10.1007/s10238-026-02190-8","url":null,"abstract":"<p><p>Macrophages are highly adaptable immune cells that play dual roles in the tumor microenvironment (TME), either promoting or restraining tumor progression. Their polarization into M1 and M2 tumor-associated macrophage (TAM) phenotypes is classically defined by molecular and biochemical cues. Recent evidence shows that morphology also significantly influences the macrophage function and behavior. This review highlights the correlation between macrophage shape and function, and how cytoskeletal remodeling, extracellular matrix (ECM) stiffness, and topographical patterning regulate macrophage polarization under in vitro and in vivo conditions. We further discuss the ultrastructural features of distinct phenotypes and their mechanistic links to tumor growth and metastasis. Therapeutic strategies that target morphology through ECM modulation, engineered biomaterials, and nanoparticle platforms are examined alongside modern imaging and machine learning tools that enable precise morphometric analysis. Finally, we address the translational progress and limitations of current 2D versus 3D model systems. Overall, this review emphasizes macrophage morphology as a critical yet underexplored determinant of immune function and tumor dynamics.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13433472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148136771","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":"Exosomal integrin αvβ3 derived from colorectal cancer promotes the liver pre-metastatic niche formation by inducing cancer-associated fibroblasts activation.","authors":"Jing Yu, Jiangning Xiang, Lin Yao, Shan Wang, Yifan Liu, Enli Chen, Xiaolin Liu, JinXiang Wu, Yuhao Wang, Lei Zhao","doi":"10.1007/s10238-026-02193-5","DOIUrl":"10.1007/s10238-026-02193-5","url":null,"abstract":"<p><p>The formation of the liver pre-metastatic niche (PMN) is a critical factor in the development of colorectal cancer liver metastasis (CRLM), so understanding the mechanism of the liver PMN is crucial for the prevention and treatment of CRLM. Hepatic stellate cells (HSCs) can promote CRLM by forming cancer-associated fibroblasts (CAFs), but the mechanism remains unclear. In this study, we found that integrin αvβ3 is associated with CRLM and the poor clinical prognosis. Exosomal integrin αvβ3 derived from CRC can target HSCs via fibronectin to mediate their activation. We further explored the mechanism and found that exosomal integrin αvβ3 activates the MEK-ERK signaling pathway through the vitronectin-Integrin αvβ3-FAK axis, thereby promoting HSCs activation. After HSCs become CAFs, they promote the formation of the PMN through EMT, angiogenesis, and inflammatory factors, thereby promoting CRLM. In summary, this study clarifies that exosomal integrin αvβ3 derived from CRC can promote the formation of liver PMN by mediating HSC activation into CAFs, providing a novel therapeutic strategy for the prevention and treatment of CRLM.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13433584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148136768","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":"Current advances in immunotherapy for KRAS-Mutant pancreatic cancer.","authors":"Man Li, Xiao Wang, Pengen Li, Hongjie Gong, Jianbing Wu, Ye Mao","doi":"10.1007/s10238-026-02201-8","DOIUrl":"10.1007/s10238-026-02201-8","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive gastrointestinal cancers, with over 90% of cases harboring KRAS gene mutations. These mutations not only serve as key drivers of tumorigenesis but also reshape the tumor microenvironment (TME), creating a highly immunosuppressive \"cold tumor\" characterized by immune cell dysfunction, a dense fibrotic stroma, and a unique metabolic state. This immunosuppressive TME contributes to the widespread resistance of PDAC to immune therapies, such as immune checkpoint inhibitors (ICIs). This review systematically elucidates the mechanisms by which KRAS mutations shape the immune-suppressive TME, with a focus on the multimodal combination strategies developed to overcome this resistance. These strategies include combinations of ICIs with chemotherapy, radiotherapy, and targeted therapies (e.g., KRAS G12C/D inhibitors, PARP inhibitors, FAK inhibitors, MEK inhibitors), as well as explorations of novel immunotherapies like CAR-T cell therapy, oncolytic viruses, and T-cell agonists. Additionally, we discuss the potential of innovative localized drug delivery technologies, such as hydrogels, intelligent nanoparticle carriers, and oral spore systems, in enhancing intratumoral drug concentrations while reducing systemic toxicity. Despite the limited efficacy of monotherapy in immune treatment, increasing preclinical and clinical evidence suggests that well-designed combination strategies, by remodeling the TME through multiple targets, hold the promise of converting \"cold tumors\" into \"hot tumors,\" thereby restoring anti-tumor immune responses. Future breakthroughs in therapy will depend on the use of multi-omic biomarkers, including ctDNA, exosomes, and microbiomes, for precise patient stratification, guiding tailored immune combination therapies, and ultimately improving the survival outcomes of PDAC patients.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13433729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148101144","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":"Exosomal lncRNAs as molecular switches driving macrophage-tumor co-evolution in breast cancer.","authors":"Mahsa Javadian, Tahereh Zeinali, Morteza Rajabi, Zahra Mehrasa, Mahsa Boogari, Faezeh Ramezani, Saeed Samaeinasab, Zahra Mahmoudi, Hossein Hakimi, Rozhina Sabzehban, Khadijeh Najafi, Kiana Esmaeili, Zohreh Khaksarhaghani, Safa Tahmasebi, Ramazan Rezaei","doi":"10.1007/s10238-026-02199-z","DOIUrl":"10.1007/s10238-026-02199-z","url":null,"abstract":"<p><p>Breast cancer progression is increasingly recognized as a dynamic process shaped by reciprocal communication between malignant cells and the tumor microenvironment (TME). Among immune-cell populations, tumor-associated macrophages (TAMs) are major regulators of immune suppression, metabolic adaptation, angiogenesis, and therapeutic resistance. Emerging evidence indicates that extracellular vesicle (EV)-mediated transfer of long non-coding RNAs (lncRNAs) constitutes an important mechanism underlying tumor-immune communication in breast cancer. In this review, we summarize mechanistically characterized studies examining how exosomal lncRNAs regulate bidirectional signaling between breast cancer cells and macrophages and contribute to tumor progression, immune remodeling, and resistance-associated phenotypes. Tumor-derived exosomal lncRNAs modulate macrophage signaling through pathways associated with signal transducer and activator of transcription 3 (STAT3), transforming growth factor beta (TGF-β), Hippo/Yes-associated protein (YAP), hypoxia-responsive signaling, and autophagy-related remodeling, thereby promoting immunoregulatory and tumor-supportive macrophage phenotypes. Conversely, macrophage-derived exosomal lncRNAs, including hypoxia-inducible factor-1 alpha (HIF-1α)-stabilizing long non-coding RNA (HISLA), reinforce glycolytic adaptation, epithelial-mesenchymal transition, epigenetic remodeling, metastatic plasticity, and resistance to therapy in recipient tumor cells. Exosomal lncRNA signaling additionally influences γδ T cells, endothelial cells, and stromal compartments, supporting broader multicellular regulation within the TME. Collectively, current evidence supports exosomal lncRNAs as biologically important mediators of tumor-immune adaptation in breast cancer. We further discuss the translational potential of circulating exosomal lncRNAs as minimally invasive biomarkers and evaluate therapeutic strategies targeting EV biogenesis, vesicle trafficking, and oncogenic lncRNA cargo molecules. Finally, we highlight current limitations involving EV heterogeneity, lncRNA stoichiometry, and incomplete in vivo validation that remain critical barriers to clinical translation.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13433495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148101232","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":"Outcomes of allogeneic hematopoietic stem cell transplantation in patients with blast phase myelofibrosis: molecular signature and intensive chemotherapy matter.","authors":"Francesca Valsecchi, Maria Chiara Finazzi, Silvia Salmoiraghi, Chiara Pavoni, Anna Grassi, Alessandra Algarotti, Marta Bellini, Marco Frigeni, Annalisa Condorelli, Benedetta Rambaldi, Giuliana Rizzuto, Gianluca Cavallaro, Clara Belotti, Martina Milani, Orietta Spinelli, Federico Lussana, Alessandro Rambaldi","doi":"10.1007/s10238-026-02191-7","DOIUrl":"10.1007/s10238-026-02191-7","url":null,"abstract":"<p><p>Patients with blast-phase (BP) myeloproliferative neoplasms have dismal outcomes, but allogeneic hematopoietic stem cell transplantation (alloHSCT) may offer a potential cure. However, the optimal pre-transplant blast-reduction therapy remains to be determined. We retrospectively analyzed outcomes in a molecularly annotated cohort of 24 patients with BP myelofibrosis (MF) who underwent alloHSCT between 2008 and 2023. Before conditioning, 20 patients received intensive induction chemotherapy, 1 received decitabine plus venetoclax, and 3 proceeded directly to transplant. At transplantation, 13 patients (54%) were in complete remission (CR), defined as bone marrow blast < 5%, or CR with incomplete count recovery (CRi), while 11 (46%) had active disease. The median follow-up was 2.9 years (range 0.02-15.5). The 3-year overall survival (OS) was 62%, progression-free survival (PFS) was 49%, relapse incidence was 38%, and non-relapse mortality was 12%. There was a trend toward better OS and PFS in patients transplanted in CR/CRi compared with those with active disease (OS 68% vs. 55%, HR 0.42, p = 0.16; PFS 61% vs. 36%, HR 0.49, p = 0.21). Mutations in TP53 and EZH2 were associated with significantly inferior PFS (HR 6.28, p = 0.008 for TP53 and HR 3.8, p = 0.04 for EZH2).Compared with a historical cohort of 50 patients transplanted during the same period for chronic-phase MF, outcomes were similar (3-year OS: 62% vs. 58%; p = 0.6181). In conclusion, our results suggest that achieving remission before alloHSCT in BP-MF is associated with favorable outcomes. The adverse impact of TP53 or EZH2 mutations supports early post-transplant strategies to prevent relapse.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13433492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148101234","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":"The diagnostic and short-term prognostic significance of miR-183-5p in pulmonary embolism and its regulation of disease progression through PDCD4.","authors":"Shu Wang, Qian Wu, Wenfei Xu, Yue Wu","doi":"10.1007/s10238-026-02189-1","DOIUrl":"10.1007/s10238-026-02189-1","url":null,"abstract":"<p><p>The incidence of pulmonary thromboembolism (PTE) has increased year on year, with high rates of misdiagnosis and recurrence, as well as significant heterogeneity in prognosis. This study investigated the clinical value of miR-183-5p in PTE, as well as its mechanism of regulating disease progression through PDCD4. This study enrolled 126 PTE patients and 103 non-PTE patients. Serum miR-183-5p was detected using qPCR, and its diagnostic and prognostic significance were analyzed using ROC and logistic analyses. A PTE cell model was established using 150 µg/mL ox-LDL. The effects of inhibiting only miR-183-5p, and co-inhibiting with PDCD4, on the HPMECs functions, inflammation/oxidative stress, and adhesion molecules were analyzed. Serum miR-183-5p in PTE patients increased gradually with risk stratification. The diagnostic efficacy of miR-183-5p for PTE was superior to that of D-dimer, and combining the two provides even better diagnostic results. miR-183-5p was an independent risk factor for prognosis in PTE patients. In a PTE cell model, inhibiting miR-183-5p restored HPMECs proliferation and suppressed apoptosis and autophagy. It also reduced the inflammatory factors release, alleviated oxidative stress damage and down-regulated the adhesion molecules expression. There was a direct target relationship between miR-183-5p and PDCD4. Co-suppression both miR-183-5p and PDCD4 reversed the hindering effect of inhibiting only miR-183-5p on PTE progression. miR-183-5p is a novel biomarker for the supplementary diagnosis and 30-day short-term prognosis assessment of PTE, and it participates in PTE progression by targeting PDCD4 to regulate vascular endothelial cell function.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13407484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148041332","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":"Acute myeloid leukemia in HIV-positive patients: biological crossroads and therapeutic Hurdles.","authors":"Mohamed J Saadh, Faris Anad Muhammad, Rafid Jihad Albadr, Vimal Arora, Subbulakshmi Ganesan, Aman Shankhyan, Ajay Sharma, Jasur Rizaev, Waam Mohammed Taher, Mariem Alwan, Mahmood Jasem Jawad, Ali M Ali Al-Nuaimi","doi":"10.1007/s10238-026-02171-x","DOIUrl":"10.1007/s10238-026-02171-x","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML), characterized by aberrant hematopoiesis and aggressive clinical behavior, remains a therapeutic challenge even with advances in targeted therapies and hematopoietic stem cell transplantation. In human immunodeficiency virus (HIV)-infected individuals, leukemogenesis may be accelerated through mechanisms such as chronic inflammation, oxidative stress, and bone marrow microenvironment dysregulation. Conversely, AML-associated immunosuppression can exacerbate HIV pathogenesis, increasing the risk of opportunistic infections and complicating disease management. The overlapping clinical presentations of AML and HIV, including cytopenias and recurrent infections, often obscure diagnosis and complicate treatment decisions. While intensive chemotherapy remains the mainstay of AML treatment, HIV-positive patients face unique challenges, including potential drug-drug interactions and compounded toxicities from concurrent antiretroviral therapy (ART) and chemotherapeutic regimens. This review aims to elucidate the bidirectional relationship between HIV and AML, focusing on relevant epidemiological data, underlying molecular mechanisms, and distinct clinical features. More importantly, it identifies critical knowledge gaps that must be addressed to optimize diagnostic and therapeutic approaches for the high-risk population.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13395962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148027773","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":"CDK9 and hematologic malignancies: pioneering novel therapeutic approaches.","authors":"Hanie Raufi, Pouya Zahmatkesh, Sahar Safaei, Ata Bahadori, Saeed Solali","doi":"10.1007/s10238-026-02141-3","DOIUrl":"10.1007/s10238-026-02141-3","url":null,"abstract":"<p><p>cyclin-dependent kinase 9 (CDK9) A key regulator of transcriptional elongation influences the transcription of oncogenes and anti-apoptotic proteins. Within the context of the positive transcription elongation factor b (P-TEFb) complex, CDK9 facilitates the phosphorylation of the C-terminal domain of RNA polymerase II. It also contributes to epigenetic regulation by phosphorylating histones and altering chromatin accessibility, thereby sustaining the transcription of oncogenic programs. This mechanism initiates the transcription of genes that are crucial for the proliferation and survival of cancer cells. A variety of hematological malignancies, including acute myeloid leukemia (AML), multiple myeloma (MM), and diffuse large B-cell lymphoma (DLBCL), have been associated with dysregulated CDK9 activity, which sustains oncogene expression and contributes to resistance to treatment. A notable therapeutic approach focuses on the inhibition of CDK9. This method may function as a therapeutic strategy that exploits the transcriptional addiction of malignant cells to short-lived oncogenic transcripts. By targeting a central regulator of transcriptional elongation, this approach selectively disrupts the sustained expression of survival-critical proteins such as MCL-1 and MYC, thereby exposing a therapeutic vulnerability in hematologic malignancies. Promising outcomes in preclinical and early clinical studies have been achieved by developing selective and pharmacokinetically more effective CDK9 inhibitors. Candidates for the combination of conventional chemotherapeutic drugs with other targeted therapy modalities. Research findings indicate that innovative CDK9 inhibitors and the silencing of CDK9 through siRNA may drastically change the therapeutic approach to hematological malignancies, particularly for patients facing recurrence or resistance to prior treatments. This review focuses primarily on hematologic malignancies because they exhibit pronounced transcriptional addiction to short-lived super-enhancer-driven transcripts (MYC, MCL-1), making CDK9 inhibition particularly effective. In contrast, solid tumors often display greater microenvironmental heterogeneity and compensatory pathways that limit single-agent efficacy.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13396058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148027732","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":"Integrative analysis and experimental validation of dioxin-interacting genes reveal diagnostic and prognostic biomarkers in lung adenocarcinoma.","authors":"Guofang Yin, Bo Li, Shiming Fan, Zhiguo Wang, Qilan Jiang, Fang He, Hongli Cao, Yuling Liang, Ying Luo, Feng Jiang, Xianming Fan","doi":"10.1007/s10238-026-02187-3","DOIUrl":"10.1007/s10238-026-02187-3","url":null,"abstract":"<p><p>Dioxins are persistent environmental pollutants and key components of the human exposome with established carcinogenic potential. As airborne toxicants, they link environmental pollution to lung adenocarcinoma (LUAD), yet their molecular mechanisms remain unclear. Dioxin-interacting genes were curated from toxicogenomic databases and intersected with LUAD differentially expressed genes to identify dioxin-related molecular signatures. Consensus clustering was performed to define LUAD subtypes with distinct clinical and transcriptomic characteristics. Weighted gene co-expression network analysis (WGCNA) was applied to identify key gene modules associated with dioxin exposure and tumor progression. Hub genes were further integrated into diagnostic and prognostic models using multiple machine-learning algorithms based on both tumor tissue and peripheral blood transcriptomic datasets. Genome-exposome interactions were explored through pathway enrichment and chemical-gene interaction analyses. Single-cell RNA sequencing data were used to characterize cell-type-specific expression patterns. In vitro functional assays were conducted to validate the biological roles of candidate genes. Both models demonstrated robust predictive performance across cohorts. SLC15A2 was consistently identified as a hub gene and showed predominant expression in lung epithelial cells based on single-cell RNA sequencing. Pan-cancer analyses revealed significant dysregulation of SLC15A2, with lower expression in LUAD associated with poorer survival. Functional experiments confirmed that SLC15A2 overexpression suppressed LUAD cell proliferation and invasion, supporting a tumor-suppressive role. This integrative exposome-genome analysis highlights dioxin-related transcriptomic dysregulation in LUAD and identifies SLC15A2 as a potential tumor suppressor and biomarker for precision stratification.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13391747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148027699","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}