Current molecular medicine最新文献

{"title":"The Mutational Landscape of Angiosarcoma: Challenges and Opportunities to Design Management Strategies.","authors":"Swaroop Kumar Pandey, Shubhang Arya, Anuja Mishra","doi":"10.2174/0115665240410323260312134205","DOIUrl":"https://doi.org/10.2174/0115665240410323260312134205","url":null,"abstract":"<p><p>Angiosarcoma is a rare, highly aggressive endothelial malignancy comprising less than 1% of soft tissue sarcomas, with a 5-year overall survival of only 41-43%. Despite advances in cancer therapeutics, angiosarcoma remains critically understudied due to limited case prevalence, perpetuating a knowledge gap in molecular mechanisms and therapeutic strategies. Recent clinical trials (Axi-STS, TAPPAS) demonstrated that single-agent anti-angiogenic inhibitors (axitinib, pazopanib) achieve modest efficacy (median progression-free survival (PFS) 3.0-4.3 months, response rates 5-13%), underscoring angiosarcoma's complex, multipathway-driven pathogenesis. This review synthesizes the mutational landscape and molecular crosstalk of angiosarcoma, emphasizing four key mechanisms - (1) genepathway interactions-MYC amplification (>95% in radiation-associated angiosarcoma (RAAS)), TP53 mutations, and PIK3CA alterations converging to drive aggressive angiogenesis; (2) endothelial-specific dysregulation-TP53-driven disruption of VEcadherin junctions, VEGF-induced vascular permeability, and endothelial-tomesenchymal transition; (3) microenvironmental contributions- Transforming Growth Factor-Beta (TGF-β), IL-10, and VEGF-mediated immunosuppression and tumor progression; and (4) emerging biomarker-driven combinations-dual Vascular Endothelial Growth Factor (VEGF) + endoglin inhibition, chemotherapy + anti-PD-L1 immunotherapy, and multi-targeted TKI + Immune Checkpoint Inhibitors (ICI) strategies showing improved outcomes. Environmental exposures (vinyl chloride, thorotrast, radiation) drive distinct angiosarcoma subtypes with subtype-specific mutational profiles. We propose that precision-medicine approaches integrating molecular stratification, pathway crosstalk analysis, and biomarker-guided combination therapies represent the rational next steps to overcome therapeutic resistance and improve clinical outcomes in this lethal malignancy.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148142947","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":"Screening of Inflammatory Biomarkers in Atherosclerosis Based on WGCNA Analysis and Machine Learning.","authors":"Xu Xu, Meiling Jiang, Zeyun Huang, Guofu Zhu","doi":"10.2174/0115665240458730260427102717","DOIUrl":"https://doi.org/10.2174/0115665240458730260427102717","url":null,"abstract":"<p><strong>Introduction: </strong>Inflammatory response-related signaling pathways are associated with Atherosclerosis (AS), yet the particular inflammation-related genes underpinning this process are still not fully characterized.</p><p><strong>Methods: </strong>In this study, we integrated two independent transcriptomic datasets with a manually curated inflammation-related gene collection. To identify inflammation-related genes with altered expression, we intersected inflammation-related genes (IRGs), differentially expressed genes (DEGs) between atherosclerosis (AS） and controls, and inflammation score-associated genes (ISRGs) obtained from weighted gene coexpression network analysis (WGCNA) for downstream analyses. The shared genes among these sets were designated as differentially expressed inflammation-related genes (DEIRGs). We then used the DEIRGs to assemble a protein-protein interaction (PPI) network and screen for potential hub genes. Univariate logistic regression, together with least absolute shrinkage and selection operator (LASSO) regression, was used to screen candidate inflammation-related biomarkers. Their expression was then validated by reverse transcription quantitative polymerase chain reaction (RTqPCR). On the basis of the validated biomarkers, we constructed a diagnostic model. As a final analysis, Ingenuity Pathway Analysis (IPA) was used to clarify the major signaling pathways and regulatory networks associated with these biomarkers.</p><p><strong>Results: </strong>Nineteen DEIRGs were obtained as the intersection of the IRG, DEG, and ISRG gene sets. Then, 16 critical genes were identified following PPI analysis. Next, 13 feature genes were filtered using logistic analysis, of which 11 were protective elements, and 2 were risk elements. Four biomarkers (PIK3R5, ADM, RGS16, and B7RP1) were screened by LASSO analysis and RT-qPCR. IPA showed that these inflammation-related biomarkers are mainly enriched in humoral immunity and pathogen-related signaling pathways. Meanwhile, analysis of the regulatory network indicated that STAT3 and KLF6 activated ADM expression and IFNA2 activated IFNAR1 expression.</p><p><strong>Conclusion: </strong>In this study, we identified four inflammation-related biomarkers of AS (ADM, PIK3R5, B7RP1 and RGS16) that may serve as novel indicators for the diagnosis of patients with atherosclerosis.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148143016","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":"Metabolite-Based Biomarkers for Autism Spectrum Disorder: Current Research Progress.","authors":"Hong Zhou, Wenwen Tang, Yuemei Zhang, Wenjing Shi, Yingying Ren, Jiachen Dai, Reza A Ghiladi, Jun Wang","doi":"10.2174/0115665240441998260430074030","DOIUrl":"https://doi.org/10.2174/0115665240441998260430074030","url":null,"abstract":"<p><p>Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder. Its global prevalence has risen significantly and continuously in recent years, currently affecting approximately 1 in 36 individuals in the United States, making it a major worldwide public health concern. The etiology of ASD is complex, involving genetic, environmental, and interactive factors. Within this multifactorial framework, dysregulation of metabolic pathways is increasingly recognized as a pivotal driver in ASD pathogenesis. Although previous investigations have primarily focused on metabolite abnormalities within isolated pathways or specific biospecimens (e.g., blood, urine), the collective evidence remains fragmented, lacking a systematic and integrative characterization of metabolic disturbances in ASD. To address this gap, this review aims to systematically synthesize and evaluate metabolic biomarkers associated with ASD. We categorize these biomarkers according to their core pathobiological functions into five interrelated mechanistic domains for detailed discussion: neurotransmitter dysfunction, immune dysregulation, mitochondrial dysfunction, oxidative stress, and gut microbiota dysbiosis. By integrating the current evidence, we not only delineate characteristic metabolite alterations within each domain but also explore the potential cross-talk between these pathways. The identification of candidate biomarkers for early detection and to inform future strategic directions for the development of ASD interventions.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148142941","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":"Integrated Histopathological and Molecular Classification of Breast Cancer Using Immunohistochemistry (ER, PR, HER2) and KI-67.","authors":"Farah Fatima Abbas, Saba Kamil, Nehad Khan, Ruqaiya Shahid, Noor Kamil, Muhammad Ghazi Haider, Raahim Ali","doi":"10.2174/0115665240451765260424052126","DOIUrl":"https://doi.org/10.2174/0115665240451765260424052126","url":null,"abstract":"<p><strong>Introduction: </strong>Molecular classification of breast cancer based on Estrogen Receptor (ER), Progesterone Receptor (PR), and Human Epidermal growth factor Receptor-2 (HER2) expression has improved therapeutic decision-making; however, accurate differentiation between luminal subtypes remains challenging. The Ki-67 proliferation index is a valuable biomarker for assessing tumor aggressiveness and guiding treatment strategies. This study aimed to determine the frequency of molecular subtypes in breast cancer biopsies and evaluate their association with clinicopathologic parameters.</p><p><strong>Methodology: </strong>A cross-sectional study was conducted at the Histopathology Section of the Dow Diagnostic Research and Referral Laboratory (DDRRL), Dow University of Health Sciences (DUHS), Karachi, from January to December 2024. A total of 913 breast cancer biopsy specimens were analyzed using immunohistochemistry for ER, PR, HER2, and Ki-67. Tumors were classified into Luminal A, Luminal B, HER2- enriched, and Triple-Negative Breast Cancer (TNBC). Ethical approval was obtained from the DUHS Institutional Review Board (IRB-3423/DUHS/Approval/2024/93).</p><p><strong>Results: </strong>Among 913 patients, middle-aged adults [41-60 years] were most commonly affected. Luminal A [41%] was the predominant subtype, and invasive ductal carcinoma was the most frequent histological pattern. Molecular subtypes showed significant associations with tumor grade, histology, and laterality, with TNBC exhibiting a higher frequency of Grade III tumors.</p><p><strong>Discussion: </strong>Luminal A tumors were predominantly Grade II and hormone receptor- positive, whereas TNBC demonstrated higher grades and aggressive behavior. An inverse relationship between ER/PR and HER2 expression was observed. High Ki-67 index correlated with higher tumor grade and ER/PR negativity.</p><p><strong>Conclusion: </strong>Combined histopathological and molecular classification provides important prognostic information and supports individualized breast cancer management.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147980657","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":"Effect of Renal Artery Stenosis on Hind Limb Perfusion and Arteriogenesis After Left Femoral Artery Ligation in Rats: E-RASHEF Study.","authors":"Bin Zheng","doi":"10.2174/0115665240462936260429182901","DOIUrl":"https://doi.org/10.2174/0115665240462936260429182901","url":null,"abstract":"<p><strong>Background/objective: </strong>Patients with renal artery stenosis (RAS) exhibit increased risk of cardiovascular death and all-cause death. Our previous finding showed that the presence of RAS is associated with poor coronary collateral development and adverse 5-year outcome. Impaired arteriogenesis might partly explain the poor prognosis in RAS patients. This study aimed to investigate the impact of RAS on arteriogenesis and explore the possible role of interleukin-6 in this pathophysiological process.</p><p><strong>Methods: </strong>SHR rat was used as a control, while WKY rat underwent left renal artery coarctation to establish a two-kidney one-clip model with a 0.25mm silver clip at the left renal artery. Seven days after the left renal artery coarctation or sham operation, hind limb ischemia was induced by ligation of the left femoral artery. Blood pressure and heart rate were recorded every week. Laser Doppler perfusion imaging was performed at baseline, immediately after femoral ligation, at 14 and 28 days postfemoral artery ligation. Serum and hind limb tissue were collected for later analysis.</p><p><strong>Results: </strong>At the end of this study, no significant difference in blood pressure or heart rate was found between SHR and RAS rats. However, when treated with tocilizumab (TCZ), blood pressure was significantly lowered in RAS rats. Twenty-eight days after left femoral artery ligation, left hind limb perfusion was significantly worse in RAS rats than in SHR, and angiogenesis in the soleus muscle was similar between the groups, suggesting impaired arteriogenesis in RAS rats compared to SHR. Although the number of adductor muscle arterioles in RAS rats was not less than that of SHR, the mean inner diameter of arterioles in RAS rats was smaller than that of SHR. When treated with the TCZ, left hind limb perfusion in the RAS+TCZ rat was not improved. TCZ lowered serum and tissue levels of IL-6 in RAS+TCZ rats. Serum creatinine was mildly elevated in the RAS group.</p><p><strong>Discussion: </strong>Since blood pressure was similar between SHR and RAS rats, and TCZ failed to improve arteriogenesis in the RAS+TCZ group, we think that IL-6 might not be the primary mediator leading to impaired arteriogenesis in RAS rats. It seems that renal dysfunction induced by renal ischemia might have more chance to impair collateral development than hypertension or IL-6 in RAS rats.</p><p><strong>Conclusion: </strong>Existence of RAS is associated with worse arteriogenesis, which might explain the increased risk of cardiovascular death and all-cause death in patients with RAS. IL-6 might not be responsible for impaired arteriogenesis in RAS rats. Possible mechanisms need to be investigated further.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147980721","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":"Molecular Mechanisms of Cell Death in Multiple Sclerosis: Emerging Targets for Therapeutic Intervention.","authors":"Ryo-En Tan, Shi Hong Zhang, Anna Pick Kiong Ling, Soi Moi Chye, Shamala Salvamani, Crystale Siew Ying Lim, Hemavathy Subramaiam, Rhun Yian Koh","doi":"10.2174/0115665240447490260413212019","DOIUrl":"https://doi.org/10.2174/0115665240447490260413212019","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is an autoimmune disease that impacts the brain and spinal cord, which constitute the Central Nervous System (CNS), causing demyelination, inflammation, and neurodegeneration. It is a prevalent disease with limited biomarkers and treatment options. Emerging evidence, primarily from preclinical models like experimental autoimmune encephalomyelitis (EAE) and supported by human tissue studies, has explored the link between MS and various cell death pathways, including apoptosis, autophagy, necroptosis, ferroptosis, and pyroptosis. The involvement of these pathways in MS suggests the potential use of their associated molecules as biomarkers and the intervention in these pathways as therapeutic strategies. This review highlights the double-edged nature of apoptosis and autophagy: their inhibition or stimulation can either reduce or exacerbate MS progression. On the other hand, inhibiting necroptosis, ferroptosis, and pyroptosis may consistently reduce MS progression. More rigorous studies are needed to elucidate the complex relationship among MS, apoptosis, and autophagy. Molecules involved in necroptosis (such as RIPK1, RIPK3, and MLKL), ferroptosis (such as GPX4 and lipid peroxides), and pyroptosis (such as NLRP3, caspase-1, and gasdermin D) show promise as potential biomarkers for MS. Inhibitors targeting these pathways, including necrostatins (for necroptosis), ferrostatins and liproxstatins (for ferroptosis), and NLRP3 inhibitors (for pyroptosis), may offer new approaches for reducing disease progression. A comprehensive strategy that incorporates both reliable biomarkers and targeted treatments would significantly improve MS management in terms of diagnosis, monitoring, and treatment.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147980664","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 Role of suPAR in Kidney Injury Progression.","authors":"Hong Guo, Jincai Yang, Qiaoyun Ye, Luyi Xiang, Feifei Zhang, Jian Liu","doi":"10.2174/0115665240397764251029154046","DOIUrl":"https://doi.org/10.2174/0115665240397764251029154046","url":null,"abstract":"<p><strong>Introduction: </strong>This article provides a thorough review of how suPAR influences kidney injury. It aims to inform relevant fields, clarify the mechanisms of its effects, and ultimately enhance patient treatment outcomes and quality of life.</p><p><strong>Methods: </strong>A thorough literature review was conducted, analyzing published research articles, meta-analyses, and clinical studies investigating the structure, function, and pathophysiological roles of suPAR in various forms of kidney injury. Mechanisms were explored through evidence from in vitro studies, animal models, and human observational/clinical trials. The focus was on suPAR's involvement in key processes like inflammation, oxidative stress, apoptosis, and fibrosis within the kidney.</p><p><strong>Results: </strong>suPAR drives AKI progression by promoting inflammation (via NF-κB/NLRP3 activation), oxidative stress (via ROS generation), and apoptosis. In CKD, suPAR induces podocyte injury (via αvβ3 integrin/Rac1 signaling) and renal fibrosis. Elevated suPAR levels predict AKI incidence and CKD progression. suPAR also mediates AKIto- CKD transition.</p><p><strong>Discussion: </strong>suPAR is an important pathogenic mediator in kidney injury. In Acute Kidney Injury (AKI), suPAR drives progression via inflammation, oxidative stress, and apoptosis. In Chronic Kidney Disease (CKD), it promotes renal fibrosis. Furthermore, suPAR facilitates the transition from AKI to CKD.</p><p><strong>Conclusion: </strong>suPAR is a critical pathogenic factor and biomarker driving kidney injury progression in AKI (via inflammation/oxidative stress/apoptosis) and CKD (via fibrosis), and facilitates the AKI-to-CKD transition.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147970838","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 MAPK/ERK Signaling Pathway in Colorectal Cancer: Recent Advances and Emerging Insights.","authors":"Mehran Molavand, Amir Valizadeh, Bahman Yousefi","doi":"10.2174/0115665240449806260508011202","DOIUrl":"https://doi.org/10.2174/0115665240449806260508011202","url":null,"abstract":"<p><p>Colorectal Cancer (CRC) is the third most prevalent malignancy, with a high mortality rate. Ageing is a key risk factor connected with this colon- or rectumaffecting malignancy. Aberrant activation of oncogenic signaling pathways, such as MAPK/ERK, PI3K/AKT, and Notch, is frequently exhibited in CRC. The MAPK/ERK signaling cascade, as part of a broader cellular signaling network, plays a prominent role in orchestrating many biological processes. Stimulation of receptors implicated in this pathway by a wide spectrum of ligands leads to an upregulation in the expression of target genes by phosphorylated ERK. Cutting-edge molecular profiling has elucidated various mutational alterations within the MAPK/ERK pathway, with a noticeable focus on KRAS and BRAF mutant variants. Various facets of CRC advancement are intricately related to ERK hyperactivity. Prominent developmental phenomena attributed to this signaling cascade encompass elevated cellular proliferation, maintenance of the cancer stem-cell population, drug resistance, facilitation of angiogenesis, and increased invasive and migratory potential in CRC. Due to the profound role of ERK in the evolutionary stages of CRC, solving this problem depends on deepening our understanding of the ERK signaling pathway. In the domain of advancing CRC therapies, the design of personalized treatment plans assumes specific significance. The detection of KRAS and BRAF mutations in patients can be a predictive marker of therapy response and clinical outcome. By integrating recent insights, this article aims to review the complexities of MAPK/ERK's role in CRC progression and its notable potential in the development of more effective, targeted therapeutic approaches.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147971256","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":"ATIC Promotes LIHC Progression and Serves as an Independent Prognostic Marker: A Pan-cancer Transcriptomic Analysis.","authors":"Hui Li, Wentao Zhang, Xiaojie Zhou, Weiming Wu, Fuwen Yao, Haojie Zhong, Naiyang Zhan, JianWei Chen, Yongqiang Zhan, Xinping Yang","doi":"10.2174/0115665240438824260113042223","DOIUrl":"https://doi.org/10.2174/0115665240438824260113042223","url":null,"abstract":"<p><strong>Background: </strong>5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/ IMP cyclohydrolase(ATIC) is a 64-kDa bifunctional enzyme, 5-aminoimidazole- 4-carboxamide ribonucleotide formyltransferase (AICART) and IMP cyclohydrolase, respectively. catalyzes the last two steps of the purine ab initio biosynthetic pathway. ATIC has been implicated in cancer progression, but its pan-cancer profile and specific prognostic utility in liver hepatocellular carcinoma (LIHC) remain incompletely defined.</p><p><strong>Methods: </strong>We analyzed TCGA RNA-seq data across 33 tumor types to assess ATIC expression, diagnostic performance (ROC/AUC), and prognostic associations (OS, DSS, PFI). We correlated ATIC expression with immune infiltration, TMB, MSI, and predicted neoantigen load, and constructed a LIHC-specific prognostic nomogram integrating ATIC and clinicopathologic features. Enrichment analyses (STRING, GO/KEGG, GSEA) and pharmacogenomic correlations (GDSC, CTRP) were performed to explore mechanisms and drug sensitivities.</p><p><strong>Results: </strong>ATIC was significantly upregulated in 16 tumor types, including LIHC (p<0.001). Pan-cancer ROC analyses showed high diagnostic accuracy in several cancers (examples: CHOL AUC=1.000, LIHC AUC=0.936, LUAD AUC=0.947). High ATIC expression associated with poorer OS in ACC, HNSC, LIHC, and PAAD (eg, LIHC: HR=1.39(1.04-1.85), p=0.028). In LIHC, ATIC correlated with advanced T stage, higher grade, elevated AFP, and shorter OS. Multivariable Cox regression identified ATIC expression and pathological T stage as independent predictors; time-dependent ROC for the LIHC nomogram showed AUCs of 0.711, 0.649, and 0.653 at 1, 3, and 5 years, respectively. GSEA indicated enrichment of PI3K-AKT-mTOR, MYC targets, and cell-cycle pathways in ATIC-high LIHC. High ATIC expression correlated with predicted increased sensitivity to sorafenib, doxorubicin, cisplatin, epothilone, and mitomycin in the TCGA-LIHC cohort.</p><p><strong>Discussion: </strong>ATIC upregulation across cancers links to tumor progression, immune modulation, and prognosis (LIHC), suggesting oncogenic roles in pan-cancer contexts. TCGA multi-omics show ATIC associates with immune/molecular subtypes, MSI/TMB/neoantigens, and predicts drug sensitivity, indicating diagnostic/prognostic potential.</p><p><strong>Conclusion: </strong>ATIC is broadly upregulated across cancers and functions as an independent prognostic biomarker in LIHC. The ATIC-integrated nomogram shows modest predictive accuracy for LIHC survival. Our results implicate ATIC in oncogenic signaling (PI3K-AKT-mTOR, MYC, and cell-cycle) and suggest ATIC as a candidate biomarker to guide targeted and chemotherapeutic strategies in LIHC. Further in vitro and in vivo validation is warranted.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147971185","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":"Construction of an Extracellular Matrix-related Gene Model for Predicting Prognosis and Immune Features in Gastric Cancer.","authors":"Chengjun Xing, Hong Deng, Chengjie Yang, Bing Yang, Ying Wan, Jianguo Feng, Yajun Yu","doi":"10.2174/0115665240429901251230094544","DOIUrl":"https://doi.org/10.2174/0115665240429901251230094544","url":null,"abstract":"<p><strong>Introduction: </strong>The extracellular matrix (ECM) critically shapes the gastric cancer (GC) microenvironment and influences tumor initiation, proliferation, invasion, and angiogenesis. However, the prognostic significance of ECM-related genes in GC has not been systematically elucidated.</p><p><strong>Methods: </strong>Differentially expressed genes (DEGs) between GC and adjacent normal tissues were extracted from The Cancer Genome Atlas. ECM-related DEGs were identified and incorporated into a prognostic model using LASSO Cox regression. Risk scores were calculated for each patient, and a nomogram integrating clinical variables was developed. Model performance was assessed by receiver operating characteristic (ROC) analysis and validated in two independent external cohorts.</p><p><strong>Results: </strong>The ECM-based risk model stratified GC patients into high- and low-risk groups with significantly different overall survival. ROC analysis demonstrated strong predictive accuracy, and the nomogram showed good concordance between predicted and observed outcomes. Importantly, patients in the high-risk group exhibited elevated expression of immune checkpoint molecules.</p><p><strong>Discussion: </strong>The ECM-related prognostic model provides a novel framework for risk assessment in GC. Beyond prognostication, the model highlights an immunological link: the high-risk group demonstrated upregulation of immune checkpoints. These findings suggest the model not only predicts survival but may also identify subgroups of patients more likely to benefit from immunotherapy.</p><p><strong>Conclusion: </strong>We established and validated a robust ECM-related prognostic model and nomogram for GC. This tool provides clinically relevant prognostic information and may inform personalized treatment strategies, particularly in identifying patients who could benefit from immunotherapy.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147971219","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}