bioRxiv - Cancer Biology最新文献_第8页

Interactions between neutrophils and macrophages harboring gram-negative bacteria promote obesity-associated breast cancer 中性粒细胞与携带革兰氏阴性菌的巨噬细胞之间的相互作用会促进肥胖相关性乳腺癌的发生

bioRxiv - Cancer Biology Pub Date : 2024-08-09 DOI: 10.1101/2024.08.08.607253

Sina T. Takle, Sturla Magnus Grondal, Martin E. Lien, Priscilia Lianto, Wei Deng, Reidun Kristine Lillestol, Per Lonning, James B. Lorens, Stian Knappskog, Nils Halberg

引用次数: 0

Single-cell multidimensional profiling of tumor cell heterogeneity in supratentorial ependymomas 幕上脑膜瘤肿瘤细胞异质性的单细胞多维特征分析

bioRxiv - Cancer Biology Pub Date : 2024-08-09 DOI: 10.1101/2024.08.07.607066

Daeun Jeong, Sara G. Danielli, Kendra K. Maaß, David R. Ghasemi, Svenja K. Tetzlaff, Ekin Reyhan, Carlos Alberto Oliveira de Biagi-Junior, Sina Neyazi, Andrezza Nascimento, Rebecca Haase, Costanza Lo Cascio, Bernhard Englinger, Li Jiang, Cuong M. Nguyen, Alicia-Christina Baumgartner, Sophia Castellani, Jacob S. Rozowsky, Olivia A. Hack, McKenzie L. Shaw, Daniela Lotsch-Gojo, Katharina Bruckner, Stefan M. Pfister, Marcel Kool, Tomasz J. Nowakowski, Johannes Gojo, Lissa Baird, Sanda Alexandrescu, Kristian W. Pajtler, Varun Venkataramani, Mariella G. Filbin

{"title":"Single-cell multidimensional profiling of tumor cell heterogeneity in supratentorial ependymomas","authors":"Daeun Jeong, Sara G. Danielli, Kendra K. Maaß, David R. Ghasemi, Svenja K. Tetzlaff, Ekin Reyhan, Carlos Alberto Oliveira de Biagi-Junior, Sina Neyazi, Andrezza Nascimento, Rebecca Haase, Costanza Lo Cascio, Bernhard Englinger, Li Jiang, Cuong M. Nguyen, Alicia-Christina Baumgartner, Sophia Castellani, Jacob S. Rozowsky, Olivia A. Hack, McKenzie L. Shaw, Daniela Lotsch-Gojo, Katharina Bruckner, Stefan M. Pfister, Marcel Kool, Tomasz J. Nowakowski, Johannes Gojo, Lissa Baird, Sanda Alexandrescu, Kristian W. Pajtler, Varun Venkataramani, Mariella G. Filbin","doi":"10.1101/2024.08.07.607066","DOIUrl":"https://doi.org/10.1101/2024.08.07.607066","url":null,"abstract":"Supratentorial ependymomas are aggressive childhood brain cancers that retain features of neurodevelopmental cell types and segregate into molecularly and clinically distinct subgroups, suggesting different developmental roots. The developmental signatures as well as microenvironmental factors underlying aberrant cellular transformation and behavior across each supratentorial ependymoma subgroup are unknown. Here we integrated single cell- and spatial transcriptomics, as well as <em>in vitro</em> and <em>in vivo</em> live-cell imaging to define supratentorial ependymoma cell states, spatial organization, and dynamic behavior within the neural microenvironment. We find that individual tumor subgroups harbor two distinct progenitor-like cell states reminiscent of early human brain development and diverge in the extent of neuronal or ependymal differentiation. We further uncover several modes of spatial organization of these tumors, including a high order architecture influenced by mesenchymal and hypoxia signatures. Finally, we identify an unappreciated role for brain-resident cells in shifting supratentorial ependymoma cellular heterogeneity towards neuronal-like cells that co-opt immature neuronal morphology and invasion mechanisms. Collectively, these findings provide a multidimensional framework to integrate transcriptional and phenotypic characterization of tumor heterogeneity in supratentorial ependymoma and its potential clinical implications.","PeriodicalId":501233,"journal":{"name":"bioRxiv - Cancer Biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141931090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Composite impact of genome-wide APOBEC3-mediated mutations and HLA haplotype on cancer immunogenicity has a sex-biased survival impact 全基因组 APOBEC3 介导的突变和 HLA 单倍型对癌症免疫原性的综合影响具有性别差异的生存影响

bioRxiv - Cancer Biology Pub Date : 2024-08-08 DOI: 10.1101/2024.08.07.607038

Faezeh Borzooee, Alireza Heravi-Moussavi, Mani Larijani

{"title":"Composite impact of genome-wide APOBEC3-mediated mutations and HLA haplotype on cancer immunogenicity has a sex-biased survival impact","authors":"Faezeh Borzooee, Alireza Heravi-Moussavi, Mani Larijani","doi":"10.1101/2024.08.07.607038","DOIUrl":"https://doi.org/10.1101/2024.08.07.607038","url":null,"abstract":"APOBEC3A and APOBEC3B genome mutator enzymes drive tumor evolution and drug resistance. However, their mutational activity can also generate neoepitopes that activate cytotoxic T cells (CTLs). Given the high polymorphism of Class I HLA, the CTL immunopeptidome is individual-specific. We used a genome-wide immunogenicity scanning pipeline to assess how APOBEC3A/B-induced mutations affect the immunogenicity of the entire human immunopeptidome, consisting of all possible 8-11mer peptides restricted by several thousand HLA class I alleles. We evaluated several billion APOBEC3-mediated mutations for their potential to alter peptide:MHC and T cell receptor binding, either increasing or decreasing immunogenicity. We then ranked HLA alleles based on the degree to which their restricted immunopeptidome lost or gained immunogenicity when mutated by APOBEC3A or APOBEC3B. We found that HLA class I alleles vary infinitely in the proportions of their immunopeptidome whose immunogenicity is diminished vs. enhanced by APOBEC3-mediated mutations, with mutations in APOBEC3B hotspots having the greatest potential for enhancement of immunogenicity. The cumulative potential of an individual’s HLA haplotype’s immunopeptidome to gain or lose immunogenicity upon APOBEC3-mediated mutation predicts survival in APOBEC3-mutated tumors and correlates with increased CD8+ T cell activation. Thus, HLA haplotype is a prognostic marker in APOBEC3-mutated tumors.","PeriodicalId":501233,"journal":{"name":"bioRxiv - Cancer Biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141931019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deep Visual Proteomics reveals DNA replication stress as a hallmark of Signet Ring Cell Carcinoma 深度视觉蛋白质组学揭示 DNA 复制应激是印戒细胞癌的特征之一

bioRxiv - Cancer Biology Pub Date : 2024-08-08 DOI: 10.1101/2024.08.07.606985

Sonja Kabatnik, Xiang Zheng, Georgios Pappas, Sophia Steigerwald, Matthew P Padula, Matthias Mann

{"title":"Deep Visual Proteomics reveals DNA replication stress as a hallmark of Signet Ring Cell Carcinoma","authors":"Sonja Kabatnik, Xiang Zheng, Georgios Pappas, Sophia Steigerwald, Matthew P Padula, Matthias Mann","doi":"10.1101/2024.08.07.606985","DOIUrl":"https://doi.org/10.1101/2024.08.07.606985","url":null,"abstract":"Signet Ring Cell Carcinoma (SRCC) is a rare and highly malignant form of adenocarcinoma with increasing incidence and poor prognosis due to late diagnosis and limited treatment options. We employed Deep Visual Proteomics (DVP), which combines AI directed cell segmentation and classification with laser microdissection and ultra-high sensitivity mass spectrometry, for cell-type specific proteomic analysis of SRCC across the bladder, prostate, liver, and lymph nodes of a single patient. DVP identified significant alterations in DNA damage response (DDR) proteins, particularly within the ATR and mismatch repair (MMR) pathways, indicating replication stress as a crucial factor in SRCC mutagenicity. Additionally, we observed substantial enrichment of immune-related proteins, reflecting high levels of cytotoxic T lymphocyte infiltration and elevated PD-1 expression. These findings suggest that pembrolizumab immunotherapy may be more effective than conventional chemotherapy for this patient. Our results provide novel insights into the proteomic landscape of SRCC, identifying potential targets and open up for personalized therapeutic strategies in managing SRCC.","PeriodicalId":501233,"journal":{"name":"bioRxiv - Cancer Biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141931091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploit Spatially Resolved Transcriptomic Data to Infer Cellular Features from Pathology Imaging Data 利用空间分辨转录组数据从病理成像数据中推断细胞特征

bioRxiv - Cancer Biology Pub Date : 2024-08-07 DOI: 10.1101/2024.08.05.606654

Zhining Sui, Ziyi Li, Wei Sun

{"title":"Exploit Spatially Resolved Transcriptomic Data to Infer Cellular Features from Pathology Imaging Data","authors":"Zhining Sui, Ziyi Li, Wei Sun","doi":"10.1101/2024.08.05.606654","DOIUrl":"https://doi.org/10.1101/2024.08.05.606654","url":null,"abstract":"Digital pathology is a rapidly advancing field where deep learning methods can be employed to extract meaningful imaging features. However, the efficacy of training deep learning models is often hindered by the scarcity of annotated pathology images, particularly images with detailed annotations for small image patches or tiles. To overcome this challenge, we propose an innovative approach that leverages paired spatially resolved transcriptomic data to annotate pathology images. We demonstrate the feasibility of this approach and introduce a novel transfer-learning neural network model, STpath (Spatial Transcriptomics and pathology images), designed to predict cell type proportions or classify tumor microenvironments. Our findings reveal that the features from pre-trained deep learning models are associated with cell type identities in pathology image patches. Evaluating STpath using three distinct breast cancer datasets, we observe its promising performance despite the limited training data. STpath excels in samples with variable cell type proportions and high-resolution pathology images. As the influx of spatially resolved transcriptomic data continues, we anticipate ongoing updates to STpath, evolving it into an invaluable AI tool for assisting pathologists in various diagnostic tasks.","PeriodicalId":501233,"journal":{"name":"bioRxiv - Cancer Biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141931096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MUC2 Expression Modulates Immune Infiltration in Colorectal Cancer MUC2 表达调节结直肠癌中的免疫渗透

bioRxiv - Cancer Biology Pub Date : 2024-08-07 DOI: 10.1101/2024.08.06.594842

Christophe M. Raynaud, Ayesha Jabeen, Eiman I. Ahmed, Satanay Hubrack, Apryl Sanchez, Shimaa Sherif, Ahmad A Al-Shaibi, Jessica Roelands, Bernice Lo, Davide Bedognetti, Wouter Hendrickx

引用次数: 0

The PVT1, HULC, and HOTTIP expression changes due to treatment in Diffuse Large B-cell lymphoma 弥漫大 B 细胞淋巴瘤治疗引起的 PVT1、HULC 和 HOTTIP 表达变化

bioRxiv - Cancer Biology Pub Date : 2024-08-07 DOI: 10.1101/2024.08.05.606587

Milad Shahsavari, Sedigheh Arbabian, Farzaneh Hosseini, Mohamad Reza Razavi

引用次数: 0

Mutant EZH2 alters the epigenetic network and increases epigenetic heterogeneity in B cell lymphoma 突变的 EZH2 会改变 B 细胞淋巴瘤的表观遗传网络并增加其表观遗传异质性

bioRxiv - Cancer Biology Pub Date : 2024-08-07 DOI: 10.1101/2024.08.05.606629

Ofir Griess, Noa Furth, Nofar Harpaz, Nicoletta Di Bernardo, Tomer-Meir Salame, Bareket Dassa, Ioannis Karagiannidis, Yusuke Isshiki, Menachem Gross, Ari M. Melnick, Wendy Béguelin, Guy Ron, Efrat Shema

{"title":"Mutant EZH2 alters the epigenetic network and increases epigenetic heterogeneity in B cell lymphoma","authors":"Ofir Griess, Noa Furth, Nofar Harpaz, Nicoletta Di Bernardo, Tomer-Meir Salame, Bareket Dassa, Ioannis Karagiannidis, Yusuke Isshiki, Menachem Gross, Ari M. Melnick, Wendy Béguelin, Guy Ron, Efrat Shema","doi":"10.1101/2024.08.05.606629","DOIUrl":"https://doi.org/10.1101/2024.08.05.606629","url":null,"abstract":"Diffuse large B cell lymphomas and follicular lymphomas show recurrent mutations in epigenetic regulators; among these are loss-of-function mutations in KMT2D and gain-of-function mutations in EZH2. To systematically explore the effects of these mutations on the wiring of the epigenetic network, we applied a single-cell approach to probe a wide array of histone modifications. We show that mutant-EZH2 elicits extensive effects on the epigenome of lymphomas, beyond alterations to H3K27 methylations, and is dominant over KMT2D mutations. Utilizing the single-cell data, we present computational methods to measure epigenetic heterogeneity. We identify an unexpected characteristic of mutant-EZH2, but not KMT2D, in increasing heterogeneity, shedding light on a novel oncogenic mechanism mediated by this mutation. Finally, we present tools to reconstruct known interactions within the epigenetic network, as well as reveal potential novel cross talk between various modifications, validated by functional perturbations. Our work highlights novel roles for mutant-EZH2 in lymphomagenesis and establishes new concepts for measuring epigenetic heterogeneity and intra-chromatin connectivity in cancer cells.","PeriodicalId":501233,"journal":{"name":"bioRxiv - Cancer Biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141931040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Clonal evolutionary analysis reveals patterns of malignant transformation in pancreatic cancer from Intraductal Papillary Mucinous IPMN Neoplasms (IPMN) 克隆进化分析揭示了胰腺癌从导管内乳头状粘液性 IPMN 肿瘤（IPMN）恶性转化的模式

bioRxiv - Cancer Biology Pub Date : 2024-08-07 DOI: 10.1101/2024.08.02.606217

Antonio Pea, Xiaotong He, Rosie Upstill-Goddard, Claudio Luchini, Leonor Patricia Schubert Santana, Stephan Dreyer, Fraser Duthie, Nigel B. Jamieson, Colin J. McKay, Euan J. Dickson, Alessandra Pulvirenti, Selma Rebus, Genomics Innovation Alliance, Scottish Genome Partnership, Paola Piccoli, Nicola Sperandio, Rita T. Lawlor, Michele Milella, Fieke E. M. Froeling, Roberto Salvia, Aldo Scarpa, Andrew V. Bainkin, David C. Wedge, David K. Chang

{"title":"Clonal evolutionary analysis reveals patterns of malignant transformation in pancreatic cancer from Intraductal Papillary Mucinous IPMN Neoplasms (IPMN)","authors":"Antonio Pea, Xiaotong He, Rosie Upstill-Goddard, Claudio Luchini, Leonor Patricia Schubert Santana, Stephan Dreyer, Fraser Duthie, Nigel B. Jamieson, Colin J. McKay, Euan J. Dickson, Alessandra Pulvirenti, Selma Rebus, Genomics Innovation Alliance, Scottish Genome Partnership, Paola Piccoli, Nicola Sperandio, Rita T. Lawlor, Michele Milella, Fieke E. M. Froeling, Roberto Salvia, Aldo Scarpa, Andrew V. Bainkin, David C. Wedge, David K. Chang","doi":"10.1101/2024.08.02.606217","DOIUrl":"https://doi.org/10.1101/2024.08.02.606217","url":null,"abstract":"Intraductal papillary mucinous neoplasms (IPMNs) are critical precursors to pancreatic ductal adenocarcinoma (PDAC), a highly lethal cancer due to late detection and rapid progression. Using multi-region whole-genome and transcriptome sequencing, we traced the evolution of PDAC from IPMN, constructing detailed phylogenetic trees to provide insights into subclonal architectures and progression pathways. Our analysis identified two distinct evolutionary trajectories: one driven by a single ancestral clone, and another involving multiple independent ancestral clones, potentially influencing the timing and nature of PDAC onset. We further explored the roles of mutational signatures and structural variants (SVs) in promoting clonal evolution. Complementing these genomic findings, our transcriptomic analysis revealed unique gene expression profiles and variations in the immune landscape, correlating with the different progression stages from IPMN to PDAC. These insights reveal the complex molecular dynamics of IPMN progression to PDAC, highlighting the need to refine early detection and treatment strategies.","PeriodicalId":501233,"journal":{"name":"bioRxiv - Cancer Biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141931035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Role of SCAL1 in Modulating Oxidative Stress, Cancer Stemness, Apoptotic Resistance in Tumorigenic Differentiation of Cigarette Smoke-Exposed BEAS-2B Cells SCAL1 在调节氧化应激、癌症干性和烟雾暴露 BEAS-2B 细胞致瘤分化过程中的凋亡抵抗中的作用

bioRxiv - Cancer Biology Pub Date : 2024-08-07 DOI: 10.1101/2024.08.05.606632

Debmalya Sengupta, Souradeep Banerjee, Mainak Sengupta

{"title":"Role of SCAL1 in Modulating Oxidative Stress, Cancer Stemness, Apoptotic Resistance in Tumorigenic Differentiation of Cigarette Smoke-Exposed BEAS-2B Cells","authors":"Debmalya Sengupta, Souradeep Banerjee, Mainak Sengupta","doi":"10.1101/2024.08.05.606632","DOIUrl":"https://doi.org/10.1101/2024.08.05.606632","url":null,"abstract":"The smoke and cancer-associated lncRNA 1 (SCAL1) is an emergent biomarker in lung cancer. However, the precise role of SCAL1 as a mediator of tobacco smoke-induced lung carcinogenesis remains unclear. BEAS-2B cells were cultured and exposed to 20% cigarette smoke extract (CSE), followed by quantification of SCAL1. We evaluated the impact of SCAL1 on cell viability, ROS mitigation, cancer stemness, tumorigenic differentiation, cellular invasiveness, and apoptosis for different CSE incubation time points through SCAL1 expressional modulation using SCAL1-specific siRNAs and scrambled controls. We observed an upregulation of SCAL1 in cells exposed to CSE for 2, 4, and 6 hours, with the highest expression observed at 6 hours (p<0.001). Exposure of BEAS-2B cells to CSE showed the formation of focal adhesions and stress fibers resembling tunneling nanotubes. Intracellular ROS levels significantly increased upon CSE exposure compared to control cells (p<0.05). We found increased levels of anti-apoptotic and cancer stem (CSC) cell markers like BCL2, ALDH1A1, CD133, CD44, and TCTP and decreased levels of TP53 in CSE-exposed cells. Knockdown of SCAL1 using siRNA transfection reversed these effects at all time points. Additionally, we observed a significant decrease in the number of spheroid colonies in siSCAL1 (+) cells compared to siSCAL1 (-) cells (p<0.01) exposed to CSE. SCAL1 is pivotal in mediating cellular responses to cigarette smoke, leading to tumorigenic differentiation of BEAS-2B cells. Understanding the mechanisms could provide valuable insights into lung cancer pathogenesis and therapeutic approaches.","PeriodicalId":501233,"journal":{"name":"bioRxiv - Cancer Biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141931094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0