Molecular immunology最新文献

{"title":"Caveolin-1 protects against liver injury and lipid accumulation in alcoholic fatty liver via ferroptosis resistance","authors":"Weiju Xue ,&nbsp;Ning Guo ,&nbsp;Liang Shan ,&nbsp;Zhengsheng Zhang ,&nbsp;Yuquan Sun ,&nbsp;Yong Wang ,&nbsp;Xing Fang ,&nbsp;Xiuzhen Liu ,&nbsp;Jianjun Liu ,&nbsp;Chengmu Hu","doi":"10.1016/j.molimm.2025.02.012","DOIUrl":"10.1016/j.molimm.2025.02.012","url":null,"abstract":"<div><div>Alcoholic fatty liver (AFL) is one of the most common chronic liver diseases globally with complex and controversial pathogenesis. Recent evidence suggests that iron overload and lipid peroxidation are risk factors for AFL. Caveolin-1 (CAV1) is an important signal platform that can maintain lipid homeostasis during the development of non-alcoholic fatty liver. Here, we studied the effect of CAV1 on ferroptosis in AFL. The AFL mouse model was established by chronic-plus-binge alcohol feeding. In vitro, AML-12 cells were incubated with ethanol and oleic acid for 48 h. We found alcohol-induced AFL triggered ferroptosis and decreased CAV1 expression. Overexpression of CAV1 by CAV1 scaffolding domain peptides (CSD) attenuated liver injury and hepatic steatosis, as well as inhibited ferroptosis in AFL mice. Additionally, the effects of CAV1 on ferroptosis-related protein levels (such as SLC7A11, GPX4, and ACSL4) and lipid accumulation were reversed by its small interfering RNA administration. Ferroptosis agonist (Erastin) treatment abrogated CAV1 plasmid-mediated ferroptosis resistance and steatosis alleviation. Collectively, the results revealed a crucial role of CAV1 in preventing hepatic steatosis and ferroptosis in alcohol-induced liver injury, which may identify potential targets for the treatment of AFL.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"181 ","pages":"Pages 53-65"},"PeriodicalIF":3.2,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143592460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BATF participates in airway inflammation of neutrophilic asthma via regulating Th17 cells activation","authors":"Chunming Liu ,&nbsp;Xue Yang ,&nbsp;Yiling Tan ,&nbsp;Yuxin Wang ,&nbsp;Jian Lan ,&nbsp;Pu Yang ,&nbsp;Dongchi Zhao","doi":"10.1016/j.molimm.2025.03.001","DOIUrl":"10.1016/j.molimm.2025.03.001","url":null,"abstract":"<div><div>Neutrophilic asthma (NA) is a common subtype of non-eosinophilic asthma, characterized by the infiltration of neutrophils. Basic leucine zipper transcription factor ATF-like (BATF) is the nuclear transcription factor that initiates lymphocyte differentiation. The mechanism by which BATF affects T cell differentiation leading to neutrophil accumulation in NA lung tissue remains unclear. In this study, we established murine models of NA through sensitization with ovalbumin (OVA) /complete Freund's adjuvant and subsequent challenge with OVA/lipopolysaccharide. Using these models, we systematically investigated pathological alterations, inflammatory cell infiltration patterns, and cytokine expression profiles in murine lung tissues. The impact of glucocorticoid intervention on the pathology of airway inflammation in NA mice was assessed, and the markers associated with lymphocyte differentiation RORγt and FoxP3 were detected. Furthermore, on the basis of BATF knockdown, the distribution of lymphocyte subtypes and the effect on neutrophil activity in the lung tissues of NA mice were observed. Our results revealed that both BATF and IL-17A showed high expression in NA lung tissue, and neutrophils were predominant in bronchoalveolar lavage fluid (BALF). Glucocorticoid treatment failed to alleviate lung histopathological lesion and exacerbated neutrophil accumulation in NA. Inhibiting BATF could significantly reduce neutrophil accumulation, as well as downregulate IL-17A expression, thus alleviating lung histopathological injury in NA. BATF was involved in mainly regulating naïve lymphocyte differentiation to T helper cell 17 (Th17) rather than regulatory T cells (Tregs). Our results demonstrate that BATF plays an important proinflammatory role in neutrophil asthma, and the inhibition of BATF could reduce lung inflammation by reducing IL-17A, acting as a potential therapeutic target.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"181 ","pages":"Pages 40-52"},"PeriodicalIF":3.2,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143592461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutrophil-derived exosomal S100A8 aggravates lung injury in sepsis by inducing pyroptosis","authors":"Xinxin Li ,&nbsp;Wei Zhou ,&nbsp;Liangliang Zhou,&nbsp;Yingbin Li,&nbsp;Xufeng Wu,&nbsp;Jianjun Chen","doi":"10.1016/j.molimm.2025.03.003","DOIUrl":"10.1016/j.molimm.2025.03.003","url":null,"abstract":"<div><div>Acute lung injury (ALI) is a common and life-threatening complication in patients with sepsis, with pro-inflammatory cell pyroptosis playing a crucial role in the associated organ damage. In this study, we aimed to identify potential therapeutic targets. Utilizing the GEO database (GSE232753), we analyzed the differentially expressed genes in the peripheral blood of healthy individuals and sepsis patients, identifying the significantly upregulated gene S100A8. Subsequently, we constructed a septic ALI model using lipopolysaccharide (LPS). Notably, S100A8 was highly expressed not only in serum and bronchoalveolar lavage fluid (BALF) but also in neutrophil exosomes. We then co-incubated BEAS-2B cells with neutrophil exosomes that were either treated or untreated with LPS. Cell proliferation activity was assessed using the CCK-8 assay, cell death was evaluated through propidium iodide (PI) staining, and the changes in pyroptosis indicators were detected via Western blot and ELISA. To further validate that LPS-induced neutrophil exosomes promote BEAS-2B cell pyroptosis through the delivery of S100A8, we conducted additional experiments involving the addition of S100A8 protein alone or S100A8 antibody in conjunction with neutrophil exosome treatment, followed by relevant assessments. Moreover, <em>in vivo</em> validation was also performed. Mechanistically, we revealed that S100A8 induces pyroptosis in BEAS-2B cells through the TLR4 signaling pathway. In conclusion, our findings provide new promising targets for the treatment of septic ALI.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"181 ","pages":"Pages 29-39"},"PeriodicalIF":3.2,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143577194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fructus arctii mitigates diabetic nephropathy via the Apoh/PPAR-γ pathway","authors":"Na Zhang ,&nbsp;Anhui Chen ,&nbsp;Yuwei Dong ,&nbsp;Deqiang Dou","doi":"10.1016/j.molimm.2025.02.017","DOIUrl":"10.1016/j.molimm.2025.02.017","url":null,"abstract":"<div><h3>Background</h3><div>Diabetic nephropathy (DN) is characterized by renal fibrosis and functional decline. Apolipoprotein H (Apoh) and Fructus arctii, a traditional medicinal plant, have demonstrated potential in treating metabolic and fibrotic disorders. This study Focused on revealing the roles of Apoh and Fructus arctii in mitigating DN.</div></div><div><h3>Methods</h3><div>Db/db mice served as an <em>in vivo</em> DN model, and mouse glomerular mesangial cells (mMCs) and renal tubular epithelial cells (mTECs) were treated with high glucose (HG) to simulate DN in vitro. Apoh silencing and overexpression were performed using shRNA and pcDNA3.1 vectors. Fructus arctii was administered to both cellular and animal models to assess its therapeutic potential. Cellular proliferation was measured using CCK-8 and EdU assays, while fibrosis markers were analyzed by Western blot, IHC and RT-qPCR. PPAR-γ pathway involvement was confirmed through treatment with the antagonist GW9662. Renal structural changes were evaluated with histological staining including H&amp;E, PAS, Masson’s trichrome, and picrosirius red staining.</div></div><div><h3>Results</h3><div>Apoh expression was markedly reduced in HG-treated cells and the kidneys of db/db mice. Overexpression of Apoh suppressed HG-induced proliferation in mMCs and mTECs by downregulating cyclin D1 and PCNA. Additionally, Apoh overexpression alleviated fibrosis by reducing Fibronectin, Collagen I, and α-SMA levels, effects mediated through the PPAR-γ pathway. Treatment with the PPAR-γ antagonist GW9662 reversed these protective effects. In db/db mice, Fructus arctii administration improved renal function by reducing blood glucose, proteinuria, and renal collagen deposition. It also alleviated fibrosis and enhanced Apoh and PPAR-γ expression. Silencing Apoh nullified the protective effects of Fructus arctii on cell proliferation and fibrosis, confirming its reliance on the Apoh/PPAR-γ pathway.</div></div><div><h3>Conclusion</h3><div>Fructus arctii alleviated DN progression by modulating cell proliferation and renal fibrosis via the Apoh/PPAR-γ pathway.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"181 ","pages":"Pages 18-28"},"PeriodicalIF":3.2,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143563443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cigarette smoke-exposed microparticles released from T lymphocytes contribute to autophagy and apoptosis dysfunction in pulmonary microvascular endothelial cells","authors":"Gang Chen ,&nbsp;Zhaoji Meng ,&nbsp;Pei Wang","doi":"10.1016/j.molimm.2025.02.020","DOIUrl":"10.1016/j.molimm.2025.02.020","url":null,"abstract":"<div><div>Cigarette smoke can cause dysfunction of the vascular endothelium; however, the underlying mechanisms have not been fully elucidated. We hypothesized that T lymphocyte-derived microparticles (TLMPs) are involved in cigarette-related diseases, especially those involving the vascular endothelium. The effect of cigarette smoke on the release of microparticles from human lymphocytes was investigated. The contributions of TLMPs induced by cigarette smoke to endothelial proliferation/apoptosis, autophagy and cytokine levels were also measured. Notably, the potential mechanism of autophagy and apoptosis dysfunction in endothelial cells was further examined. Cigarette smoke promoted the release of microparticles from T lymphocytes. TLMPs attenuated endothelial proliferation but promoted endothelial apoptosis/autophagy and the expression of proinflammatory cytokines, especially when T lymphocytes were preexposed to cigarette smoke. The potential mechanism may involve disorders of oxidative stress and STAT3 phosphorylation. In conclusion, cigarette smoke-exposed microparticles released from T lymphocytes contribute to autophagy and apoptosis dysfunction in pulmonary microvascular endothelial cells.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"181 ","pages":"Pages 9-17"},"PeriodicalIF":3.2,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143549964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The superantigen SEA binds to human γδ T cell receptor and activates γδ T cells with moderate MHC class II dependence","authors":"Sibel Uzunçayır ,&nbsp;Ganna Petruk ,&nbsp;Manuel Mata Forsberg ,&nbsp;Claudia Arasa ,&nbsp;Eva Sverremark-Ekström ,&nbsp;Karin Lindkvist-Petersson","doi":"10.1016/j.molimm.2025.02.019","DOIUrl":"10.1016/j.molimm.2025.02.019","url":null,"abstract":"<div><div>Bacterial toxins, called superantigens, are produced by <em>Staphylococcus aureus</em> and are known to activate γδ T cells. γδ T cells contribute to long-lasting immunity against bacterial skin infections caused by <em>S. aureus</em>. γδ T cells are a distinct subgroup of T cells containing the T cell receptor (TCR) γ and δ chains. The γδ TCR harbouring the variable chains TRGV9/TRDV2 is the most common TCR in human peripheral blood and is known to be activated by superantigens and are also promising candidates for tumor immunotherapy. However, detailed analyses of antigen binding to γδ TCR have been severely hampered by difficulties in producing large amounts of γδ TCR. In this study, we report a protocol to produce recombinant γδ TCR (TRGV9/TRDV2) by fusing the variable domains γδ TCR with the constant domains of αβ TCR. Subsequently, binding analyses were executed applying microscale thermophoresis showing a clear binding between superantigen and the γδ TCR in the micro molar range. In addition, the superantigen SEA was shown to induce cytokine expression in γδ T cells with moderate MHC dependence, suggesting that other receptors can act as antigen presenting molecules upon γδ T cell activation. These results pave the way towards a better understanding of superantigen recognition by the γδ T cells and facilitates the future use of γδ TCR in cellular tumor immunotherapy.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"181 ","pages":"Pages 1-8"},"PeriodicalIF":3.2,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143549963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"circSTIL mediates pirarubicin inhibiting the malignant phenotype of triple-negative breast cancer and acts as a biomarker in plasma exosomes","authors":"Jiahua Ji ,&nbsp;Min Li ,&nbsp;Kaixu Yan ,&nbsp;Jiulong Ma ,&nbsp;Dexian Wei ,&nbsp;Fan Zhang ,&nbsp;Sennan Qiao ,&nbsp;Peng Huang ,&nbsp;Wenqing Zhang ,&nbsp;Lu Li ,&nbsp;Wentao Zheng ,&nbsp;Liqun Ren","doi":"10.1016/j.molimm.2025.02.014","DOIUrl":"10.1016/j.molimm.2025.02.014","url":null,"abstract":"<div><div>In clinical practice, pirarubicin (THP) is a widely used triple-negative breast cancer (TNBC) agent. It has been found that circular RNAs (circRNAs) are involved in cancer treatment and progression. However, the biological function of circRNAs in TNBC and the relationship between THP and circRNAs remain poorly studied. circSTIL (hsa_circ_0000069) was screened and validated by bioinformatics analysis, demonstrating that it was highly expressed in TNBC cell lines and plasma exosomes, and correlated with a poor prognosis of patients. The expression level of circSTIL in patients’ plasma exosomes has potential diagnostic value in distinguishing TNBC from non-TNBC. In vitro studies confirmed that overexpression of circSTIL promotes the proliferation, migration, and invasion of MDA-MB-231 cells whereas silicification of circSTIL shows the reverse effect. Also, circSTIL mediates THP inhibiting the malignant phenotype of MDA-MB-231 cells. The above results suggested that circSTIL is a possible biomarker for the diagnosis, treatment, and prognosis of TNBC.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"180 ","pages":"Pages 86-95"},"PeriodicalIF":3.2,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel mechanistic insights into the comorbidity of anemia and rheumatoid arthritis: Identification of therapeutic targets","authors":"Cun Li ,&nbsp;Xiongzhi Shi,&nbsp;Shou Chen ,&nbsp;Xiaoming Peng ,&nbsp;Shaohui Zong","doi":"10.1016/j.molimm.2025.02.011","DOIUrl":"10.1016/j.molimm.2025.02.011","url":null,"abstract":"<div><h3>Objectives</h3><div>To investigate the mechanisms underlying the comorbidity of anemia and rheumatoid arthritis (RA) and identify promising therapeutic targets.</div></div><div><h3>Methods</h3><div>We assessed the phenotypic linkage between anemia and RA. Using the largest genome-wide association studies (GWAS) summary statistics of European populations, we scrutinized the causal association and shared genetic architecture between the two conditions using multiple complementary approaches.</div></div><div><h3>Results</h3><div>Logistic regression analysis confirmed a strong clinical association between anemia and RA. Using GWAS data, we identified a significant causal effect of RA on anemia and positive global genetic correlations between the two conditions (r_g (genotype) = 0.28, P = 9.6 × 10⁻⁷; r_g (gene expression) = 0.45, P = 2 × 10⁻³). After dividing the genome into 2495 independent regions, we identified 15 significant regions associated with both conditions, with 14 showing concordant effects. Fine-mapping at the SNP level revealed 72 % of RA-associated SNPs overlapped with anemia, most with concordant effects. Stratified Q-Q plots visualized the shared genetic enrichment, showing a 12-fold enrichment for RA conditional on anemia and 100-fold enrichment for anemia conditional on RA. Further analysis using conjFDR method pinpointed 14 pleiotropic loci, including several novel loci. Gene mapping identified 33 shared genes, with BLK and FAM167A further prioritized as the top two genes by SMR analysis. Enrichment analysis highlighted pathways related to inflammation, immune response, and iron metabolism. Blood and T cells showed significant tissue- and cell-type-specific enrichment.</div></div><div><h3>Conclusions</h3><div>This study provides novel insights into anemia-RA comorbidity mechanisms and identifies new drug targets for RA.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"180 ","pages":"Pages 74-85"},"PeriodicalIF":3.2,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143508221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"C-reactive protein attenuates CCl4-induced acute liver injury by regulating complement system activation","authors":"Zhao-Ming Tang ,&nbsp;Ping Yuan ,&nbsp;Ning Gao ,&nbsp;Jia-Geng Lei ,&nbsp;Mustafa Ahmed ,&nbsp;Yu-Xin Hua ,&nbsp;Ze-Rui Yang ,&nbsp;Qiu-Yu Li ,&nbsp;Hai-Yun Li","doi":"10.1016/j.molimm.2025.02.008","DOIUrl":"10.1016/j.molimm.2025.02.008","url":null,"abstract":"<div><div>Acute liver injury is liver dysfunction caused by multiple factors without any pre-existing liver disease. C-reactive protein (CRP) is an acute-phase protein produced by hepatocytes, serving as a marker of inflammation and tissue damage. However, its role in CCl₄-induced acute liver injury has not been elucidated. Here, we report that CRP protects against CCl₄-induced acute liver injury by regulating complement activation. CRP knockout exacerbates CCl₄-induced acute liver injury in mice and rats, markedly enhances tissue damage, and reduces survival. Administration of exogenous CRP to CRP-knockout mice rescues the CCl₄-induced liver injury phenotype. The protective effect of CRP is independent of its cellular receptor <em>FcγR2b</em> and early metabolic pathways. Instead, CRP suppresses the late-phase amplification of inflammation by inhibiting terminal complement pathway overactivation in injured hepatocytes via factor H recruitment. In complement C3 knockout (C3^-/-) mice, the protective effect of CRP against CCl₄-induced acute liver injury is lost. These results suggest that CRP can alleviate CCl₄-induced acute liver injury by regulating the complement pathway, providing a theoretical basis for CRP's potential involvement and regulation of disease severity.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"180 ","pages":"Pages 44-54"},"PeriodicalIF":3.2,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143488623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KRT14 is a promising prognostic biomarker of breast cancer related to immune infiltration","authors":"Siqi Liao ,&nbsp;Xin Zhang ,&nbsp;Lanhui Chen ,&nbsp;Jianning Zhang ,&nbsp;Weiyu Lu ,&nbsp;Mengou Rao ,&nbsp;Yifan Zhang ,&nbsp;Zijian Ye ,&nbsp;Deyana Ivanova ,&nbsp;Fangfang Li ,&nbsp;Xuemei Chen ,&nbsp;Yingxiong Wang ,&nbsp;Anchao Song ,&nbsp;Biao Xie ,&nbsp;Meijiao Wang","doi":"10.1016/j.molimm.2025.02.016","DOIUrl":"10.1016/j.molimm.2025.02.016","url":null,"abstract":"<div><h3>Background</h3><div>Breast cancer (BC) is the leading cancer among women globally, which has the highest incidence and mortality rate in over a hundred countries. This study was intended to discover a new prognostic biomarker, facilitating personalized treatment approaches.</div></div><div><h3>Methods</h3><div>RNA sequencing data from The Cancer Genome Atlas database and Gene Expression Omnibus database were utilized to download to evaluate expression levels and prognostic significance of Keratin 14 (KRT14). Methylation of KRT14 was also assessed. The CIBERSORT and single-sample gene set enrichment analysis algorithms were applied to explore the connection between KRT14 and the tumor microenvironment. Primary drugs' sensitivity and potential small molecule therapeutic compounds were analyzed through the \"pRRophetic\" R package and the Connectivity Map. The prognostic value of KRT14 was additionally corroborated through a comparison of protein levels in peritumoral and cancerous tissues via immunohistochemistry. Moreover, an immune-related prognostic model based on KRT14 was designed to enhance the prediction accuracy for the prognosis of BC patients.</div></div><div><h3>Results</h3><div>The study found that KRT14 expression was generally downregulated in BC, correlating strongly with poor prognosis. Compared to normal tissues, the methylation level of KRT14 was higher in BC tissues. Lower expression of KRT14 was linked to decreased anti-tumoral immune cells infiltration and increased immunosuppressive cells infiltration. Sensitivity to various key therapeutic drugs was lower in groups with diminished KRT14 expression. In addition, several potential anti-BC small molecule compounds were identified. The model designed in this study significantly enhanced the predictive capability for BC patients compared to predictions based solely on KRT14 expression levels.</div></div><div><h3>Conclusion</h3><div>Overall, KRT14 was closely correlated with the prognosis in BC, making it a reliable biomarker.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"180 ","pages":"Pages 55-73"},"PeriodicalIF":3.2,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143488625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}