Current medicinal chemistry最新文献

{"title":"Identify Key Genes and Construct the lncRNA-miRNA-mRNA Regulatory Networks Associated with Glioblastoma by Bioinformatics Analysis.","authors":"Dong Xingli, Ilgiz Gareev, Sergey Roumiantsev, Ozal Beylerli, Valentin Pavlov, Shiguang Zhao, Jianing Wu","doi":"10.2174/0109298673372488250530173615","DOIUrl":"https://doi.org/10.2174/0109298673372488250530173615","url":null,"abstract":"<p><strong>Introduction: </strong>Glioblastoma is the most common and aggressive brain tumor, with low survival rates and high recurrence rates. Therefore, it is crucial to understand the precise molecular mechanisms involved in the oncogenesis of glioblastoma.</p><p><strong>Material and methods: </strong>To investigate the regulatory mechanisms of long non-coding RNA (lncRNA)-microRNA (miRNA)-messenger RNA (miRNA) network related to glioblastoma, in the present study, a comprehensive analysis of the genomic landscape between glioblastoma and normal brain tissues from the Gene Expression Omnibus (GEO) dataset was first conducted to identify differentially expressed genes (DEGs) in glioblastoma. Following a series of analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, protein-protein interaction (PPI), and key model analyses. In addition, we used the L1000CDS2 database bioinformatic tool to identify candidates for therapy based on glioblastoma specific genetic profile.</p><p><strong>Results: </strong>In our results, 100 key genes, 50 upregulated and 50 downregulated, were ultimately identified. The results of KEGG pathway enrichment gene analysis showed that the five regulatory pathways. Furthermore, 3 small molecule signatures (trichostatin A, TG-101348, and vorinostat) were recommended as the top-ranked candidate therapeutic agents. Nevertheless, the constructed miRNA-mRNA network revealed a convergence on 40 miRNAs. We found that dysregulation of lncRNAs such as KCNQ1OT1 and RP11-13N13.5 could sequester several miRNAs such as hsa-miR-27a-3p, hsamiR- 27b-3p, hsa-miR-106a-5p, etc., and promote the development and progression of glioblastoma.</p><p><strong>Conclusions: </strong>Our study identified key genes and related lncRNA-miRNA-mRNA network that contribute to the oncogenesis of glioblastoma.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505072","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 the Role of DPF1 in Hepatocellular Carcinoma: Implications for Prognosis and Therapy.","authors":"Fan Yang, Yinyi Li, Dan Chen, Xiuju Wang, Mei Sun, Dongbing Li, Niansong Qian","doi":"10.2174/0109298673363347250529114300","DOIUrl":"https://doi.org/10.2174/0109298673363347250529114300","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is a life-threatening cancer with rising incidence and mortality rates. Identifying new prognostic biomarkers is crucial for improving HCC management.</p><p><strong>Objectives: </strong>This study investigates the role of Double PHD Fingers 1 (DPF1) in hepatocellular carcinoma (HCC), exploring its potential as a prognostic indicator and therapeutic target.</p><p><strong>Methods: </strong>We analyzed DPF1 expression in 374 hepatocellular carcinoma (HCC) tissues and 50 normal tissues from the TCGA-HCC database, as well as in 240 HCC tissues and 202 normal tissues from the ICGC-HCC repository. We examined the correlation between DPF1 expression and clinical parameters, immune cell infiltration, drug response profiles, cancer stem cell (CSC) characteristics, and its diagnostic/prognostic potential using various bioinformatics tools and statistical analyses. Validation was performed using the ICGC and HPA databases, and qRT-PCR was used to confirm DPF1 expression in HCC cell lines.</p><p><strong>Results: </strong>DPF1 exhibited abnormal expression in HCC and several other malignancies. Elevated DPF1 levels were significantly associated with higher Alpha-fetoprotein (AFP) levels (p = 0.043) and poorer clinical outcomes, including diminished overall survival (OS) (p = 0.002), progression-free survival (PFS) (p = 0.018), and disease-specific survival (DSS) (p = 0.001). DPF1 expression was also linked to immune cell infiltration, immune checkpoint gene expression, drug sensitivity, and CSC characteristics. Notably, DPF1 was significantly overexpressed in HCC tissues and cell lines at both transcriptional and translational levels.</p><p><strong>Conclusion: </strong>Our study reveals that DPF1 is a novel prognostic biomarker in HCC, with potential implications for immunotherapy and drug resistance. Elevated DPF1 expression is associated with adverse clinical outcomes and may serve as a target for future therapeutic interventions in HCC.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505071","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":"Research Progress of Wound Dressing Based on Sodium Alginate Composite Hydrogel.","authors":"Fengchao Zhou, Shibin Deng, Guorong Lin, Jiandong Shen, Dianping Tang","doi":"10.2174/0109298673362140250530094233","DOIUrl":"https://doi.org/10.2174/0109298673362140250530094233","url":null,"abstract":"<p><p>Hydrogel wound dressing has significant advantages in wound treatment. It can shorten the time of wound healing, control the process of wound healing, and effectively promote the healing of damaged tissues in a hydrated environment. Sodium alginate (SA) is a commonly used hydrogel wound dressing material, which can quickly form a three-dimensional network structure hydrogel in a relatively mild environment, but the mechanical properties and stability of a single SA hydrogel are poor. The composite hydrogel prepared by mixing SA with other substances can not only exert the performance of a single substance but also improve the mechanical properties, stability and adsorption of the hydrogel and has a wider application prospect in the field of sustained release control of bioactive substances. Natural polymers have been widely used in the preparation of hemostatic and wound healing materials due to their excellent biocompatibility, degradability, viscoelasticity and easy processing. This paper introduces the research progress of composite hydrogels prepared by SA and natural polymers in mechanical properties, antibacterial, anti-inflammatory, tissue repair and sustained release control of bioactive substances, and provides a theoretical basis for the application of SAbased composite hydrogels in wound dressings.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505074","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":"Paneth Cells: Recent Updates on Elucidating Therapeutic Implications in Gastroenterological Disease Management.","authors":"Maria V Sankova, Vladimir N Nikolenko, Anastasia A Bolotskaia, Marine V Oganesyan, Negoriya A Rizaeva, Aleksey V Sankov, Tatyana S Zharikova, André Pontes-Silva, Narasimha Murthy Beeraka, Hemanth Vikram P R, Padmanabha Reddy Y, Dilip Kumar Reddy Kandula, B M Gurupadayya, Yury O Zharikov","doi":"10.2174/0109298673357073250526104619","DOIUrl":"10.2174/0109298673357073250526104619","url":null,"abstract":"<p><strong>Background: </strong>The human intestine is continuously exposed to a variety of aggressive agents, including food antigens, xenobiotics, numerous pathogenic microorganisms, metabolic products, and toxins. Consequently, it has developed a specialized system for protection against these adverse factors.</p><p><strong>Objective: </strong>This study aims to investigate the biochemical compounds synthesized by Paneth cells and their mechanisms of action to develop new therapeutic approaches for gastroenterological diseases.</p><p><strong>Methods: </strong>We conducted a systematic review, excluding a comprehensive meta-analysis, of the current scientific literature sourced from electronic libraries (CyberLeninka, e-Library.ru, and Cochrane Library), search engines (Google Scholar, Embase, and Global Health), and scientific databases (Elsevier, Medline, PubMed-NCBI, and Scopus). Following PRISMA guidelines, a total of 104 articles were initially selected based on defined inclusion and exclusion criteria. After careful evaluation, 63 articles were included in this study.</p><p><strong>Results: </strong>Our findings indicate that Paneth cells play a crucial role in regulating small intestine homeostasis by secreting numerous biologically active molecules. A key feature of these cells is their ability to recognize soluble microbial products via pattern recognition receptors and respond by releasing a variety of antimicrobial peptides and enzymes. These secretions contribute to the formation of a biochemical barrier that prevents pathogen adhesion and translocation. Paneth cells are integral to immunological protection, maintaining protective inflammatory responses under both normal and pathological conditions. Additionally, they regulate the division, growth, and differentiation of intestinal stem cells, ensuring proper enterocyte localization. Paneth cells also aid digestive processes through enzyme secretion and are the only epithelial cells capable of eliminating activated autoreactive lymphocytes and abnormal enterocytes.</p><p><strong>Conclusion: </strong>Paneth cells are unique epithelial cells that, through the synthesis of numerous biologically active molecules, control the timely regeneration of the intestinal epithelium, maintain a healthy microbiota, and prevent infectious, autoimmune, and cancerous diseases. Understanding their role in these processes is crucial for developing new therapies for gastroenterological diseases.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332631","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":"Knockdown of TRIM65 Inhibits Neoangiogenesis in Proliferative Diabetic Retinopathy by Regulating miR29a-3p.","authors":"Xinxin Chen, Xiaolong Chen, Shuai Huang, Yang Xian, Ruining Han","doi":"10.2174/0109298673325802240813103408","DOIUrl":"10.2174/0109298673325802240813103408","url":null,"abstract":"<p><strong>Introduction: </strong>High glucose-induced angiogenesis is the main component in Proliferative Diabetic Retinopathy (PDR) development. In PDR, ischemia and hypoxia have been identified as key stimuli that promote pathological neoangiogenesis by increasing Vascular Endothelial Growth Factor A (VEGFA). Furthermore, it has been demonstrated that TRIM65 knockdown in tumor cells reduces VEGFA expression. Building on these findings, the present study aimed to study the role of TRIM protein members in proliferative diabetic retinopathy.</p><p><strong>Method: </strong>In comparison to the control group, TRIM65 expression was significantly increased in human retinal endothelial cells (HREC) after high glucose treatment. Moreover, FITC/PI staining, cell wound scratch assay, transwell assay, tube formation assay, and immunofluorescence staining of VEGFA and HIF-3α were carried out, which indicated that TRIM65 knockdown inhibited high glucose-induced HREC cell apoptosis and angiogenesis and decreased the expression of VEGFA and HIF-3α, both of which are potential targets of miR-29a-3p. MIR-29a-3p inhibitor significantly reduced the effects of TRIM65 knockdown on VEGFA and HIF-3α expression levels in cells. TRIM65 induced ubiquitination and degradation of TNRC6A, resulting in suppressed miR-29a-3p expression.</p><p><strong>Result: </strong>Furthermore, in vivo studies revealed that intravitreal injection of miR-29a-3p inhibited neoangiogenesis in mice with Oxygen-Induced Retinopathy (OIR). The retinal tissues of OIR mice showed higher TRIM65 mRNA expression and lower miR-29a-3p expression than those of control mice. Furthermore, the analysis showed a negative correlation between the expression of miR-29a-3p and TRIM65 in the retinal tissues of OIR mice.</p><p><strong>Conclusion: </strong>In conclusion, this study demonstrated that the knockdown of TRIM65 inhibits neoangiogenesis in proliferative diabetic retinopathy by regulating miR-29a-3p.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332630","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 Prognostic Lysine Crotonylation Signature Shapes the Immune Microenvironment in Hepatocellular Carcinoma.","authors":"Weiping Su, Kuo Kang, Xuanxuan Li, Heyuan Huang","doi":"10.2174/0109298673381518250529110617","DOIUrl":"https://doi.org/10.2174/0109298673381518250529110617","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Hepatocellular carcinoma (HCC) has a poor prognosis due to late diagnosis and rapid progression, highlighting the need for a deeper understanding of its pathogenesis. Lysine crotonylation (Kcr), a unique post-translational modification, plays a crucial role in epigenetic regulation. However, the role of crotonylation-related genes (CRGs) in HCC remains poorly understood, necessitating an investigation of their prognostic and therapeutic relevance.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Transcriptomic and clinical data were obtained from TCGA and GEO databases. A CRG-based risk score was developed using Cox and LASSO regression analyses. To enhance survival prediction, a nomogram incorporating the risk score was constructed. Immune cell infiltration and drug sensitivity were assessed using CIBERSORT and 'OncoPredict.' Single-cell sequencing was employed to examine CRG expression within the HCC tumor microenvironment.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;An 8-gene risk score model (HDAC2, ACADS, HDAC1, ENO1, PPARG, ACADL, ACSL6, and AGPAT5) was established, effectively stratifying patients into high- and low-risk groups in the training set. Cox regression and Kaplan-Meier analyses validated its prognostic value in the test set. The nomogram demonstrated enhanced prognostic accuracy for survival prediction. Differences in immune cell infiltration and immune checkpoint expression between risk groups highlighted the association between CRGs and the tumor immune microenvironment. Single-cell sequencing revealed that CRGs were highly expressed in key immune cells within the HCC microenvironment. Additionally, drug sensitivity analysis suggested that specific targeted therapies may be more effective in HCC patients.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;Crotonylation-related gene signature demonstrates strong prognostic value in hepatocellular carcinoma (HCC), effectively stratifying patients into high- and low-risk groups and recapitulating known oncogenic roles of HDAC1/2, ENO1, PPARG, AGPAT5 and the protective functions of ACADS, ACADL, and ACSL6. It was found that crotonylation not only influences tumor cell metabolism and epigenetic regulation but also shapes the immune microenvironment, highlighted by distinct checkpoint expression, differential immune cell infiltration, and drug sensitivity profiles, which positions our model as a promising tool for personalized therapeutic decision-making. However, clinical translation will require standardized, reproducible assays for crotonylation measurement and rigorous validation across diverse HCC etiologies (e.g., viral vs. non-viral), along with mechanistic and longitudinal studies to dissect causality versus correlation, assess off-- target effects of crotonylation modulators, and confirm functional impacts on immune modulation before routine diagnostic or therapeutic use.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This study identifies a prognostic CRG signature for HCC and provides novel ins","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316125","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":"Analysis of Pan-Specific Inhibitors of Oncogenic Mutant Forms of KRAS GTPase.","authors":"Ilya A Eliseev, Dmitrii O Shkil, Valentina S Shumakova, Vladimir V Chernyshov, Konstantin V Balakin, Roman A Ivanov","doi":"10.2174/0109298673372217250515031136","DOIUrl":"https://doi.org/10.2174/0109298673372217250515031136","url":null,"abstract":"<p><p>The KRAS protein is one of the key targets in cancer therapy. The clinical application of covalent KRAS inhibitors (sotorasib, adagrasib) is limited to the treatment of only certain KRASG12C-mediated types of cancer. In addition, using covalent inhibitors has several drawbacks, the main ones being limited to specific mutations (e.g., G12C) and the potential development of mutagenic resistance in tumors. Recently, the first representatives of a new class of allosteric inhibitors, termed pan-KRAS, have been discovered and studied due to their activity against multiple mutant forms of the KRAS protein. The development of pan-KRAS inhibitors represents a promising new direction in the therapeutic approach to treating KRAS-mediated cancers. The possibility to target multiple mutant forms of KRAS will significantly enlarge the number of patients that benefit from the therapy and reduce the likelihood of mutagenic resistance in tumors. This study reviews patents published between 2022 and 2024 that present new pan-specific KRAS inhibitors. The consideration of 28 patents included descriptions of the structures of the presented molecules, identification of the most active and selective examples of compounds, as well as results from structure-activity relationship (SAR) analyses for each sample. As a result of this work, some structural features of the most active examples of pan-KRAS inhibitors were identified.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316126","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 between Maternal Hypertension and Cleft Lip and Palate: A Mendelian Randomization Study.","authors":"Wenkang Luan, Shujun Fan, Haojun Liang, Dongwen Jiang, Leren He","doi":"10.2174/0109298673364806250523062350","DOIUrl":"https://doi.org/10.2174/0109298673364806250523062350","url":null,"abstract":"<p><strong>Background: </strong>There is still no consensus on the etiology and risk factors of cleft lip and palate, and the causal relationship between maternal hypertension and cleft lip and palate remains uncertain.</p><p><strong>Objective: </strong>We used two-sample Mendelian Randomization (MR) to investigate the causal effect of maternal hypertension on cleft lip and palate.</p><p><strong>Methods: </strong>The MR study was performed using the statistics from the Genome-Wide Association Studies (GWAS) of maternal hypertension and cleft lip and palate. Using 25 Single-Nucleotide Polymorphisms (SNPs) robustly associated with maternal hypertension as instrumental variables, we employed several MR approaches, including Inverse Variance Weighted (IVW), weighted median, simple mode, MR-Egger, and weighted mode. Heterogeneity and pleiotropy tests were also conducted.</p><p><strong>Results: </strong>The causal relationship between maternal hypertension and cleft lip and palate (CL/P) was identified using IVW (OR = 3.603, 95% CI = 1.184-10.964, p = 0.024). Additionally, a causal effect of maternal hypertension on cleft lip (CL) risk was identified using IVW (OR = 5.968, 95% CI = 1.023-34.819, p = 0.047). However, no significant association between maternal hypertension and Cleft Palate Only (CPO) was observed across all MR methods.</p><p><strong>Conclusion: </strong>The MR analysis indicated that maternal hypertension is causally associated with the risk of CL/P and CL.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316127","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 Circadian Rhythm-related Genes for Prognosis Modeling and Immune Characterization in Thyroid Cancer.","authors":"Xiuping Qiu, Gang Chen, Mei Tu","doi":"10.2174/0109298673374398250523073407","DOIUrl":"https://doi.org/10.2174/0109298673374398250523073407","url":null,"abstract":"<p><strong>Background: </strong>Circadian rhythm-related genes (CRRGs) play a crucial role in regulating cellular processes, including survival, invasion, proliferation, and metastasis across various tumors. However, their specific function in thyroid cancer (THCA) remains uncertain. This study explores the prognostic significance of CRRGs in THCA and evaluates their potential as therapeutic targets.</p><p><strong>Methods: </strong>Clinical and gene expression data from the Cancer Genome Atlas (TCGA) were analyzed to assess the relevance of CRRGs in THCA. Somatic mutation analysis, risk model development, and comparisons between high- and low-risk patient groups were carried out using Gene Set Variation Analysis (GSVA). Tumor immune microenvironment characteristics were evaluated, and data from Kaplan-Meier (K-M) survival analysis was used to examine prognostic outcomes. Functional validation of nine CRRGs, namely CHEK1, GHR, ID3, IDI1, MAGEL2, NLGN1, PPARGC1A, TBL1X, and TF, was conducted through in vitro experiments.</p><p><strong>Results: </strong>The CRRG-based risk model stratified patients into high- and low-risk groups, with K-M analysis revealing that patients in the low-risk group had significantly poorer outcomes. Functional analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA), identified pathways associated with THCA in both groups. Using single-sample GSEA (ssGSEA), patients were further categorized by circadian rhythm scores (CRscores), highlighting distinct immune profiles between the two groups. A clinical Cox model was developed, and differential gene expression was validated through in vitro experiments.</p><p><strong>Conclusion: </strong>This study presents a novel CRRG-based prognostic model for THCA, providing a valuable tool for patient stratification and providing insights for optimizing immunotherapy strategies.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316128","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":"Systematic Pan-Cancer Analysis of the Oncogenic and Immunological Function of Stanniocalcin-1 (STC1).","authors":"Long Zhao, Changjiang Yang, Zhidong Gao, Yingjiang Ye, Lin Gan","doi":"10.2174/0109298673358794250531003706","DOIUrl":"https://doi.org/10.2174/0109298673358794250531003706","url":null,"abstract":"<p><strong>Background: </strong>Stanniocalcin 1 (STC1) has been implicated in cancer pathogenesis, yet its pan-cancer implications and mechanistic roles in tumor progression and immune modulation remain incompletely characterized. The clinical relevance of STC1 in predicting prognosis and its interaction with tumor immune microenvironment components require systematic investigation.</p><p><strong>Objective: </strong>This study aims to establish the pan-cancer prognostic significance of STC1 and elucidate its associations with immunological characteristics, including immune checkpoint proteins, tumor mutational burden (TMB), microsatellite instability (MSI), and immune cell infiltration. We specifically focus on validating its role in gastric adenocarcinoma (STAD) pathogenesis.</p><p><strong>Methods: </strong>Multi-omics analysis was performed using TCGA pan-cancer datasets and bioinformatics tools (UALCAN, cBioPortal, HPA, GTA). Experimental validation included multiplex fluorescence staining of STAD tissue microarrays (n=30) and Western blot analysis of STAD cell lines. Key parameters analyzed encompassed clinical outcomes, cancer stemness indices, neoantigen load, and epithelial-mesenchymal transition (EMT) signatures.</p><p><strong>Results: </strong>Pan-cancer analysis revealed significant STC1 overexpression in 18/33 cancer types (54.5%), particularly in prostate adenocarcinoma (94% deep deletions). STC1 expression correlated with poor prognosis (HR=1.32, p<0.01), elevated TMB (r=0.43), and MSI (r=0.38) across multiple malignancies. Single-cell RNA sequencing demonstrated strong EMT association (NES=2.18, FDR<0.001). In STAD, we confirmed 3.7-fold protein overexpression (p=0.008) and identified positive correlations with CD8+ T cell (r=0.62, p=0.002) and CD4+ T cell infiltration (r=0.58, p=0.004).</p><p><strong>Conclusion: </strong>This multi-modal study establishes STC1 as a novel pan-oncogenic factor with dual roles in tumor progression (via EMT and stemness regulation) and immune microenvironment remodeling. The strong association with immune checkpoints (PD-L1, CTLA4) and T cell infiltration patterns positions STC1 as a promising immunotherapeutic target, particularly in STAD and MSI-high cancers. Our findings provide mechanistic insights for developing STC1-directed therapeutic strategies.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316129","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}