Genes and immunity最新文献_第3页

Machine-learning and scRNA-Seq-based diagnostic and prognostic models illustrating survival and therapy response of lung adenocarcinoma 基于机器学习和 scRNA-Seq 的诊断和预后模型，说明肺腺癌的存活率和治疗反应。

IF 5 3区医学

Genes and immunity Pub Date : 2024-07-29 DOI: 10.1038/s41435-024-00289-0

Qingyu Cheng, Weidong Zhao, Xiaoyuan Song, Tengchuan Jin

{"title":"Machine-learning and scRNA-Seq-based diagnostic and prognostic models illustrating survival and therapy response of lung adenocarcinoma","authors":"Qingyu Cheng, Weidong Zhao, Xiaoyuan Song, Tengchuan Jin","doi":"10.1038/s41435-024-00289-0","DOIUrl":"10.1038/s41435-024-00289-0","url":null,"abstract":"Lung cancer is a major cause accounting for cancer-related mortalities, with lung adenocarcinoma (LUAD) being the most prevalent subtype. Given the high clinical and cellular heterogeneities of LUAD, accurate diagnosis and prognosis are crucial to avoid overdiagnosis and overtreatment. Taking full advantage of scRNA-Seq data to resolve the tumor heterogeneities, we explored the overall landscape of LUAD microenvironment. Utilizing the stage-specific tumor cell markers, we have developed highly accurate diagnostic and prognostic models with elevated sensitivity and specificity. The diagnostic model, developed through random forest algorithms with a thirteen-gene signature, achieved an accuracy of 96.4% and an AUC of 0.993. These metrics were further demonstrated by benchmarking with available models and scoring systems in independent cohorts. Concurrently, the prognostic model, formulated via Cox regression with a six-gene signature, effectively predicted overall survival, with elevated risk scores associated with increased fractions of cancer-associated fibroblasts, and higher likelihood of immune escape and T-cell exclusion. Subsequently, two nomograms were developed to predict survival and drug responses, facilitating their integration into clinical practice. Overall, this study underscores the potential of our models for efficient, rapid, and cost-effective diagnosis and prognosis of LUAD, adaptable to multiple expression profiling platforms and quantification methods.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"25 5","pages":"356-366"},"PeriodicalIF":5.0,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792302","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}

引用次数: 0

Identification of the ferroptosis‐related gene signature and the associated regulation axis in lung cancer and rheumatoid arthritis 确定肺癌和类风湿性关节炎中的铁蛋白沉积相关基因特征及相关调控轴。

IF 5 3区医学

Genes and immunity Pub Date : 2024-07-29 DOI: 10.1038/s41435-024-00287-2

Bo Cai, Yibin Huang, Dandan Liu, Yizheng You, Nuoshi Chen, Ligang Jie, Hongyan Du

{"title":"Identification of the ferroptosis‐related gene signature and the associated regulation axis in lung cancer and rheumatoid arthritis","authors":"Bo Cai, Yibin Huang, Dandan Liu, Yizheng You, Nuoshi Chen, Ligang Jie, Hongyan Du","doi":"10.1038/s41435-024-00287-2","DOIUrl":"10.1038/s41435-024-00287-2","url":null,"abstract":"Patients with Rheumatoid arthritis (RA) have an elevated risk of lung cancer compared to the healthy population. However, there are few studies on the relationship between RA and lung adenocarcinoma (LUAD), especially the mechanisms at the genetic level. In this study, we investigated the link between RA and LUAD regarding Ferroptosis-Related Genes. The RNA-seq data of RA (GSE77298 and GSE 82107) and LUAD(GSE75037) in the Gene Expression Omnibus (GEO) database were obtained. 259 ferroptosis-related genes were obtained from the website ( http://www.zhounan.org/ferrdb/ ).The differential genes obtained from the RA and LUAD datasets were intersected with ferroptosis-related genes to obtain the ferroptosis-related differentially expressed genes (FRDEGs). Next, the mRNA-miRNA network was constructed, then Gene Set Enrichment Analysis (GSEA) for target genes were performed. The CIBERSORT algorithm was used to analyze the immune infiltration. Finally, the results were validated using external datasets (GSE89408 and GSE48780) and The Cancer Genome Atlas (TCGA) dataset. We obtained FRDEGs common to LUAD and RA: FANCD2, HELLS, RRM2, G6PD, VLDLR. These five genes play important roles in the progression of RA and LUAD. They also hold great diagnostic value for both diseases. Also, we found that LUAD and RA share common signaling pathways and similar immune mechanisms.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"25 5","pages":"367-380"},"PeriodicalIF":5.0,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855280","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}

引用次数: 0

The shared role of neutrophils in ankylosing spondylitis and ulcerative colitis 中性粒细胞在强直性脊柱炎和溃疡性结肠炎中的共同作用。

IF 5 3区医学

Genes and immunity Pub Date : 2024-07-25 DOI: 10.1038/s41435-024-00286-3

Tianyou Chen, Weiming Tan, Xinli Zhan, Chenxing Zhou, Jichong Zhu, Shaofeng Wu, Boli Qin, Rongqing He, Xiaopeng Qin, Wendi Wei, Chengqian Huang, Bin Zhang, Sitan Feng, Chong Liu

{"title":"The shared role of neutrophils in ankylosing spondylitis and ulcerative colitis","authors":"Tianyou Chen, Weiming Tan, Xinli Zhan, Chenxing Zhou, Jichong Zhu, Shaofeng Wu, Boli Qin, Rongqing He, Xiaopeng Qin, Wendi Wei, Chengqian Huang, Bin Zhang, Sitan Feng, Chong Liu","doi":"10.1038/s41435-024-00286-3","DOIUrl":"10.1038/s41435-024-00286-3","url":null,"abstract":"This study aimed to analyze single-cell sequencing data to investigate immune cell interactions in ankylosing spondylitis (AS) and ulcerative colitis (UC). Vertebral bone marrow blood was collected from three AS patients for 10X single-cell sequencing. Analysis of single-cell data revealed distinct cell types in AS and UC patients. Cells significantly co-expressing immune cells (P < 0.05) were subjected to communication analysis. Overlapping genes of these co-expressing immune cells were subjected to GO and KEGG analyses. Key genes were identified using STRING and Cytoscape to assess their correlation with immune cell expression. The results showed the significance of neutrophils in both diseases (P < 0.01), with notable interactions identified through communication analysis. XBP1 emerged as a Hub gene for both diseases, with AUC values of 0.760 for AS and 0.933 for UC. Immunohistochemistry verified that the expression of XBP1 was significantly lower in the AS group and significantly greater in the UC group than in the control group (P < 0.01). This finding highlights the critical role of neutrophils in both AS and UC, suggesting the presence of shared immune response elements. The identification of XBP1 as a potential therapeutic target offers promising intervention avenues for both diseases.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"25 4","pages":"324-335"},"PeriodicalIF":5.0,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141765878","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}

引用次数: 0

Validating genetic variants in innate immunity linked to infectious events in acute myeloid leukemia post-induction chemotherapy 验证与急性髓性白血病诱导化疗后感染事件有关的先天性免疫基因变异。

IF 5 3区医学

Genes and immunity Pub Date : 2024-07-09 DOI: 10.1038/s41435-024-00285-4

Ulf Schnetzke, Mike Fischer, Christoph Röllig, André Scherag, Heidi Altmann, Friedrich Stölzel, Nael Alakel, Martin Bornhäuser, Andreas Hochhaus, Sebastian Scholl

{"title":"Validating genetic variants in innate immunity linked to infectious events in acute myeloid leukemia post-induction chemotherapy","authors":"Ulf Schnetzke, Mike Fischer, Christoph Röllig, André Scherag, Heidi Altmann, Friedrich Stölzel, Nael Alakel, Martin Bornhäuser, Andreas Hochhaus, Sebastian Scholl","doi":"10.1038/s41435-024-00285-4","DOIUrl":"10.1038/s41435-024-00285-4","url":null,"abstract":"Infectious events, such as sepsis and invasive fungal disease (IFD), pose significant risks in patients with acute myeloid leukemia (AML). Previous studies, including our own, have suggested a potential role of single nucleotide polymorphisms (SNPs) within the innate immune system in influencing individual infection susceptibility. However, many of these associations lack validation in independent cohorts. This study sought to validate the impact of 11 candidate SNPs across 6 genes (TLR2, TLR4, Dectin-1, DC-SIGN, PTX3, L-Ficolin) in an independent cohort of patients. Two cohorts with newly diagnosed AML patients receiving intensive induction chemotherapy were analyzed: a stratification cohort comprising 186 patients and a validation cohort consisting of 138 patients. Multiple SNPs in each cohort were found to be associated to infectious complications, notably the DC-SIGN SNP rs4804800 demonstrated a significant association with sepsis in both cohorts. SNPs within the PTX3 and Dectin-1 genes were linked to IFD development in one cohort each. This study represents the first validation study of candidate genes associated with infectious events in AML patients after intensive induction chemotherapy. Identifying genetic predispositions to infections could significantly impact the management of antimicrobial prophylaxis and treatment in AML patients.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"25 4","pages":"317-323"},"PeriodicalIF":5.0,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41435-024-00285-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563233","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}

引用次数: 0

SARS-CoV-2 viral persistence in lung alveolar macrophages is controlled by IFN-γ and NK cells SARS-CoV-2 病毒在肺泡巨噬细胞中的持续存在受 IFN-γ 和 NK 细胞的控制。

IF 5 3区医学

Genes and immunity Pub Date : 2024-06-26 DOI: 10.1038/s41435-024-00284-5

Emma Beaumont, Michaela Müller-Trutwin, Nicolas Huot

引用次数: 0

The ability of microRNAs to regulate the immune response in ischemia/reperfusion inflammatory pathways microRNA 在缺血/再灌注炎症途径中调节免疫反应的能力。

IF 5 3区医学

Genes and immunity Pub Date : 2024-06-22 DOI: 10.1038/s41435-024-00283-6

Peter Artimovič, Ivana Špaková, Ema Macejková, Timea Pribulová, Miroslava Rabajdová, Mária Mareková, Martina Zavacká

引用次数: 0

Correction: Getting under the skin: resident memory CD8+ T cells have a second residence in the draining lymph node 更正：深入皮下：常驻记忆 CD8+ T 细胞在引流淋巴结有第二居所。

IF 5 3区医学

Genes and immunity Pub Date : 2024-06-19 DOI: 10.1038/s41435-024-00282-7

Teresa Neuwirth, Azuah L. Gonzalez, Emilie Fisher-Gupta, Georg Stary

引用次数: 0

PARP inhibitor and immune checkpoint inhibitor have synergism efficacy in gallbladder cancer PARP抑制剂和免疫检查点抑制剂对胆囊癌有协同疗效

IF 5 3区医学

Genes and immunity Pub Date : 2024-06-12 DOI: 10.1038/s41435-024-00280-9

Yu Chen, Xudong Fan, Ruohuang Lu, Shan Zeng, Pingping Gan

{"title":"PARP inhibitor and immune checkpoint inhibitor have synergism efficacy in gallbladder cancer","authors":"Yu Chen, Xudong Fan, Ruohuang Lu, Shan Zeng, Pingping Gan","doi":"10.1038/s41435-024-00280-9","DOIUrl":"10.1038/s41435-024-00280-9","url":null,"abstract":"Gallbladder cancer (GBC) is an aggressive cancer with poor prognosis. PARP inhibitors (PARPi) target PARP enzymes and have shown efficacy in patients with breast cancer gene (BRCA) mutations. Immunotherapy, especially immune checkpoint inhibitors (ICIs), has transformed cancer treatment. However, the combined impact of PARPi and ICIs in GBC remains unclear. We present a groundbreaking case of a GBC patient with BRCA2 mutations who received combination therapy with PARPi and ICIs after failing multiple lines of treatment. Next-generation sequencing (NGS-Seq) identified BRCA gene mutations. To further investigate potential mechanisms, we developed a PARP1-BRCA1-BRCA2 pathway-related risk score (PBscore) system to evaluate the impact of PARPi on the tumor immune microenvironment via RNA-Seq data. Gene expression and functional analysis identified potential mechanisms associated with the PBscore. Experimental validation assessed the impact of the combination therapy on the tumor microenvironment using multiplexed immunofluorescence imaging and immunohistochemistry in patients with BRCA gene wild type or mutations. RNA-Seq analysis revealed correlations between PBscore, immune checkpoint levels, tumor-infiltrating immune cells (TIICs), and the cancer-immunity cycle. Multiplexed immunofluorescence imaging validated that low PBscore patients might have an active tumor microenvironment. Furthermore, upon drug resistance, we observed an upregulation of negative immune checkpoints such as CEACAM1, indicating that the tumor immune microenvironment becomes suppressed after resistance. Our study revealed that PBscore could serve as a biomarker to predict immunotherapy efficacy, offering a promising alternative for BRCA2-mutated GBC patients.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"25 4","pages":"307-316"},"PeriodicalIF":5.0,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310468","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}

引用次数: 0

Sphingomyelin-derived epacadostat nanovesicle enhances IDO1 inhibition for improved melanoma combination immunotherapy 鞘磷脂衍生的依帕卡托司他纳米囊泡可增强对 IDO1 的抑制，从而改善黑色素瘤联合免疫疗法。

IF 5 3区医学

Genes and immunity Pub Date : 2024-06-11 DOI: 10.1038/s41435-024-00281-8

Zhiren Wang, Wenpan Li, Jianqin Lu

引用次数: 0

Resolving haplotype variation and complex genetic architecture in the human immunoglobulin kappa chain locus in individuals of diverse ancestry 解析人类免疫球蛋白 kappa 链基因座中不同血统个体的单倍型变异和复杂遗传结构。

IF 5 3区医学

Genes and immunity Pub Date : 2024-06-06 DOI: 10.1038/s41435-024-00279-2

Eric Engelbrecht, Oscar L. Rodriguez, Kaitlyn Shields, Steven Schultze, David Tieri, Uddalok Jana, Gur Yaari, William D. Lees, Melissa L. Smith, Corey T. Watson

{"title":"Resolving haplotype variation and complex genetic architecture in the human immunoglobulin kappa chain locus in individuals of diverse ancestry","authors":"Eric Engelbrecht, Oscar L. Rodriguez, Kaitlyn Shields, Steven Schultze, David Tieri, Uddalok Jana, Gur Yaari, William D. Lees, Melissa L. Smith, Corey T. Watson","doi":"10.1038/s41435-024-00279-2","DOIUrl":"10.1038/s41435-024-00279-2","url":null,"abstract":"Immunoglobulins (IGs), critical components of the human immune system, are composed of heavy and light protein chains encoded at three genomic loci. The IG Kappa (IGK) chain locus consists of two large, inverted segmental duplications. The complexity of the IG loci has hindered use of standard high-throughput methods for characterizing genetic variation within these regions. To overcome these limitations, we use long-read sequencing to create haplotype-resolved IGK assemblies in an ancestrally diverse cohort (n = 36), representing the first comprehensive description of IGK haplotype variation. We identify extensive locus polymorphism, including novel single nucleotide variants (SNVs) and novel structural variants harboring functional IGKV genes. Among 47 functional IGKV genes, we identify 145 alleles, 67 of which were not previously curated. We report inter-population differences in allele frequencies for 10 IGKV genes, including alleles unique to specific populations within this dataset. We identify haplotypes carrying signatures of gene conversion that associate with SNV enrichment in the IGK distal region, and a haplotype with an inversion spanning the proximal and distal regions. These data provide a critical resource of curated genomic reference information from diverse ancestries, laying a foundation for advancing our understanding of population-level genetic variation in the IGK locus.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"25 4","pages":"297-306"},"PeriodicalIF":5.0,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41435-024-00279-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283487","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}

引用次数: 0