Biochemistry and Biophysics Reports最新文献

{"title":"Prognostic value and immune infiltration analysis of a novel lactylation-related gene signature in endometrial cancer","authors":"Liqin Gu ,&nbsp;Chunnian Zhang ,&nbsp;Minjuan Xu ,&nbsp;Fang Peng ,&nbsp;Ruo-Hui Huang ,&nbsp;Deping Luo","doi":"10.1016/j.bbrep.2025.102056","DOIUrl":"10.1016/j.bbrep.2025.102056","url":null,"abstract":"<div><h3>Background</h3><div>Lactylation has been implicated in tumor growth, proliferation, and metastasis; however, its precise relationship with cancer remains poorly understood. This study aims to elucidate the role of lactylation-related genes (LRGs) in the development of endometrial cancer (EC).</div></div><div><h3>Methods</h3><div>We utilized data from The Cancer Genome Atlas (TCGA) database to analyze the expression and mutation patterns of LRGs in EC. Univariate Cox regression analysis and Lasso-Cox regression analysis were employed to identify prognosis-related genes and construct a risk model. EC samples were stratified into high-risk and low-risk groups based on the risk values derived from the model. These groups were validated using both training and validation cohorts. Additionally, we assessed differences in the immune microenvironment, tumor mutation burden (TMB), and drug response between the high-risk and low-risk groups.</div></div><div><h3>Results</h3><div>Differentially expressed genes (DEGs) between EC and control samples were identified, and their intersection with LRGs yielded differentially expressed lactylation-related genes (DLRGs). A total of six prognostic DLRGs (PFKM, H3C1, SIRT3, VIM, WAS, and LSP1) were selected and used to construct an EC risk model. Significant differences in prognosis, immune microenvironment, TMB, and drug sensitivity were observed between the high-expression and low-expression groups.</div></div><div><h3>Conclusion</h3><div>LRGs play a significant role in endometrial cancer by influencing cell growth, the immune microenvironment, and drug response. The six DLRGs included in the risk model may serve as potential prognostic markers and therapeutic targets for EC.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102056"},"PeriodicalIF":2.3,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multidirectional therapeutic effects of synthesized HMGB1 peptide on liver cirrhosis in mice","authors":"Masaki Mito ,&nbsp;Atsunori Tsuchiya ,&nbsp;Soichi Ishii ,&nbsp;Takafumi Tonouchi ,&nbsp;Kaito Furuyama ,&nbsp;Ryo Jinbo ,&nbsp;Nobutaka Takeda ,&nbsp;Hiroyuki Abe ,&nbsp;Katsuto Tamai ,&nbsp;Shuji Terai","doi":"10.1016/j.bbrep.2025.102061","DOIUrl":"10.1016/j.bbrep.2025.102061","url":null,"abstract":"<div><h3>Aim</h3><div>Liver cirrhosis is a serious disease characterized by liver dysfunction and severe fibrosis; however, no breakthrough drugs have effectively improved fibrosis, making it an unmet medical need. We have previously reported that the HMGB1 peptide, synthesized from box A of the HMGB1 protein, ameliorates liver fibrosis and is a promising candidate for fibrosis-improving drugs against liver cirrhosis. In this study, we used spatial analysis to observe treatment-induced changes over time.</div></div><div><h3>Methods</h3><div>Liver cirrhosis was induced in C57BL/6J mice using carbon tetrachloride (CCl4) injections, followed by HMGB1 peptide treatment. To assess the temporal effects of HMGB1 on the liver in a CCl4-induced cirrhosis mouse model, we used GeoMx spatial analysis. We focused on αSMA-positive active hepatic stellate cells (HSCs), F4/80-positive macrophages, and CK8/18-positive hepatocytes to determine how each cell type was affected over time. Statistical analyses were conducted using GraphPad Prism9, with significance set at p &lt; 0.05.</div></div><div><h3>Results</h3><div>In cirrhotic mice, we first observed a decrease in the number of activated HSCs over time, two weeks after treatment initiation. Macrophage-associated genes ceased to induce fibrosis-related pathways early in the treatment. This suggests that the effect of macrophages on fibrosis was weakened by the treatment. We also confirmed that lipid metabolism of hepatocytes may be improved during treatment. Furthermore, <em>Cxcl12</em> and <em>Ccl25</em> expression were induced in the peptide-treated group, indicating possible cell migration to the liver.</div></div><div><h3>Conclusion</h3><div>Over time, macrophages followed by HSCs, showed the most notable changes with treatment, resulting in improved fibrosis. The HMGB1 peptide drug also affected lipid metabolism in hepatocytes, suggesting a positive therapeutic effect on steatohepatitis. Elevated factors that promote cell migration may have also enhanced the healing effect.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102061"},"PeriodicalIF":2.3,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144131336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The miR-146a-associated HDAC2 regulation of PI3K is involved in pancreatitis in vitro","authors":"Ding-wen Zhong ,&nbsp;Xiang-tian Zeng ,&nbsp;Wen-hui Chen ,&nbsp;Xian-yu Huang ,&nbsp;Jia-xin Liu ,&nbsp;Yong-hui Liao","doi":"10.1016/j.bbrep.2025.102057","DOIUrl":"10.1016/j.bbrep.2025.102057","url":null,"abstract":"<div><h3>Purpose</h3><div>To investigate the association between miR-146a/HDAC2 and their regulatory roles on the PI3K expression during pancreatitis.</div></div><div><h3>Methods</h3><div>Rat pancreatic AR42J cells were treated with LPS for simulating pancreatitis. Expression levels of inflammatory factors (IL-6, TNF-α) and miR-146a were d<strong>etected to</strong> determine the optimal LPS concentration for establishing an in vitro pancreatitis model<strong>.</strong> Cell proliferation and apoptosis were analyzed using CCK-8 and flow cytometry<strong>.</strong> Immunofluorescence was performed to assess co-localization of HDAC2 and PI3K. ELISA quantified TNF-α and IL-6 levels in cell supernatants. A dual-luciferase assay verified the targeting relationship between miR-146a and HDAC2.</div></div><div><h3>Results</h3><div>Compared to controls, the cell proliferation ability of the pancreatitis model group was decreased, whereas TSA and miR-146a mimic interventions restored proliferation. The expression of IL-6 and TNF-αin the LPS group was higher than that in the control group, and their expression decreases in the TSA and miR-146a mimic intervention group. Besides the dual luciferase detected the targeting relationship between miR-146a and HDAC2, the immunofluorescence showed co-localization of HDAC2 and PI3K.</div></div><div><h3>Conclusions</h3><div>TSA and miR-146a mimic enhance proliferation and reduce inflammation in pancreatitis cells. The miR-146a/HDAC2 axis may mediate therapeutic effects in pancreatitis by modulating the PI3K expression.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102057"},"PeriodicalIF":2.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144089154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibrinogen based resuscitation mitigates lung injury in mice with bacterial pneumonia after hemorrhagic shock","authors":"Feng Wu,&nbsp;Jody Cantu,&nbsp;Rosemary A. Kozar","doi":"10.1016/j.bbrep.2025.102054","DOIUrl":"10.1016/j.bbrep.2025.102054","url":null,"abstract":"<div><div>While pneumonia is a common complication following severe trauma, the optimal treatment for this complication remains unclear. Our previous studies have shown that fibrinogen and fresh frozen plasma (FFP) administration have beneficial effects in mitigating lung dysfunction in mice after trauma and hemorrhagic shock (HS), due to the restoration of endothelial syndecan-1. The objective of the current study was to test these two therapeutics in a combined model of HS and pneumonia. We hypothesized they would be equally protective. C57BL/6 mice underwent HS [mean arterial pressure (MAP) of 40–45 mmHg for 1 h] and fluid resuscitation with lactated Ringer's (LR), fibrinogen concentrate (FIB, 5 mg/mouse in LR), and FFP all at 1x bled volume. Mice were then infected by P. aeruginosa [strain PA103, 3 × 10⁴ colony-forming units (CFUs)] via intratracheal instillation. After 24 h, mice were euthanized, and lung tissue, bronchoalveolar lavage (BAL) fluid, and plasma were harvested for assays. HS + P. aeruginosa infection induced increases in permeability, syndecan-1 cleavage, and MMP9 activation in the lungs, and an increase in plasma shed syndecan-1. These alterations were significantly attenuated by fibrinogen but not by FFP, implying that fibrinogen prevented the endothelial injury. Additionally, lung tissue MPO and neutrophil infiltration were significantly decreased after HS + P. aeruginosa. These alterations were reversed by fibrinogen but not by FFP, indicating fibrinogen is able to correct the neutrophil deficiency state caused by HS + P. aeruginosa infection. Taken together, these results suggest that fibrinogen has therapeutic benefit in a model of HS and pneumonia.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102054"},"PeriodicalIF":2.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144089155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SSR-based molecular characterization of Verticillium wilt resistance in Iranian cotton cultivars","authors":"Sanaz Shahbazi ,&nbsp;Sara Ghaffarian ,&nbsp;Mohammad Razinataj ,&nbsp;Mohammad Reza Zangi ,&nbsp;Rasmieh Hamid ,&nbsp;Bahman Panahi","doi":"10.1016/j.bbrep.2025.102059","DOIUrl":"10.1016/j.bbrep.2025.102059","url":null,"abstract":"<div><div>Verticillium wilt (VW) is one of the most devastating diseases affecting cotton (<em>Gossypium</em> spp.), causing significant yield losses worldwide. The development of resistant cultivars is a primary strategy for managing this disease; however, conventional breeding approaches often encounter challenges in balancing resistance with high yield potential. This study aimed to assess the genetic diversity of 25 cotton cultivars using simple sequence repeat (SSR) markers and to identify key polymorphic markers associated with VW resistance. A total of 16 SSR markers were utilized, of which five (DPL405, DPL752, DPL866, DPL890, and DPL0022) were polymorphic. The polymorphism information content (PIC) values ranged from 0 to 0.49, with DPL405, DPL866, and DPL890 being the most informative. Principal coordinates analysis (PCoA) demonstrated genetic differentiation between resistant and sensitive cultivars, with the first axis explaining 41.19 % of the total variation. Resistant cultivars such as Leader, Golestan, and Arya clustered distinctly from sensitive varieties, confirming the effectiveness of the selected markers in genetic differentiation. Despite the promising results, key limitations include the relatively low overall marker polymorphism and the limited number of SSRs used, which may constrain broader genomic coverage and resolution. Nonetheless, the findings provide valuable insights for cotton breeding programs and highlight the potential of SSR markers in supporting marker-assisted selection (MAS) for Verticillium wilt resistance.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102059"},"PeriodicalIF":2.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144089153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Benchmarking AlphaMissense pathogenicity predictions against APP, PSEN1, and PSEN2 variants of unknown significance","authors":"Joshua Pillai ,&nbsp;Sophia Liu ,&nbsp;Kijung Sung ,&nbsp;Linda Shi ,&nbsp;Chengbiao Wu","doi":"10.1016/j.bbrep.2025.102049","DOIUrl":"10.1016/j.bbrep.2025.102049","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by progressive cognitive decline. Over 200 pathogenic mutations in <em>amyloid-β precursor protein (APP)</em>, <em>presenilin-1</em> (<em>PSEN1</em>), and <em>presenilin-2</em> (<em>PSEN2</em>), have been implicated in AD. Yet, many rare and common variants have not been completely classified as protective or benign, risk-modifiers, or pathogenic, which is important for research on the disease mechanisms and discovery of treatment methods. The majority of these variants are missense mutations, and there is an active need for computational approaches to accurately predict their molecular consequences. AlphaMissense (AM) is a novel technology that uses population frequency data along with structural and sequential contexts from AlphaFold to predict the pathogenicity of missense mutations. Herein, we sought to evaluate the capabilities of AM on 114 variants of unknown significance (VUS), including 56 missense variants of <em>PSEN1</em>, 25 of <em>APP</em>, and 33 of <em>PSEN2</em> by benchmarking its prediction against their respective Aβ isoform levels <em>in vitro</em>, respectively. We found that the AM scores correlated moderately well with the critical Aβ42/Aβ40 biomarker and Aβ40 levels in the transmembrane proteins compared to weaker correlations in traditional approaches, including Combined Annotation Dependent Depletion (CADD) v1.7, evolutionary model of variant effect (EVE), and Evolutionary Scale Modeling-1b (ESM-1B). Yet, there were non-significant correlations identified with Aβ42 levels in all models. Furthermore, we found that AM does not rely completely on structural contexts from AlphaFold2, as it accurately predicted the effects of known variants on residues with a low predicted local distance difference test (pLDDT) score. Additionally, based on the receiver operating characteristic-area under the curve analysis (ROC-AUC), we found that AM retained a high performance on 263 validated variants of these amyloidogenic genes, and performed the greatest compared to other models for the 114 VUS. We believe this is the first study to provide comprehensive characterization and validation of AM in comparison to the widely utilized pathogenicity scoring models for VUS involved in proteins implicated in AD.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102049"},"PeriodicalIF":2.3,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144069322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel small molecule that enhances lysyl hydroxylase 2 activity and matrix mineralization","authors":"Saori Tomiku ,&nbsp;Atsushi Kasamatsu ,&nbsp;Reo Fukushima ,&nbsp;Tomoaki Saito ,&nbsp;Ryunosuke Nozaki ,&nbsp;Akiko Suganami ,&nbsp;Yutaka Tamura ,&nbsp;Mitsuo Yamauchi ,&nbsp;Katsuhiro Uzawa","doi":"10.1016/j.bbrep.2025.102053","DOIUrl":"10.1016/j.bbrep.2025.102053","url":null,"abstract":"<div><div>Lysyl hydroxylase 2 (LH2), encoded by the <em>procollagen lysine 2-oxoglutarate 5-dioxygenase 2</em> (<em>Plod2</em>) gene, catalyzes the hydroxylation of lysine residues in the fibrillar collagen telopeptides. This post-translational modification is essential for forming the stable hydroxylysine-aldehyde derived collagen cross-links that play a critical role in collagen stability, mechanical strength, and bone formation. Defective LH2 activities have been implicated in bone disorders including Bruck syndrome, however, effective agents that control LH2 activity have not been developed until now. In this study, using <em>in silico</em> docking simulations, we identified a small molecule (KS122-0485428) that specifically binds LH2, and assessed the effects of this compound on collagen cross-linking, cell proliferation, and mineralization using the murine osteoblastic cell line MC3T3-E1. While KS122-0485428 did not affect cell proliferation and LH2 expression, it significantly accelerated mineralization. The hydroxylysine-aldehyde derived collagen cross-links were also significantly increased at the expense of the lysine-aldehyde derived cross-link. These results demonstrate that KS122-0485428 enhances LH2 activity leading to accelerated mineralization. Thus, this novel LH2 activator has the potential as a therapeutic agent for bone repair and regeneration.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102053"},"PeriodicalIF":2.3,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144069255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing PCR amplification of GC-rich nicotinic acetylcholine receptor subunits from invertebrates","authors":"Muhammad Tanveer Khan ,&nbsp;Coralie Belgrano ,&nbsp;Lucien Rufener ,&nbsp;Tor Einar Horsberg ,&nbsp;Marit Jorgensen Bakke","doi":"10.1016/j.bbrep.2025.102052","DOIUrl":"10.1016/j.bbrep.2025.102052","url":null,"abstract":"<div><div>Polymerase chain reaction (PCR) is a widely used molecular biology technique for amplifying specific DNA sequences. However, amplifying templates with a high GC content (&gt;60 %) poses challenges owing to strong hydrogen bonds and secondary structure formation, hindering DNA polymerase activity and primer annealing. Given these challenges, our study focuses on refining PCR protocols for the nicotinic acetylcholine receptor subunits, pivotal for understanding signal transduction in various organisms and potential important drug targets. We optimized the PCR protocol to efficiently amplify the beta1 and alpha1 subunits of the nicotinic acetylcholine receptor from <em>Ixodes ricinus</em> (<em>Ir-nAChRb1</em>) and <em>Apis mellifera</em> (<em>Ame-nAChRa1</em>). <em>Ir-nAChRb1</em> and <em>Ame-nAChRa1</em> have open reading frames of 1743 and 1884 bp, respectively, with overall GC contents of 65 % and 58 %. Various DNA polymerases and organic additives have been evaluated at different annealing temperatures. The tailored protocol incorporated organic additives, such as DMSO and betaine, increased enzyme concentration, and adjusted annealing temperatures. This study demonstrates the importance of a multipronged approach involving various organic molecules, DNA polymerases, PCR conditions, and primer adjustments to overcome the challenges of amplifying GC-rich sequences.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102052"},"PeriodicalIF":2.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144069253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic mechanisms of icariin in intervertebral disc degeneration: A critical narrative review","authors":"LiLun Zhong ,&nbsp;ZhenWen Xu ,&nbsp;YingJun Peng ,&nbsp;SongPeng Li ,&nbsp;An Liu ,&nbsp;ZhiDong Lin","doi":"10.1016/j.bbrep.2025.102047","DOIUrl":"10.1016/j.bbrep.2025.102047","url":null,"abstract":"<div><div>Intervertebral disc degeneration (IDD), a primary cause of low back pain, involves complex pathological mechanisms. Current research emphasizes identifying strategies to mitigate degenerative processes and enhance intrinsic disc repair. Emerging evidence highlights the therapeutic potential of icariin (ICA) in promoting disc repair and delaying IDD progression. ICA exerts its effects through multiple mechanisms, including anti-inflammatory actions, oxidative stress mitigation, modulation of bone and collagen metabolism, and inhibition of ferroptosis and pyroptosis. This review synthesizes current research on ICA's therapeutic applications in IDD management.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102047"},"PeriodicalIF":2.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143947208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibroblast activation protein-α is a potential prognostic biomarker related to ferroptosis in head and neck squamous cell carcinoma","authors":"Kun Cui ,&nbsp;Shifu Tang ,&nbsp;Jing Wei ,&nbsp;Wanping Wang ,&nbsp;Yaoming Deng","doi":"10.1016/j.bbrep.2025.102046","DOIUrl":"10.1016/j.bbrep.2025.102046","url":null,"abstract":"<div><div>Head and neck squamous cell carcinoma (HNSC) is the sixth most prevalent cancer worldwide, with approximately 700,000 new cases each year. Due to its heterogeneity, reliable biomarkers are crucial for guiding treatment. Fibroblast activation protein (FAP) has been implicated in HNSC progression, but its specific involvement in ferroptosis and the ceRNA network is still not well understood.</div><div>In this study, data from The Cancer Genome Atlas (TCGA) HNSC dataset were analyzed to examine the relationship between FAP expression and drug sensitivity, clinical features, methylation status, ferroptosis, immune infiltration, prognosis, and ceRNA networks. The results showed that FAP expression was significantly higher in HNSC tissues compared to normal tissues and was linked to increased sensitivity to 25 antitumor drugs, as well as poorer prognosis and unfavorable clinicopathological features. Lower methylation levels of FAP were also associated with higher mRNA expression and worse outcomes.</div><div>Thirteen ferroptosis-related genes (FRGs) were identified, and four distinct ferroptosis clusters were characterized, with one cluster (C3) showing better survival rates. FAP was further linked to multiple immune cell types, immune markers, and key pathways such as PI3K-Akt and TGF-β. Additionally, a ceRNA network (NOP14-AS1/hsa-miRNA-30e-5p/FAP) was established, which correlated with overall survival in HNSC patients. These findings suggest that FAP may serve as a promising prognostic biomarker in HNSC, influencing both ferroptosis and the tumor microenvironment, providing potential targets for future therapies.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102046"},"PeriodicalIF":2.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144069254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}