Biochemistry and Biophysics Reports最新文献

{"title":"Computational identification of novel natural inhibitors against triple mutant DNA gyrase A in fluoroquinolone-resistant Salmonella Typhimurium","authors":"Sree Haryini,&nbsp;George Priya Doss C","doi":"10.1016/j.bbrep.2024.101901","DOIUrl":"10.1016/j.bbrep.2024.101901","url":null,"abstract":"<div><div>The rising resistance to fluoroquinolones in <em>Salmonella</em> Typhimurium poses a significant global health challenge. This computational research addresses the pressing need for new therapeutic drugs by utilizing various computational tools to identify potential natural compounds that can inhibit the triple mutant DNA gyrase subunit A enzyme, which is crucial in fluoroquinolone resistance. Initially, the three-dimensional structure of the wild-type DNA gyrase A protein was modeled using homology modeling, and followed by <em>in silico</em> mutagenesis to create the clinically relevant triple mutant (SER83PHE, ASP87GLY, ALA119SER) DNA gyrase A protein structure. The structural stability and integrity of the modeled protein were ensured through rigorous validation. Subsequently, a high-throughput virtual screening of a curated library of natural compounds was conducted to identify potential inhibitors against wild-type and triple-mutant proteins. The selected potent lead molecules comprehensively evaluated their physicochemical properties, ADME/T properties, and binding affinities via ADME/T assessment and molecular docking studies. The safest and most promising ligands were chosen for dynamics studies to analyze their dynamic behavior and protein stability before and after the binding of ligands. Our results showed that the natural compounds from the ChemDiv database, CID: 0407–0108, N039-0003, 1080–0568, and 0099–0261 have binding energies ranging from −4.32 to −5.69 kcal/mol and exhibit excellent physio-chemical properties, affinities, and are stable in their dynamic environments over 100 ns for both wild-type and triple mutant DNA gyrase A complexes. These compounds provide a promising alternative treatment for fluoroquinolone-resistant <em>Salmonella</em> Typhimurium infections.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"41 ","pages":"Article 101901"},"PeriodicalIF":2.3,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11764029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dopamine receptors and organ fibrosis","authors":"ZhongLi Liao ,&nbsp;XueFeng Tang ,&nbsp;Bin Yang ,&nbsp;Jian Yang","doi":"10.1016/j.bbrep.2024.101910","DOIUrl":"10.1016/j.bbrep.2024.101910","url":null,"abstract":"<div><div>Organ fibrosis, considered as a major global health concern, is a pathological condition often occurring after tissue injury in various organs. The pathogenesis of fibrosis involves multiple phases and multiple cell types. Dopamine is involved in various life activities by activating five receptors (D1, D2, D3, D4, D5). Activation or loss of function of dopamine receptors has been reported to be associated with the fibrosis of several organs, such as ocular, lung, liver, heart, and kidney. In this paper, we review dopamine receptors’ potential roles in organ fibrosis and mechanisms by which organ fibrosis develops or decreases when dopamine receptors function is activated or perturbed.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"41 ","pages":"Article 101910"},"PeriodicalIF":2.3,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elucidating the therapeutic potential of indazole derivative bindarit against K-ras receptor: An in-silico analysis using molecular dynamics exploration","authors":"Parmar Keshri Nandan,&nbsp;Jayanthi Sivaraman","doi":"10.1016/j.bbrep.2024.101913","DOIUrl":"10.1016/j.bbrep.2024.101913","url":null,"abstract":"<div><div>Ras gene is frequently mutated in cancer. Among different subtypes of Ras gene, K-Ras mutation occurs in nearly 30 % of human cancers. K-Ras mutation, specifically K-Ras (G12D) mutation is prevalent in cancers like lung, colon and pancreatic cancer. During cancer occurrence, mutant Ras remain in activated form (GTP bound state) for cancer cell proliferation. In the quest for a potential K-Ras inhibitor, nitrogen-containing indazole derivatives can show promise as inhibitors, as they have numerous therapeutic properties like anti-inflammatory, anti-viral and anti-tumor. Furthermore, among various indazole derivatives, “Bindarit” is an important therapeutic compound which could have potential inhibitory action against K-Ras due to its structural resemblance with reference compound “Benzimidazole”. So, the current study is an attempt to find out the inhibitory effect of Bindarit against K-Ras activation by binding to a pocket which is adjacent to the switch I/II regions of the K-Ras receptor. AutoDock tool was used to investigate the binding affinity of protein ligand interaction and GROMACS package was utilised to assess their interactions in a dynamic setting. Bindarit shows better binding affinity than reference with binding energy of −7.3 kcal/mol. Upon ligand binding conformational changes take place, which could lead to the loss of GTPase activity. Consequently, further downstream signalling of the K-Ras pathway would be blocked and this could lead to the inhibition of K-Ras dependent cancer cell proliferation. However, further validation of present study can be done through experimental assay such as cytotoxic and protein expression analysis.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"41 ","pages":"Article 101913"},"PeriodicalIF":2.3,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11758134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The prognostic significance of epoxide hydrolases in colorectal cancer","authors":"Lichao Cao ,&nbsp;Ying Ba ,&nbsp;Fang Chen ,&nbsp;Dandan Li ,&nbsp;Shenrui Zhang ,&nbsp;Hezi Zhang","doi":"10.1016/j.bbrep.2024.101912","DOIUrl":"10.1016/j.bbrep.2024.101912","url":null,"abstract":"<div><div>Colorectal cancer (CRC) is a common malignant cancer. Epoxide hydrolases (EHs) are involved in the development of cancer by regulating epoxides, but their relationship with CRC is unclear. We used multiple datasets to confirm the expression of different EPHX family members in CRC tissues, and to explore their association with different clinicopathologic characteristics. The Kaplan–Meier method, correlation analysis and random forest algorithm were used to evaluate the prognostic value of EPHX family members for CRC. Finally, the cell experiment verified function of EPHX4 in CRC. The expressions of EPHX1 and EPHX2 were significantly decreased, while those of EPHX3 and EPHX4 were significantly increased in CRC. The expressions of EPHX family members were correlated with some clinicopathologic features and overall survival. The expressions of the EPHX family were positively associated with CD274, CTLA4, HAVCR2, and TIGIT. EPHX2 and EPHX4 were diagnostic and predictive biomarkers for CRC. EPHX4 promoted the malignant phenotype of CRC cells. Our study firstly elucidated the prognostic significance of EPHX family members in CRC and identified novel diagnostic and prognostic biomarkers for CRC.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"41 ","pages":"Article 101912"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring miRNA profile associated with cisplatin resistance in ovarian cancer cells","authors":"Yaman Alghamian ,&nbsp;Chadi Soukkarieh ,&nbsp;Abdulmunim Aljapawe ,&nbsp;Hossam Murad","doi":"10.1016/j.bbrep.2024.101906","DOIUrl":"10.1016/j.bbrep.2024.101906","url":null,"abstract":"<div><div>Ovarian cancer is a common and lethal malignancy among women, whereas chemoresistance is one of the major challenges to its treatment and prognosis. Chemoresistance is a multifactorial phenomenon, involving various mechanisms that collectively modify the cell's response to treatment. Among the changes that arise in cells after acquiring chemoresistance is miRNA dysregulation. Here, this study aimed to identify miRNAs expression changes related to cisplatin resistance in ovarian cancer cells. The miRNA expression profiles of a cisplatin-sensitive A2780 cell line and two cisplatin-resistant cell lines, A2780cis and SK-OV-3, were analyzed using PCR array and qPCR. Accordingly, the miRNAs that were differentially expressed were further investigated to identify their biological functions and the target pathways using Gene Ontology (GO) annotation and KEGG pathway analyses. In order to evaluate the clinical significance of the differentially expressed miRNAs, survival analysis was carried out using expression data for ovarian cancer patients available in the Kaplan-Meier (KM) plotter database. The current work demonstrates that Nine miRNAs were found to be upregulated in cells resistant to cisplatin. Clearly, these miRNAs have functions in cell death/survival related processes and treatment response. They may also target pathways involved in treatment response like PI3K-Akt, pathway in cancer and MAPK. Interestingly, High expression of hsa-miR-133b, hsa-miR-512-are, hsa-miR-200b-3p, and hsa-miR-451a is related to poor overall survival in patients diagnosed with ovarian cancer. Our findings suggest that hsa-miR-133b, hsa-miR-512-5p, hsa-miR-200b-3p, and hsa-miR-451a are good candidates for future studies aimed to establishing functional links and exploring therapeutic interventions to overcome cisplatin resistance.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"41 ","pages":"Article 101906"},"PeriodicalIF":2.3,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11741906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of β-catenin on hypoxia induced epithelial mesenchymal transition in HK-2 cells by regulating Brachyury","authors":"Ping Sun ,&nbsp;Haihui Yang ,&nbsp;Binying Min ,&nbsp;Yongfu Li ,&nbsp;Jun Wang ,&nbsp;Mo Chen ,&nbsp;Diping Yu ,&nbsp;Wenjuan Sun","doi":"10.1016/j.bbrep.2024.101907","DOIUrl":"10.1016/j.bbrep.2024.101907","url":null,"abstract":"<div><h3>Background</h3><div>Chronic kidney disease (CKD) has become a worldwide health problem and the incidence rate and mortality of CKD have been rising. Renal fibrosis (RF) is the final common pathological feature of almost all kinds of CKD and Epithelial-mesenchymal transition (EMT) is the predominant stage of RF. β-catenin is a key component of the Wnt signaling pathway, which has been fully proven to promote EMT. However, the underlying mechanism of β-catenin in EMT during the pathogenesis of RF is yet to be determined.</div></div><div><h3>Objective</h3><div>This study was designed to investigate the effects of β-catenin on RF-related EMT and further investigate its underlying mechanism.</div></div><div><h3>Methods</h3><div>Human proximal tubular epithelial cell (HK-2) was treated with hypoxia to construct RF injury cell model. The viability of cells was determined by CCK-8 assay. Immunofluorescence was used to detect α-SMA content. Expressions of β-catenin, Brachyury and RF-related proteins were measured by Western blot. The correlation between β-catenin and Brachyury was detected by ChIP-qPCR and dual luciferase reporter assay.</div></div><div><h3>Results</h3><div>We found β-catenin was overexpressed in hypoxia-induced HK-2 cells. In the RF cell model, silencing of β-catenin weakened the EMT and fibrogenesis activity of HK-2 cells. Mechanistically, we found β-catenin binds to T-cell factor (TCF) to activate Brachyury, which is a positive player in EMT. Further studies clarified that Brachyury was responsible for β-catenin-promoted the EMT and HK-2 cell injury under hypoxia condition.</div></div><div><h3>Conclusions</h3><div>Herein, we demonstrated that β-catenin is overexpressed in hypoxia-induced HK-2 cells and promotes EMT and cell injury via activating Brachyury. These findings suggest that targeting β-catenin/Brachyury may be an effective new approach for treating RF.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"41 ","pages":"Article 101907"},"PeriodicalIF":2.3,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11741901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of platelet-rich plasma on ferroptosis of nucleus pulposus cells induced by Erastin","authors":"Shi-lin Lian ,&nbsp;Jie Huang ,&nbsp;Yan Zhang ,&nbsp;Yu Ding","doi":"10.1016/j.bbrep.2024.101900","DOIUrl":"10.1016/j.bbrep.2024.101900","url":null,"abstract":"<div><h3>Background</h3><div>Intervertebral disc degeneration (IVDD) has been linked to ferroptosis, a type of programmed cell death. The role of platelet-rich plasma (PRP) in mitigating ferroptosis in nucleus pulposus (NP) cells within IVDD remains unclear.</div></div><div><h3>Purpose</h3><div>This study aims to verify the effectiveness of PRP in reducing ferroptosis in NP cells induced by Erastin.</div></div><div><h3>Methods</h3><div>Primary NP cells were isolated from SD rats, and a ferroptosis model was established using Erastin. PRP was prepared and applied to assess its impact on ferroptosis-related markers, including reactive oxygen species (ROS), iron content, and glutathione peroxidase 4 (GPX4). The effects of PRP on the ultrastructure of NP cells were also observed using transmission electron microscopy (TEM).</div></div><div><h3>Results</h3><div>PRP treatment significantly restored GPX4 levels (431.47 ± 4.70 ng/L vs. 69.70 ± 4.06 ng/L, P &lt; 0.05), reduced ROS levels (45.06 ± 3.78 vs. 155.36 ± 3.56, P &lt; 0.05), and decreased iron content (32.24 ± 096 μg/L vs. 59.25 ± 3.72 μg/L, P &lt; 0.05) in ferroptotic NP cells compared to the sham group. Additionally, PRP significantly increased the expression levels of collagen Ⅱ (0.72 ± 0.02 vs. 0.33 ± 0.02, P &lt; 0.05) and aggrecan (0.81 ± 0.01 vs. 0.31 ± 0.02, P &lt; 0.05) compared to the sham group. TEM analysis also showed improvements in mitochondrial ultrastructure. These findings suggest that PRP can alleviate ferroptosis and promote cellular recovery.</div></div><div><h3>Conclusions</h3><div>The study demonstrates the potential of PRP as a therapeutic intervention in IVDD by mitigating ferroptosis in NP cells, offering a new theoretical basis for PRP treatment in degenerative disc diseases.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"41 ","pages":"Article 101900"},"PeriodicalIF":2.3,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heparin-binding of the human chitinase-like protein YKL-40 is allosterically modified by chitin oligosaccharides","authors":"Unnur Magnusdottir ,&nbsp;Finnbogi R. Thormodsson ,&nbsp;Lilja Kjalarsdottir ,&nbsp;Hordur Filippusson ,&nbsp;Johannes Gislason ,&nbsp;Kristinn Ragnar Oskarsson ,&nbsp;Jens G. Hjorleifsson ,&nbsp;Jon M. Einarsson","doi":"10.1016/j.bbrep.2024.101908","DOIUrl":"10.1016/j.bbrep.2024.101908","url":null,"abstract":"<div><div>The chitinase-like protein YKL-40 (CHI3L1) has been implicated in the pathophysiology of inflammation and cancer. Recent studies highlight the growing interest in targeting and blocking the activity of YKL-40 to treat cancer. Some of those targeting-strategies have been developed to directly block the heparin-affinity of YKL-40 with promising results. This study explores how short chain chitooligosaccharides (ChOS) affect the heparin-binding affinity of YKL-40. Our findings reveal that ChOS act as allosteric effectors, decreasing the heparin-binding affinity of YKL-40 in a size- and dose-dependent manner. Our results provide insights into the heparin affinity of YKL-40 and how ChOS can be used to target the heparin activity of YKL-40 in diseases. Since ChOS has many beneficial properties, such as being non-toxic and biodegradable, these results provide intriguing opportunities for applying them as allosteric effectors of the heparin-binding affinity of YKL-40.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"41 ","pages":"Article 101908"},"PeriodicalIF":2.3,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study on metabolic disorders in rat liver induced by different times after scalds","authors":"Zhian Chen ,&nbsp;Hui Lin ,&nbsp;Xixiong Su ,&nbsp;Wenmang Xu ,&nbsp;Wei Fang ,&nbsp;Guangping Ruan ,&nbsp;Zhen Wang ,&nbsp;Guangchao Xu ,&nbsp;Rongqing Pang","doi":"10.1016/j.bbrep.2024.101904","DOIUrl":"10.1016/j.bbrep.2024.101904","url":null,"abstract":"<div><div>Previous studies have confirmed that burns and scalds can lead to metabolic disorders in the liver. However, the effects of severe burns at various time points on liver lipid metabolism disorders, as well as the relationship between these disorders and liver function, metabolism, and infection, have not yet been investigated.This study established a SD rat scald model, macroscopic observation of weight changes, histological staining, Western blot detection of fat browning and metabolic indicators, reverse transcription quantitative polymerase chain reaction analysis of the expression of liver new fat generation genes, determination of liver function and inflammatory indicators.The results show that steam scalding of 30 % of the back skin surface area of rats for 30, 20, and 10 s can result in severe skin scalds. Liver Oil Red O staining revealed fat deposition in the scald group, which became more pronounced with longer scald durations. The fat deposition was most evident on the fifth day post-scald and gradually returned to normal over time. This phenomenon is primarily attributed to elevated liver function indicators, including TBIL, ALT, and AST, in the scald group compared to the control group. Additionally, there was activation of peripheral blood inflammatory cells (WBC, MON, NEU,TNF-α, IL-6, and IL-10) and infiltration of inflammatory cells in the liver, along with liver cell edema. The honeycomb-like appearance of peripheral epididymal fat and the significant increase in the expression of lipolytic proteins (UCP1, ATGL, HSL, and P-HSL) were also observed, alongside abnormal expression of key genes (CES and SCD1) associated with liver neovascularization. The changes are caused by the combined effects of these factors.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"41 ","pages":"Article 101904"},"PeriodicalIF":2.3,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating combined hypoxia and stemness indices for prognostic transcripts in gastric cancer: Machine learning and network analysis approaches","authors":"Sharareh Mahmoudian-Hamedani ,&nbsp;Maryam Lotfi-Shahreza ,&nbsp;Parvaneh Nikpour","doi":"10.1016/j.bbrep.2024.101897","DOIUrl":"10.1016/j.bbrep.2024.101897","url":null,"abstract":"<div><h3>Introduction</h3><div>Gastric cancer (GC) is among the deadliest malignancies globally, characterized by hypoxia-driven pathways that promote cancer progression, including stemness mechanisms facilitating invasion and metastasis. This study aimed to develop a prognostic decision tree using genes implicated in hypoxia and stemness pathways to predict outcomes in GC patients.</div></div><div><h3>Materials and methods</h3><div>GC RNA-seq data from The Cancer Genome Atlas (TCGA) were analyzed to compute hypoxia and stemness scores using Gene Set Variation Analysis (GSVA) and the mRNA expression-based stemness index (mRNAsi). Hierarchical clustering identified clusters with distinct survival outcomes, and differentially expressed genes (DEGs) between clusters were identified. Weighted Gene Co-expression Network Analysis (WGCNA) identified modules and hub genes associated with clinical traits. Overlapping DEGs and hub genes underwent functional enrichment, protein-protein interaction (PPI) network analysis, and survival analysis. A prognostic decision tree was constructed using survival-associated shared genes.</div></div><div><h3>Results</h3><div>Hierarchical clustering identified six clusters among 375 TCGA GC patients, with significant survival differences between cluster 1 (low hypoxia, high stemness) and cluster 4 (high hypoxia, high stemness). Validation in the GSE62254 dataset corroborated these findings. WGCNA revealed modules linked to clinical traits and survival, with functional enrichment highlighting pathways like cell adhesion and calcium signaling. The decision tree, based on genes such as <em>AKAP6</em>, <em>GLRB</em>, and <em>RUNX1T1</em>, achieved an AUC of 0.81 (training) and 0.67 (test), demonstrating the utility of combined scores in patient stratification.</div></div><div><h3>Conclusion</h3><div>This study introduces a novel hypoxia-stemness-based prognostic decision tree for GC. The identified genes show promise as prognostic biomarkers, warranting further clinical validation.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"41 ","pages":"Article 101897"},"PeriodicalIF":2.3,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11729012/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}