Biology Direct最新文献

{"title":"High oxidative phosphorylation represented by UQCRFS1 marks CD8 + tumor-infiltrating lymphocytes exhaustion in diffuse large B-cell lymphoma.","authors":"Yiming Yang, Yaqi Shu, Zujun Qin, Yi Zeng, Kexin Chen, Xin Liu, Shunhai Jian, Qiqi Zhu","doi":"10.1186/s13062-025-00684-1","DOIUrl":"10.1186/s13062-025-00684-1","url":null,"abstract":"<p><strong>Background: </strong>Metabolic alterations are closely associated with the exhaustion and immune deficiency of CD8⁺ tumor-infiltrating lymphocytes (TILs), while little is known about diffuse large B-cell lymphoma (DLBCL). This study aimed to elucidate the significance of the metabolic alterations in exhausted CD8⁺TILs and its underlying regulatory mechanism in DLBCL.</p><p><strong>Methods: </strong>The metabolic alterations in exhausted CD8⁺TILs in DLBCL were evaluated through single-cell RNA sequencing (scRNA-seq). The crucial metabolic pathway and its significance in the biological function of exhausted CD8⁺TILs were investigated by scRNA-seq and RNA sequencing. The marker gene in crucial metabolic pathway, and its correlations between exhaustion status, the tumor microenvironment (TME) composition, clinicopathological characteristics, prognosis, and immune checkpoint blockade (ICB) therapy efficacy were evaluated by scRNA-seq, RNA sequencing, immunohistochemistry, and RT-qPCR. Furthermore, the underlying regulatory mechanism involved in the metabolic alteration related to CD8⁺TILs exhaustion was explored through scRNA-seq, RNA sequencing, and somatic mutation analysis.</p><p><strong>Results: </strong>Our study illustrated the metabolic heterogeneity in CD8⁺TILs, and demonstrated that oxidative phosphorylation (OXPHOS) was the crucial pathway in CD8⁺TILs exhaustion. The high OXPHOS activity indicated the immune deficiency in exhausted CD8⁺TILs, and UQCRFS1 was identified as a marker gene. High UQCRFS1 indicated the immunosuppressive TME, severe clinicopathological characteristics, including activated B-cell-like subtype, high IPI and PS score, advanced stage, dismal prognosis, and resistance to ICB therapy. Furthermore, MYC-related signaling and P2RY8 mutation in DLBCL may regulate the UQCRFS1 expression in exhausted CD8⁺TILs.</p><p><strong>Conclusions: </strong>Our study highlights the importance of OXPHOS activity in CD8⁺TILs exhaustion and suggests its possible regulatory mechanism, which is feasible in clinical evaluation and beneficial for novel immunotherapeutic approaches in DLBCL.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"92"},"PeriodicalIF":4.9,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12345122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144844452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"m⁶A methylation-mediated lncRNA RNF144A-AS1 promotes hepatocellular carcinoma progression through the miR-1301-3p/RNF38 pathway.","authors":"Minyu Kong, Wendong Li, Hao Li, Yifan Jing, Min Xu, Yuting He, Wenzhi Guo","doi":"10.1186/s13062-025-00681-4","DOIUrl":"10.1186/s13062-025-00681-4","url":null,"abstract":"<p><strong>Background: </strong>Globally, HCC is still one of the most common cancers. N6-methyladenosine (m⁶A) modifications and long-stranded noncoding RNAs (lncRNAs) play key roles in regulating HCC progression. The role of the lncRNA RNF144A-AS1, a newly identified lncRNA, in HCC is unclear.</p><p><strong>Methods: </strong>In HCC, RNF144A-AS1 expression level and its effect on prognosis were investigated by bioinformatics. CCK-8, EdU, scratch assay, and Transwell assays were used to detect the impact of RNF144A-AS1 on hepatocellular carcinoma malignancy. Assays using MeRIP-qPCR, RIP, and Actinomycin D were used to study the effects of m⁶A methylation on hepatocellular carcinoma malignant phenotypes. Revealing the potential mechanism of action of RNF144A-AS1 by luciferase reporter gene assay, PCR, and Western blot assays, and Nude mice subcutaneous load cell and lung metastasis models were used to verify the effect of RNF144A-AS1 on the malignant phenotype of tumors in vivo.</p><p><strong>Results: </strong>The lncRNA RNF144A-AS1 was significantly upregulated in HCC, and it was significantly associated with poor prognosis. Functionally, HCC cells with RNF144A-AS1 knockdown were inhibited in terms of proliferation, migration, and invasion. Further studies in vivo confirmed that RNF144A-AS1 knockdown inhibited tumor cell growth and metastasis. Mechanistically, METTL3 increased the m⁶A modification and stability of RNF144A-AS1 in an IGF2BP1-associated manner. In addition, RNF144A-AS1 was inhibited by sponge-like miR-1301-3p to inhibit RNF38 degradation, thereby promoting the HCC malignant phenotype.</p><p><strong>Conclusion: </strong>The RNF144A-AS1 gene is affected by METTL3/IGF2BP1 methylation and encourages liver cancer proliferation and metastasis by increasing expression of RNF38 through sponge-like miR-1301-3p. RNF144-AS1 promises to be a therapeutic target for HCC.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"91"},"PeriodicalIF":4.9,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12306006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 genus Akkermansia is populated by a multitude of biological species with a wide distribution in the animal kingdom.","authors":"Cristian Molteni, Diego Forni, Rachele Cagliani, Manuela Sironi","doi":"10.1186/s13062-025-00680-5","DOIUrl":"10.1186/s13062-025-00680-5","url":null,"abstract":"<p><strong>Background: </strong>The mucin-degrading bacterium Akkermansia muciniphila has attracted enormous interest for its beneficial effects on human health. However, growing evidence suggests that the Akkermansia genus is populated by several species that differ in phenotypic characteristics and association with human traits.</p><p><strong>Results: </strong>We present the most comprehensive phylotaxonomic analysis of Akkermansia genomes in terms of sample size and host representation. By applying approaches based on average nucleotide identities and on the biological species concept, we show that the Akkermansia genus comprises at least 31 species, 13 of which can be detected in humans. The largest species diversity is contributed by non-human and non-mouse animals, and limited evidence of species-specificity is evident, with several Akkermansia species detected in phylogenetically distant animals. Analysis of accessory gene content among species also failed to reveal species-specific or diet-specific associations, but rather reflected genome size. Thus, A. muciniphila and A. ignis have, on average, small genomes and retain a part of genes that characterize either A. massiliensis or A. sp004167605/A. biwaensis. Finally, investigation of the population structure of A. muciniphila, the species that has been more intensely investigated due to its effects on human health, clearly distinguished two phylogroups corresponding to AmIa and AmIb. However, analysis of laboratory mouse-derived genomes revealed that additional populations, specific to these animals, exist. Such populations show limited evidence of admixture, suggesting bottleneck or competition effects.</p><p><strong>Conclusions: </strong>Our data support the concept that the genetic diversity of Akkermansia should be taken into account in experimental settings. They also call for sequencing efforts to characterize the wider genetic diversity of Akkermansia bacteria.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"90"},"PeriodicalIF":4.9,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12288247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CLIC2 regulates immunosuppression and macrophage differentiation in genomically stable gastric cancer.","authors":"Viviana Longo, Pellegrino Mazzone, Giovanni Calice, Pietro Zoppoli, Giuseppina Di Paola, Giuseppe Cesta, Margherita Luongo, Claudia Sabato, Sabino Russi, Simona Laurino, Tiziana Notarangelo, Giuseppe Patitucci, Chiara Balzamo, Valeria Lucci, Elena Amendola, Giuseppina Amodio, Paolo Remondelli, Valentina Pagliara, Maria Rita Milone, Roberta Guadagno, Cristofaro De Stefano, Ferdinando De Vita, Geppino Falco, Francesco Albano","doi":"10.1186/s13062-025-00666-3","DOIUrl":"10.1186/s13062-025-00666-3","url":null,"abstract":"<p><p>Chloride intracellular channels (CLICs) are a family of six evolutionarily conserved proteins with diverse functions. Previously, we identified CLIC2, as the fifth-ranked master regulator associated with diffuse-type gastric cancer (dGC) showing increased expression in tumors. Here we used bulk, as well as single cell sequencing datasets of dGC, to demonstrate for the first time a direct association of CLIC2 with the microsatellite stable GC and, furthermore, the expression of CLIC2 in macrophages (MCs), and endothelial cells (ECs) populating gastric tissue. We generated CLIC2 knock-out THP-1 monocytic cells (THP-1CLIC2_KO) determining that while CLIC2 deletion had no observable effect on monocytes, THP-1CLIC2_KO macrophages exhibited significant morphological changes, including increased membrane protrusions, and upregulated expression of CD11b, CD11c, CD80, and CD86 markers. Furthermore, cytokine secretion profiling of THP-1CLIC2_KO differentiated cells revealed elevated secretion of CCL8, alongside reduced secretion of IL-1β, IL-6, and osteoprotegerin (OPG). Additionally, we observed increased phosphorylation of Shp1 phosphatase with the concomitant absence of Stat3 phosphorylation, which impaired downstream signaling, in line with the evidence that Clic2 interacts with both Shp1 and Stat3. Based on these findings, we suggest that CLIC2 plays a pivotal role in regulating monocyte-to-macrophage differentiation by modulating the Stat3 signaling pathway, thus enhancing gastric cancer progression by establishing a tumor-permissive microenvironment.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"89"},"PeriodicalIF":4.9,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12282021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ferroptosis-disulfidptosis-related CHMP6 is a clinico-immune target in colorectal cancer.","authors":"Yifei Zhu, Huixia Huang, Jiayu Chen, Keji Chen, Yanxi Yao, Yaxian Wang, Yuxue Li, Zhibing Qiu, Dawei Li, Ping Wei","doi":"10.1186/s13062-025-00676-1","DOIUrl":"10.1186/s13062-025-00676-1","url":null,"abstract":"<p><strong>Background: </strong>Ferroptosis and disulfidptosis are newly discovered forms of regulated cell death that play critical roles in cancer progression, metabolism, and immune evasion. However, their interplay and combined influence on colorectal cancer (CRC) progression remain insufficiently understood.</p><p><strong>Methods: </strong>We developed a ferroptosis-disulfidptosis-related gene (FDRG) score using machine-learning algorithms to analyze gene modifications associated with these pathways in CRC, utilizing data from the TCGA and GEO databases. The model was externally validated, and associations with clinical outcomes, immune infiltration, mutational landscapes, immunotherapy responses, and drug sensitivity were explored. Key genes were further investigated through bioinformatics and in vitro experiments.</p><p><strong>Results: </strong>We constructed an 8-gene risk model with strong prognostic value, stratifying CRC patients into high- and low-risk groups with significant differences in clinical characteristics, immune cell infiltration, and therapeutic responses. Among these genes, CHMP6 was identified as a previously uncharacterized tumor suppressor in CRC. Beyond its inhibitory effect on tumor cell proliferation, migration, and invasion, CHMP6 was found to play a critical role in modulating anti-tumor immunity. Our findings established CHMP6 as a dual-function tumor suppressor that not only restrains tumor progression but also enhances immune-mediated tumor control.</p><p><strong>Conclusions: </strong>The FDRG score is a robust tool for predicting CRC prognosis, tumor microenvironment dynamics, and response to immunotherapy. CHMP6 emerged as a promising tumor suppressor and potential therapeutic target, offering new insights into CRC treatment strategies.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"88"},"PeriodicalIF":5.7,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12278666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 role of SH3RF2 in lung squamous cell carcinoma and M2 polarization: insights into LZTS2 ubiquitination.","authors":"Jie Yang, Zhongfei Jia, Juan Li, Chao Jiang, Xin Zhao, Yuxiang Wang, Xiaoguo Ma, Xinjian Xu","doi":"10.1186/s13062-025-00677-0","DOIUrl":"10.1186/s13062-025-00677-0","url":null,"abstract":"<p><strong>Background: </strong>Despite significant advancements in therapeutic approaches for lung cancer, the prognosis of lung squamous cell carcinoma (LUSC) remains suboptimal, underscoring the critical need to identify novel molecular targets and develop targeted therapeutic strategies. Through bioinformatic analysis, SH3RF2 was identified as a gene significantly upregulated in LUSC patients, and its high expression was strongly associated with lower survival rates. However, no significant differences in expression or survival correlation were observed in lung adenocarcinoma. Notably, SH3RF2, an E3 ubiquitin ligase characterized by three SH3 domains, has not been systematically investigated in LUSC pathogenesis.</p><p><strong>Results: </strong>Mechanistic investigations found that SH3RF2 promoted tumor cell proliferation, upregulated M2 markers (Arg-1, CD163, IL-10), increased CD206 + subpopulation of M0 THP-1 cells and enhanced migration and invasion of M0 THP-1 cells. SH3RF2 promoted the nuclear translocation of β-catenin. Furthermore, ICG-001, the inhibitors of β-catenin pathway, alleviated the above effects of SH3RF2. In vivo tumorigenesis experiments found that SH3RF2 promoted tumor growth and increased the proportion of M2 cells. Proteomic analysis revealed that SH3RF2 interacted with LZTS2 and regulated the ubiquitination of LZTS2 with RING domain. Overexpression of LZTS2 attenuated SH3RF2-induced nuclear translocation of β-catenin, suppressed cellular migration and invasion, and inhibited M2 polarization promoted by SH3RF2 overexpression. The combination of SH3RF2 knockdown and radiotherapy inhibited the growth of tumor compared with SH3RF2 knockdown or radiotherapy alone.</p><p><strong>Conclusions: </strong>This study demonstrates the functionality of SH3RF2 in both potentiating tumor progression and inducing M2 macrophage polarization through coordinated regulation of LZTS2 degradation and β-catenin nuclear translocation. These findings establish a novel mechanistic framework and propose SH3RF2-associated signaling axes as promising therapeutic targets for LUSC.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"87"},"PeriodicalIF":5.7,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12269186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Affibodies as valuable tool to prevent β2m aggregation under lysosomal-like conditions.","authors":"Cristina Visentin, Giulia Rizzi, Wen Yin, Mathilde Hotot, Dipambita Roy, Torbjörn Gräslund, Riccardo Capelli, Stefano Ricagno","doi":"10.1186/s13062-025-00679-y","DOIUrl":"10.1186/s13062-025-00679-y","url":null,"abstract":"","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"86"},"PeriodicalIF":5.7,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12265214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicle-enriched secretome of adipose-derived stem cells upregulates clusterin to alleviate doxorubicin-induced apoptosis in cardiomyocytes.","authors":"Wan-Tseng Hsu, Shinji Kobuchi, Tung-Chun Russell Chien, I-Chun Chen, Shohei Hamada, Masayuki Tsujimoto, I-Lin Tsai, Yun-Sheng Wong, Kuan-Hsuan Tung, Ying-Zhen He","doi":"10.1186/s13062-025-00664-5","DOIUrl":"10.1186/s13062-025-00664-5","url":null,"abstract":"<p><p>Doxorubicin (DOX) is a potent chemotherapeutic widely used against various cancers, but its clinical application is limited by DOX-induced cardiotoxicity (DIC). This study explored the cardioprotective potential of extracellular vesicle-enriched secretome derived from adipose stem cells (EVS_ASC) in mitigating DOX-induced apoptosis in cardiomyocytes. Adipose-derived stem cells were cultured, and their conditioned medium and extraceullular vesicles were isolated and characterized according to the Minimal Information for Studies of Extracellular Vesicles 2023 guidelines. HL-1 cardiomyocytes were pretreated with EVS_ASC before exposure to 1 µM DOX. Cell viability was assessed via the cell counting kit-8 assay, while apoptosis markers and survival mediators were evaluated through Western blotting. RNA sequencing identified differentially expressed genes, including clusterin (Clu), which was further quantified using an enzyme-linked immunosorbent assay. The functional role of clusterin was validated through siRNA-mediated knockdown. EVS_ASC significantly improved cell viability in DOX-exposed cardiomyocytes and reduced the cleaved caspase-3 to procaspase-3 ratio. Clusterin expression was highest in EVS_ASC-treated cells, and its knockdown markedly increased caspase-3 cleavage, confirming its pivotal role in cardioprotection. Moreover, EVS_ASC enhanced the phosphorylation of AKT, Bcl2-associated agonist of cell death, and glycogen synthase kinase-3β, implicating PI3K/AKT pathway activation in clusterin upregulation and anti-apoptotic effects. These findings demonstrate that EVS_ASC mitigates DOX-induced apoptosis in cardiomyocytes through clusterin upregulation and PI3K/AKT pathway activation. Clusterin is identified as a potential biomarker for evaluating EVS_ASC efficacy. While EVS_ASC shows promise as a cardioprotective strategy against DIC, further studies are needed to optimize its therapeutic safety by addressing potential oncogenic risks.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"84"},"PeriodicalIF":5.7,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12265340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autophagy inhibition potentiates anti-cancer activity of Sunitinib in kidney cancer cells.","authors":"Simone Patergnani, Pietro Zampieri, Nicoletta Bianchi, Carmelo Ippolito, Roberta Gafà, Giovanni Lanza, Mariusz R Wieckowski, Paolo Pinton, Gianluca Aguiari","doi":"10.1186/s13062-025-00671-6","DOIUrl":"10.1186/s13062-025-00671-6","url":null,"abstract":"","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"82"},"PeriodicalIF":5.7,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular mechanisms of efferocytosis imbalance in the idiopathic pulmonary fibrosis microenvironment: from gene screening to dynamic regulation analysis.","authors":"Qian Jin, Yi Kang, Wenwen Jin, Ying Liu, Qian Chen, Jian Liu, Yali Guo, Yuguang Wang","doi":"10.1186/s13062-025-00658-3","DOIUrl":"10.1186/s13062-025-00658-3","url":null,"abstract":"<p><strong>Background: </strong>Idiopathic pulmonary fibrosis (IPF) is a chronic progressive pulmonary disease characterized by alveolar structural destruction and fibrosis. In recent years, efferocytosis has been recognized as playing a crucial role in the occurrence and progression of IPF. This study aimed to identify and regulate key efferocytosis-related genes to elucidate their potential roles and clinical significance in IPF.</p><p><strong>Methods: </strong>IPF-related datasets (GSE32537) were obtained from the Gene Expression Omnibus (GEO) database. Differential gene expression analysis and weighted gene coexpression network analysis (WGCNA) were applied to identify key genes associated with IPF, intersecting them with efferocytosis-related genes (ERGs) to obtain IPF-ERGs. Protein‒protein interaction (PPI) network construction and enrichment analysis were performed to elucidate the potential functions of these genes in IPF. Seven machine learning algorithms were employed to screen for hub genes with high diagnostic value. The GSE70866 dataset was used for validation, and a nomogram was constructed. Additionally, the CIBERSORT algorithm was used to analyze immune infiltration levels, and transcriptomic validation of the hub genes was conducted in animal experiments.</p><p><strong>Results: </strong>A total of 21 IPF-ERGs were identified, and machine learning further identified TLR2, ATG7, SPHK1, and ICAM1 as hub genes, which were significantly upregulated in the IPF group. Immune infiltration analysis revealed a significant increase in the infiltration levels of immune cell subsets, including memory B cells, CD8 + T cells, and resting dendritic cells, in the IPF group. Further clinical correlation analysis revealed a strong association between the expression levels of the hub genes and pulmonary function. A nomogram was constructed on the basis of the hub genes and validated for its potential clinical application. Consensus clustering classified IPF patients into two subtypes: C1, which was primarily by metabolic pathway activation, and C2, which was enriched in inflammatory and immune pathways. Transcriptomic analysis of animal experiments also confirmed the upregulation of hub gene expression in IPF.</p><p><strong>Conclusion: </strong>This study identified TLR2, ATG7, SPHK1, and ICAM1 as four key hub genes, revealing their potential diagnostic value and biological functions in IPF. These genes may serve as potential diagnostic biomarkers and therapeutic targets, providing new insights for precision treatment.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"83"},"PeriodicalIF":5.7,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}