Frontiers in Molecular Biosciences最新文献

{"title":"CCDC138 overexpression predicts poor prognosis and highlights ciliopathy-linked mechanisms in uterine corpus endometrial carcinoma.","authors":"Aiping Wang, Fang Yang, Chunhua Zhang, Shi Li, Han Fu","doi":"10.3389/fmolb.2025.1622496","DOIUrl":"10.3389/fmolb.2025.1622496","url":null,"abstract":"<p><strong>Introduction: </strong>Uterine corpus endometrial carcinoma (UCEC) is a prevalent malignancy of the female reproductive system with increasing incidence, necessitating the identification of molecular mechanisms and biomarkers. While coiled-coil domain-containing protein 138 (CCDC138) is implicated in ciliopathies and cancer, its role in UCEC remains underexplored.</p><p><strong>Methods: </strong>We integrated transcriptomic and proteomic data from the Cancer Genome Atlas (TCGA), Clinical Proteomic Tumor Analysis Consortium (CPTAC), and Genotype-Tissue Expression (GTEx). Bioinformatics approaches, including weighted gene co-expression network analysis (WGCNA), singlesample gene set enrichment analysis (ssGSEA), machine learning, and survival analysis, were employed to assess CCDC138 expression and its functional relevance in UCEC. <i>In vitro</i> experiments involved CCDC138 knockdown, followed by CCK8 and EdU assays and qPCR for mTOR, S6K1, and p21 expression.</p><p><strong>Results: </strong>CCDC138 was significantly overexpressed at mRNA and protein levels in UCEC and correlated with poor overall survival. ssGSEA revealed associations with oncogenic pathways, including mTOR, p53/Rb, and MYC/MYCN. High CCDC138 expression was linked to reduced stromal and immune scores, indicating altered immune cell infiltration and tumor microenvironment. Drug sensitivity analysis showed increased responsiveness to chemotherapeutic agents like 5-fluorouracil and alpelisib in high-CCDC138 tumors. Protein-protein interaction analysis identified interactions with DCTN2 and CEP72. <i>In vitro</i>, CCDC138 knockdown reduced cell proliferation and downregulated mTOR, S6K1, and p21 mRNA expression.</p><p><strong>Discussion: </strong>These findings underscore CCDC138's role in UCEC progression, immune modulation, and therapeutic responsiveness, highlighting its potential as a prognostic biomarker and therapeutic target. Its shared relevance in UCEC and ciliopathies suggests broader implications for targeted therapies.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1622496"},"PeriodicalIF":3.9,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12370488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of swimming training on cecum microorganisms and metabolites in rats with high fat diet.","authors":"Chuan Dong, Ling Chen, Dengpan Li, Xuefeng Zhang, Yulong Chen","doi":"10.3389/fmolb.2025.1569239","DOIUrl":"10.3389/fmolb.2025.1569239","url":null,"abstract":"<p><p>Swimming is a whole-body aerobic exercise that has preventive and therapeutic effects on chronic metabolic diseases triggered by a high-fat diet. SPF grade rats (n = 48) were selected. They were divided into 4 groups (GB, GY, ZY and ZB) with 12 rats in each group. The GB and GY groups were fed high-fat chow during the pre-test period, and the ZY and ZB groups were fed normal chow. Swimming training was carried out in ZY and GY groups and no swimming exercise in GB and ZB groups in the later part of the trial. Histopathological staining was performed on the cecum and liver of 48 rats. Physiological and biochemical indices such as ACP, ALP and AST were measured in the blood of the rats in each group, and 6 samples of cecum contents were taken from each group for metagenomics and widely targeted metabolomics. The results showed that AST, ALP, ACP, LDL, IL-6, TNF-α, and IL-1β were significantly lower in the GY group than in the GB group; the structural liver lesions were severe in the GB and GY groups; and the ZY group had higher levels of <i>Prevotellaceae</i>, <i>Muribaculaceae</i>, and <i>Spirochaetes</i>. In comparison with the GB group, the GY group showed significant increases in metabolites associated with metabolic pathways such as ABC transporters and sulfur metabolism. The results show that feeding high-fat diet can cause tissue and organ lesions, cecal microbe and metabolite structure changes in rats. However, swimming training increased the content of beneficial microorganisms and metabolites in rats' cecum. This study provides a theoretical basis for swimming exercise to alleviate metabolic disorders caused by high fat diet.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1569239"},"PeriodicalIF":3.9,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12371242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144949000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The potential role of non-coding RNAs in acute kidney injury: a focus on natural medicine treatment.","authors":"Yuxin Guo, Yanru Zhao, Hanqing Zhang, Yunze Xing, Yaxuan Fang, Dingyuan Zheng, Hanqi Yang, Yanheng Qiao, Bo Yang","doi":"10.3389/fmolb.2025.1648526","DOIUrl":"10.3389/fmolb.2025.1648526","url":null,"abstract":"<p><p>Acute kidney injury (AKI) is a complex clinical disease characterized by sophisticated molecular pathways. Non-coding RNAs (ncRNAs), including lncRNAs, miRNAs, and circRNAs, play a pivotal role. This review focuses on the role of ncRNAs in AKI pathogenesis and their potential as biomarkers for early detection and therapeutic intervention. We carried out an extensive examination of the expression patterns, functional roles, and molecular mechanisms of lncRNAs, miRNAs, and circRNAs in AKI, as well as their relevance to treatments with natural medicines. Our findings underscore the dualistic nature of ncRNAs in AKI, acting as both protective and detrimental factors that influence key biological processes includes inflammation, oxidative stress, and apoptosis. We also point out the possible importance of other ncRNA types, such as snoRNAs and snRNAs, in AKI pathophysiology. This review provides a holistic perspective on the role of ncRNAs in AKI and lays the theoretical groundwork for the creation of innovative therapeutic strategies and biomarkers.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1648526"},"PeriodicalIF":3.9,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12367480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shared molecular profiles of post-laser vision correction ectasia and keratoconus with key differences in <i>CADPS</i>, <i>CPT1B</i>, <i>CIITA</i>, and <i>TBC1D4</i>.","authors":"Katarzyna Jaskiewicz-Rajewicz, Alicja Wysocka, Magdalena Maleszka-Kurpiel, Eliza Matuszewska-Mach, Jakub Wozniak, Rafal Ploski, Jan Matysiak, Malgorzata Rydzanicz, Marzena Gajecka","doi":"10.3389/fmolb.2025.1616675","DOIUrl":"10.3389/fmolb.2025.1616675","url":null,"abstract":"<p><strong>Introduction: </strong>Post-laser vision correction (post-LVC) ectasia is a serious complication that is observed in 0.033%-0.66% of corneal refractive surgeries. Similar to keratoconus (KTCN), post-LVC ectasia is classified under the category of \"ectatic diseases.\" We hypothesize that although the mechanistic aspects of post-LVC ectasia and KTCN are distinct, there are notable similarities in the epithelial responses, including shared molecular features.</p><p><strong>Methods: </strong>A total of 11 post-LVC ectasia, 8 mild myopia (controls), and 28 KTCN patients were included in a retrospective multiomics case-control study. The corneal epithelium (CE) samples obtained from the subjects were separated into different <i>topographic regions</i> (<i>TRs: central, middle,</i> and <i>peripheral</i>), and a total of 159 experimental samples were subjected to transcriptome (RNA-Seq) and proteome (MALDI-TOF/TOF MS/MS) profiling. The results were then verified/validated using reverse transcription quantitative polymerase chain reaction, immunofluorescence staining, and confocal microscopy in the extended sample set (n = 21).</p><p><strong>Results: </strong>The residual stromal bed, stromal ablation depth, and percent tissue altered indices were found to best predict the risk of post-LVC ectasia. From comparisons of post-LVC ectasia and KTCN, interferon-alpha and interferon-gamma hallmarks were found to be downregulated in the <i>central</i> and <i>middle TRs</i> of the CE of patients with post-LVC ectasia. Downregulation of <i>CADPS</i> gene expression was confirmed in all three <i>TRs</i> in the extended CE sample set. Cytoplasmic localizations of the CIITA and TBC1D4 proteins, which are the candidate post-LVC ectasia-specific biomarkers, were demonstrated in the CE samples.</p><p><strong>Discussion: </strong>The assessment of <i>CADPS, CPT1B, CIITA</i>, and <i>TBC1D4</i> gene expressions could enhance the risk estimation of ectasia in patients. Apart from differences in the transcription and inflammation processes, the CE of patients with post-LVC ectasia exhibits molecular features similar to KTCN.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1616675"},"PeriodicalIF":3.9,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12364684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using machine learning methods to investigate the role of volatile organic compounds in non-alcoholic fatty liver disease.","authors":"Chih-Hao Shen, Ruei-Hao Huang, Yaw-Kuen Li, Ta-Wei Chu, Dee Pei","doi":"10.3389/fmolb.2025.1631265","DOIUrl":"10.3389/fmolb.2025.1631265","url":null,"abstract":"<p><strong>Aims: </strong>Approximately 25%-30% of the global population is affected by non-alcoholic fatty liver disease (NAFLD). This study aimed to explore whether NAFLD could be effectively detected using 341 volatile organic compounds (VOCs) via 10 machine learning (Mach-L) algorithms in a cohort of 1,501 individuals.</p><p><strong>Methods: </strong>Participants were selected from the Taiwan MJ cohort, which includes comprehensive demographic, biochemical, lifestyle, and VOCs data. NAFLD was diagnosed by experienced gastroenterologists. Exhaled breath samples were collected using a 1.0-L aluminum bag (late expiratory fraction) and analyzed with selected-ion flow-tube mass spectrometry. Ten Mach-L techniques were employed to evaluate two predictive models: Model 1 (demographic, lifestyle, and biochemical data), and Model 2 (Model 1 + VOCs), assessed using area under the receiver operating characteristic curve (AUC).</p><p><strong>Results: </strong>Subjects with NAFLD had significantly higher values for age, BMI, blood pressure, and other biomedical markers, except for eGFR and HDL-C. Key predictors of NAFLD included BMI, triglycerides (TG), uric acid (UA), fasting plasma glucose (FPG), γ-GT, gender, LDL-C, and sleep duration. The addition of VOCs to Model 1 improved the AUC from 0.722 ± 0.149 to 0.770 ± 0.264 (p < 0.001). Ten VOCs were identified as the most influential, in order of importance: 2-propanol, acetone, butyl 2-methylbutanoate, diethylethanolamine, urethane, β-caryophyllene, furfural, tridecane, 4-methyloctanoic acid, and (S)-2-methyl-1-butanol.</p><p><strong>Conclusion: </strong>Incorporating VOCs into traditional demographic, biochemical, and lifestyle data significantly enhanced the model's predictive performance. This suggests that VOCs may be associated with the underlying pathophysiology of NAFLD.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1631265"},"PeriodicalIF":3.9,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12365380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ALKBH5 in development: decoding the multifaceted roles of m⁶A demethylation in biological processes.","authors":"Xinye Zhang, Linfang Zhou, Cheng Tian, Huangheng Tao","doi":"10.3389/fmolb.2025.1599487","DOIUrl":"10.3389/fmolb.2025.1599487","url":null,"abstract":"<p><p>N⁶-methyladenosine (m⁶A), an abundant internal RNA modification in eukaryotes, serves as a dynamic post-transcriptional regulator of gene expression by influencing RNA splicing, stability, translation, and decay. This reversible epitranscriptomic mechanism, which is mediated by methyltransferase (writers), demethylase (erasers), and m⁶A-binding proteins (readers), is pivotal in diverse biological contexts. Among m⁶A erasers, alkylation repair homolog protein 5 (ALKBH5), an Fe(II)/α-ketoglutarate-dependent dioxygenase, is the second to be discovered and one of the most significant demethylases. Mounting evidence underscores ALKBH5's role in modulating developmental programming, where it coordinates processes such as lineage specification, organogenesis, and tissue homeostasis. This review systematically deciphers the multifaceted contributions of ALKBH5-mediated m⁶A demethylation to developmental biology. We synthesize recent advances elucidating how ALKBH5-driven m⁶A erasure dynamically regulates transcriptomic rewiring during embryogenesis, reproductive development, cardiac development, central nervous system development, immune system development, pancreatic organogenesis, osteogenic/odontogenic differentiation, adipogenesis, and angiogenesis. These revelations not only deepen our understanding of epitranscriptomic regulation in ontogeny but also illuminate therapeutic avenues for developmental anomalies and regenerative medicine.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1599487"},"PeriodicalIF":3.9,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12358293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144882578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammation-nutrition biomarker model for survival prediction in lung cancer patients with concurrent tuberculosis.","authors":"Hongqi Zhou, Zihao Zhao, Jinhai Wang, Weiyun Jin, Bensong Xian, Lindi Li, XiangWen Nie, WeiWei Wu, Ran Chen, QiZhen Xie, HaiXia Wu, WeiWei Jiang, Min Tang, YuXin Li","doi":"10.3389/fmolb.2025.1624131","DOIUrl":"10.3389/fmolb.2025.1624131","url":null,"abstract":"<p><strong>Objectives: </strong>To explore the prognostic value of eight inflammation-nutrition biomarkers in patients with lung cancer and tuberculosis as no multidimensional prognostic models for this comorbid population are available currently.</p><p><strong>Methodology: </strong>A retrospective study included 100 patients with lung cancer and tuberculosis admitted to a tertiary hospital from October 2019 to October 2024. Eight inflammation-nutrition markers (NLR, PLR, SII, LMR, PNI, HALP, HRR, ALB/GLB) were chosen as predictors while overall survival (OS) was the major event. Feature selection was implemented by LASSO regression; a Cox proportional hazards model was established afterwards. The nomogram's performance was assessed by ROC curve and C-index as well as the calibration using bootstrap resampling. The statistical power was calculated by PowerSurvEpi and sensitivity analyses were implemented to test the robustness of the model.</p><p><strong>Results: </strong>There were six predictors remaining in the final model including diabetes, ECOG PS, NLR, PNI, HRR and RDW. Among them, ECOG PS was an independent prognostic factor (HR = 1.76, p = 0.04). The nomogram achieved a good performance (C-index = 0.71), an AUC of 0.693 for 3-year OS as well as an excellent calibration (Bootstrap P > 0.05). In the high-risk subgroup with ECOG PS ≥ 2 and NLR>8, the 5-year survival rate was close to zero. The model achieved an adequate statistical power (83%, α = 0.05). Sensitivity analysis revealed an significant interaction between ECOG PS and NLR (p = 0.032) and NLR>8 was the most robust threshold for this interaction.</p><p><strong>Conclusion: </strong>This is the first study to establish and validate a combined inflammation-nutrition prognostic model for patients with lung cancer and tuberculosis. Our model provides a quantitative tool to stratify individual risk and offers evidence for the usage of nutritional interventions in high-risk patients.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1624131"},"PeriodicalIF":3.9,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12358283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144882579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunoglobulin A carries sulfated and <i>O</i>-acetylated <i>N</i>-glycans primarily at the tailpiece site - strategies for site-specific <i>N</i>-glycan identification.","authors":"Frania J Zuniga-Banuelos, Greta Lemke, Marcus Hoffmann, Udo Reichl, Erdmann Rapp","doi":"10.3389/fmolb.2025.1595173","DOIUrl":"10.3389/fmolb.2025.1595173","url":null,"abstract":"<p><p>Sulfated <i>N-</i>glycans from human immunoglobulin A (IgA) were recently discovered via glycomic approaches. However, their site-specific description is still pending. Certain <i>N-</i>glycan structures at specific <i>N-</i>glycosylation sites in IgA are crucial for microbial neutralization and effector functions. For instance, sialylated <i>N-</i>glycans on the C-terminal tailpiece mediate anti-viral activity by interfering with sialic-acid-binding viruses. Sulfated <i>N-</i>glycan epitopes can be ligands for viral proteins and thus play a role in the immune response. In this study, we performed a site-specific screening for sulfated and other rare <i>N-</i>glycans in two commercially available human serum IgA samples employing an in-depth <i>N-</i>glycoproteomic approach, previously developed by us. We found evidence of complex-type and hybrid-type <i>N-</i>glycans containing sulfated <i>N-</i>acetylhexosamine (sulfated HexNAc) attached to the <i>N-</i>glycosylation sites in the tailpiece and the C_H2 domain of both IgA subclasses. Also, complex-type <i>N-</i>glycan compositions bearing <i>O-</i>acetylated sialic acid were identified primarily at the tailpiece site. Surprisingly, <i>N-</i>glycans bearing glucuronic acid were identified in the commercial IgA samples, but from peptides of \"contaminant\" glycoproteins. A detailed comparison of the <i>N-</i>glycosylation profiles of human serum IgA samples from two suppliers showed such <i>N-</i>glycans with sulfated HexNAc consistently in higher abundance in the tailpiece region. These findings have not been described before for a site-specific glycopeptide analysis. Overall, our work provides strategies for performing a dedicated site-specific search for sulfated and <i>O-</i>acetylated <i>N-</i>glycans that can be easily transferred, e.g., to human IgA derived from mucosal tissues, milk, or saliva. We expect that a wider and deeper micro-heterogeneity description of clinically relevant glycoproteins, such as immunoglobulins, can expand the screening for biomarkers or treatment options.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1595173"},"PeriodicalIF":3.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12353717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144872321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comprehensive analysis of the tryptophan metabolism-related gene signature to predict the prognosis of esophageal squamous cell carcinoma based on multi-omics.","authors":"Zhengjie Wu, Zhiping Liu, Yukun Wang, Geling Teng, Xiaodong Li, Tong Lu, Fangning Hu, Shuo Wu, Guanqiang Ma, Hua Zhang","doi":"10.3389/fmolb.2025.1613539","DOIUrl":"10.3389/fmolb.2025.1613539","url":null,"abstract":"<p><strong>Background: </strong>Tryptophan (Trp) metabolism plays a vital role in tumor development and outcomes. However, Trp in esophageal squamous cell carcinoma (ESCC) remains poorly understood. We aimed to explore the role and mechanism of Trp metabolism in ESCC.</p><p><strong>Methods: </strong>We integrated single-cell RNA (scRNA) sequencing, bulk transcriptome, proteomics, and microbiome data from public databases. Tryptophan-related cell populations and their interactions were explored using the \"seurat\" R package at the single-cell level. Least absolute shrinkage and selection operator (LASSO) and univariate Cox regression were used to select prognostic TrpGs and construct a risk model. The overall survival, immune infiltration, checkpoint expression, drug sensitivity, and microbiota composition between high- and low-risk groups were evaluated. Independent prognostic factors were identified via multivariate Cox analysis and validated by qPCR analysis, and a nomogram was constructed for survival prediction.</p><p><strong>Results: </strong>We identified 28 differentially expressed tryptophan-related genes (DE-TrpGs), and fibroblasts emerged as the cell type with the highest TrpG score, although reduced in ESCC. Eighteen DE-TrpGs showed downregulation in tumor fibroblasts at the single-cell level. Fibroblast-epithelial communication involved the LAMININ, HSPG, and AGRN pathways. Five prognostic TrpGs (MAOA, AKR1A1, ALDH9A1, HAAO, and ALDH2) were selected to construct the risk model. The expression of MAOA, AKR1A1, ALDH9A1, HAAO, and ALDH2 was significantly downregulated in ESCC tumor tissues compared to non-tumor tissues. High-risk patients showed poorer overall survival (OS), distinct immune cell infiltration, elevated expression of KIR2DL1, LGALS9, TNFRSF18, and TNFRSF4, increased sensitivity to imatinib and axitinib, resistance to multiple chemotherapeutics, and reduced <i>Fusobacteria</i> and <i>Tenericutes</i> abundance. HAAO, ALDH2, and lymph node stage were identified as independent prognostic factors and were used to develop a predictive nomogram.</p><p><strong>Conclusion: </strong>We identified a Trp metabolism-associated fibroblast population in the ESCC tumor microenvironment (TME) and developed a five-gene TrpG signature for prognostic prediction in ESCC patients.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1613539"},"PeriodicalIF":3.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12353700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144872318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing head and neck cancer detection accuracy in digitized whole-slide histology with the HNSC-classifier: a deep learning approach.","authors":"Haiyang Yu, Wang Yu, Yuan Enwu, Jun Ma, Xin Zhao, Linlin Zhang, Fang Yang","doi":"10.3389/fmolb.2025.1652144","DOIUrl":"10.3389/fmolb.2025.1652144","url":null,"abstract":"<p><p>Head and neck squamous cell carcinoma (HNSCC) represents the sixth most common cancer worldwide, with pathologists routinely analyzing histological slides to diagnose cancer by evaluating cellular heterogeneity, a process that remains time-consuming and labor-intensive. Although no previous studies have systematically applied deep learning techniques to automate HNSCC TNM staging and overall stage prediction from digital histopathology slides, we developed an inception-ResNet34 convolutional neural network model (HNSC-Classifier) trained on 791 whole slide images (WSIs) from 500 HNSCC patients sourced from The Cancer Genome Atlas (TCGA) Head and Neck Squamous Cell dataset. Our pipeline was designed to distinguish cancerous from normal tissue and to predict both tumor stage and TNM classification from histological images, with the dataset split at the patient level to ensure independence between training and testing sets and performance evaluated using comprehensive metrics including receiver operating characteristic (ROC) analysis, precision, recall, F1-score, and confusion matrices. The HNSC-Classifier demonstrated exceptional performance with areas under the ROC curves (AUCs) of 0.998 for both cancer/normal classification and TNM system stage prediction at the tile level, while cross-validation showed high precision, recall, and F1 scores (>0.99) across all classification tasks. Patient-level classification achieved AUCs of 0.998 for tumor/normal discrimination and 0.992 for stage prediction, significantly outperforming existing approaches for cancer stage detection. Our deep learning approach provides pathologists with a powerful computational tool that can enhance diagnostic efficiency and accuracy in HNSCC detection and staging, with the HNSC-Classifier having potential to improve clinical workflow and patient outcomes through more timely and precise diagnoses, serving as an automated decision support system for histopathological analysis of HNSCC.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1652144"},"PeriodicalIF":3.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12353728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144872320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}