Biomarker Research最新文献

{"title":"Immune escape of multiple myeloma cells results from low miR29b and the ensuing epigenetic silencing of proteasome genes","authors":"Patrizia Leone, E. Malerba, M. Prete, A. Solimando, Giorgio Alberto Croci, P. Ditonno, Marco Tucci, N. Susca, Afshin Derakhshani, Antoine Dufour, V. De Re, N. Silvestris, V. Racanelli","doi":"10.1186/s40364-024-00592-y","DOIUrl":"https://doi.org/10.1186/s40364-024-00592-y","url":null,"abstract":"","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":11.1,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140669075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNAs predict early complications of autologous hematopoietic stem cell transplantation","authors":"D. Mikulski, M. Nowicki, I. Dróżdż, E. Perdas, Piotr Strzałka, K; Kościelny, M. Misiewicz, K. Stawiski, Agnieszka Wierzbowska, Wojciech Fendler","doi":"10.1186/s40364-024-00585-x","DOIUrl":"https://doi.org/10.1186/s40364-024-00585-x","url":null,"abstract":"","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":11.1,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140671522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipid metabolism in tumor-infiltrating regulatory T cells: perspective to precision immunotherapy","authors":"Yukai Shan, Tianao Xie, Yuchao Sun, Ziyi Lu, Win Topatana, Sarun Juengpanich, Tianen Chen, Yina Han, Jiasheng Cao, Jiahao Hu, Shijie Li, Xiujun Cai, Mingyu Chen","doi":"10.1186/s40364-024-00588-8","DOIUrl":"https://doi.org/10.1186/s40364-024-00588-8","url":null,"abstract":"Regulatory T cells (Tregs) are essential to the negative regulation of the immune system, as they avoid excessive inflammation and mediate tumor development. The abundance of Tregs in tumor tissues suggests that Tregs may be eliminated or functionally inhibited to stimulate antitumor immunity. However, immunotherapy targeting Tregs has been severely hampered by autoimmune diseases due to the systemic elimination of Tregs. Recently, emerging studies have shown that metabolic regulation can specifically target tumor-infiltrating immune cells, and lipid accumulation in TME is associated with immunosuppression. Nevertheless, how Tregs actively regulate metabolic reprogramming to outcompete effector T cells (Teffs), and how lipid metabolic reprogramming contributes to the immunomodulatory capacity of Tregs have not been fully discussed. This review will discuss the physiological processes by which lipid accumulation confers a metabolic advantage to tumor-infiltrating Tregs (TI-Tregs) and amplifies their immunosuppressive functions. Furthermore, we will provide a summary of the driving effects of various metabolic regulators on the metabolic reprogramming of Tregs. Finally, we propose that targeting the lipid metabolism of TI-Tregs could be efficacious either alone or in conjunction with immune checkpoint therapy.","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":11.1,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140635274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lung cancer cell-intrinsic IL-15 promotes cell migration and sensitizes murine lung tumors to anti-PD-L1 therapy","authors":"Shaojie Hu, Kelin Meng, Tianlai Wang, Rirong Qu, Boyu Wang, Yu Xi, Taiyan Yu, Zhiwei Yuan, Zihao Cai, Yitao Tian, Chenxi Zeng, Xue Wang, Wenbin Zou, Xiangning Fu, Lequn Li","doi":"10.1186/s40364-024-00586-w","DOIUrl":"https://doi.org/10.1186/s40364-024-00586-w","url":null,"abstract":"IL-15 plays a vital role in enhancing NK cell- and T-cell-mediated antitumor immune responses; however, the direct effect of IL-15 on tumor cells has not been fully elucidated. Herein, we investigated the effect of IL-15 on lung adenocarcinoma cells. Silencing and overexpression techniques were used to modify endogenous IL-15 expression in tumor cells. Transwell assays were used to assess tumor cell migration and invasion; a live-cell analysis system was used to evaluate cell motility; cellular morphological changes were quantified by confocal fluorescence microscopy; the molecular mechanisms underlying the effect of IL-15 on tumor cells were analyzed by western blotting; and RhoA and Cdc42 activities were evaluated by a pulldown assay. NCG and C57BL/6 mouse models were used to evaluate the functions of IL-15 in vivo. Cancer cell-intrinsic IL-15 promoted cell motility and migration in vitro and metastasis in vivo via activation of the AKT-mTORC1 pathway; however, exogenous IL-15 inhibited cell motility and migration via suppression of the RhoA-MLC2 axis. Mechanistic analysis revealed that both the intracellular and extracellular IL-15-mediated effects required the expression of IL-15Rα by tumor cells. Detailed analyses revealed that the IL-2/IL-15Rβ and IL-2Rγ chains were undetected in the complex formed by intracellular IL-15 and IL-15Rα. However, when exogenous IL-15 engaged tumor cells, a complex containing the IL-15Rα, IL-2/IL-15Rβ, and IL-2Rγ chains was formed, indicating that the differential actions of intracellular and extracellular IL-15 on tumor cells might be caused by their distinctive modes of IL-15 receptor engagement. Using a Lewis lung carcinoma (LLC) metastasis model, we showed that although IL-15 overexpression facilitated the lung metastasis of LLC cells, IL-15-overexpressing LLC tumors were more sensitive to anti-PD-L1 therapy than were IL-15-wild-type LLC tumors via an enhanced antitumor immune response, as evidenced by their increased CD8+ T-cell infiltration compared to that of their counterparts. Cancer cell-intrinsic IL-15 and exogenous IL-15 differentially regulate cell motility and migration. Thus, cancer cell-intrinsic IL-15 acts as a double-edged sword in tumor progression. Additionally, high levels of IL-15 expressed by tumor cells might improve the responsiveness of tumors to immunotherapies.","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":11.1,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140630991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global research hotspots, development trends and prospect discoveries of phase separation in cancer: a decade-long informatics investigation","authors":"Song-Bin Guo, Xue-Zhao Feng, Wei-Juan Huang, Zhen-Zhong Zhou, Xiao-Peng Tian","doi":"10.1186/s40364-024-00587-9","DOIUrl":"https://doi.org/10.1186/s40364-024-00587-9","url":null,"abstract":"Liquid-liquid phase separation (LLPS) is a complex and subtle phenomenon whose formation and regulation take essential roles in cancer initiation, growth, progression, invasion, and metastasis. This domain holds a wealth of underutilized unstructured data that needs further excavation for potentially valuable information. Therefore, we retrospectively analyzed the global scientific knowledge in the field over the last decade by using informatics methods (such as hierarchical clustering, regression statistics, hotspot burst, and Walktrap algorithm analysis). Over the past decade, this area enjoyed a favorable development trend (Annual Growth Rate: 34.98%) and global collaboration (International Co-authorship: 27.31%). Through unsupervised hierarchical clustering based on machine learning, the global research hotspots were divided into five dominant research clusters: Cluster 1 (Effects and Mechanisms of Phase Separation in Drug Delivery), Cluster 2 (Phase Separation in Gene Expression Regulation), Cluster 3 (Phase Separation in RNA-Protein Interaction), Cluster 4 (Reference Value of Phase Separation in Neurodegenerative Diseases for Cancer Research), and Cluster 5 (Roles and Mechanisms of Phase Separation). And further time-series analysis revealed that Cluster 5 is the emerging research cluster. In addition, results from the regression curve and hotspot burst analysis point in unison to super-enhancer (a=0.5515, R2=0.6586, p=0.0044) and stress granule (a=0.8000, R2=0.6000, p=0.0085) as the most potential star molecule in this field. More interestingly, the Random-Walk-Strategy-based Walktrap algorithm further revealed that “phase separation, cancer, transcription, super-enhancer, epigenetics”(Relevance Percentage[RP]=100%, Development Percentage[DP]=29.2%), “stress granule, immunotherapy, tumor microenvironment, RNA binding protein”(RP=79.2%, DP=33.3%) and “nanoparticle, apoptosis”(RP=70.8%, DP=25.0%) are closely associated with this field, but are still under-developed and worthy of further exploration. In conclusion, this study profiled the global scientific landscape, discovered a crucial emerging research cluster, identified several pivotal research molecules, and predicted several crucial but still under-developed directions that deserve further research, providing an important reference value for subsequent basic and clinical research of phase separation in cancer.","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":11.1,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140563433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metallothionein-3 is a multifunctional driver that modulates the development of sorafenib-resistant phenotype in hepatocellular carcinoma cells","authors":"Miguel Angel Merlos Rodrigo, Hana Michalkova, Ana Maria Jimenez Jimenez, Frantisek Petrlak, Tomas Do, Ladislav Sivak, Yazan Haddad, Petra Kubickova, Vivian de los Rios, J. Ignacio Casal, Marina Serrano-Macia, Teresa C. Delgado, Loreto Boix, Jordi Bruix, Maria L. Martinez Chantar, Vojtech Adam, Zbynek Heger","doi":"10.1186/s40364-024-00584-y","DOIUrl":"https://doi.org/10.1186/s40364-024-00584-y","url":null,"abstract":"Metallothionein-3 (hMT3) is a structurally unique member of the metallothioneins family of low-mass cysteine-rich proteins. hMT3 has poorly characterized functions, and its importance for hepatocellular carcinoma (HCC) cells has not yet been elucidated. Therefore, we investigated the molecular mechanisms driven by hMT3 with a special emphasis on susceptibility to sorafenib. Intrinsically sorafenib-resistant (BCLC-3) and sensitive (Huh7) cells with or without up-regulated hMT3 were examined using cDNA microarray and methods aimed at mitochondrial flux, oxidative status, cell death, and cell cycle. In addition, in ovo/ex ovo chick chorioallantoic membrane (CAM) assays were conducted to determine a role of hMT3 in resistance to sorafenib and associated cancer hallmarks, such as angiogenesis and metastastic spread. Molecular aspects of hMT3-mediated induction of sorafenib-resistant phenotype were delineated using mass-spectrometry-based proteomics. The phenotype of sensitive HCC cells can be remodeled into sorafenib-resistant one via up-regulation of hMT3. hMT3 has a profound effect on mitochondrial respiration, glycolysis, and redox homeostasis. Proteomic analyses revealed a number of hMT3-affected biological pathways, including exocytosis, glycolysis, apoptosis, angiogenesis, and cellular stress, which drive resistance to sorafenib. hMT3 acts as a multifunctional driver capable of inducing sorafenib-resistant phenotype of HCC cells. Our data suggest that hMT3 and related pathways could serve as possible druggable targets to improve therapeutic outcomes in patients with sorafenib-resistant HCC.","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":11.1,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140564118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Combined TP53 status in tumor-free resection margins and circulating microRNA profiling predicts the risk of locoregional recurrence in head and neck cancer.","authors":"Federica Ganci, Matteo Allegretti, Carlotta Frascolla, Francesca Spinella, Francesca Rollo, Andrea Sacconi, Valentina De Pascale, Alina Catalina Palcau, Valentina Manciocco, Mariavittoria Vescovo, Ettore Cotroneo, Francesca Blandino, Maria Benevolo, Renato Covello, Paola Muti, Sabrina Strano, Antonello Vidiri, Giulia Fontemaggi, Raul Pellini, Giovanni Blandino","doi":"10.1186/s40364-024-00582-0","DOIUrl":"10.1186/s40364-024-00582-0","url":null,"abstract":"","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":11.1,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10964511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140295310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing adenovirus in cancer immunotherapy: evoking cellular immunity and targeting delivery in cell-specific manner.","authors":"Miao Zeng, Wei Zhang, Yisheng Li, Li Yu","doi":"10.1186/s40364-024-00581-1","DOIUrl":"10.1186/s40364-024-00581-1","url":null,"abstract":"<p><p>Recombinant adenovirus (rAd) regimens, including replication-competent oncolytic adenovirus (OAV) and replication-deficient adenovirus, have been identified as potential cancer therapeutics. OAV presents advantages such as selective replication, oncolytic efficacy, and tumor microenvironment (TME) remodeling. In this perspective, the principles and advancements in developing OAV toolkits are reviewed. The burgeoning rAd may dictate efficacy of conventional cancer therapies as well as cancer immunotherapies, including cancer vaccines, synergy with adoptive cell therapy (ACT), and TME reshaping. Concurrently, we explored the potential of rAd hitchhiking to adoptive immune cells or stem cells, highlighting how this approach facilitates synergistic interactions between rAd and cellular therapeutics at tumor sites. Results from preclinical and clinical trials in which immune and stem cells were infected with rAd have been used to address significant oncological challenges, such as postsurgical residual tumor tissue and metastatic tissue. Briefly, rAd can eradicate tumors through various mechanisms, resulting from tumor immunogenicity, reprogramming of the TME, enhancement of cellular immunity, and effective tumor targeting. In this context, we argue that rAd holds immense potential for enhancing cellular immunity and synergistically improving antitumor effects in combination with novel cancer immunotherapies.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":11.1,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10962185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140289652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic and immunomodulatory potentials of mesenchymal stromal/stem cells and immune checkpoints related molecules.","authors":"Ali Hazrati, Kosar Malekpour, Hossein Khorramdelazad, Samira Rajaei, Seyed Mahmoud Hashemi","doi":"10.1186/s40364-024-00580-2","DOIUrl":"10.1186/s40364-024-00580-2","url":null,"abstract":"<p><p>Mesenchymal stromal/stem cells (MSCs) are used in many studies due to their therapeutic potential, including their differentiative ability and immunomodulatory properties. These cells perform their therapeutic functions by using various mechanisms, such as the production of anti-inflammatory cytokines, growth factors, direct cell-to-cell contact, extracellular vesicles (EVs) production, and mitochondrial transfer. However, mechanisms related to immune checkpoints (ICPs) and their effect on the immunomodulatory ability of MSCs are less discussed. The main function of ICPs is to prevent the initiation of unwanted responses and to regulate the immune system responses to maintain the homeostasis of these responses. ICPs are produced by various types of immune system regulatory cells, and defects in their expression and function may be associated with excessive responses that can ultimately lead to autoimmunity. Also, by expressing different types of ICPs and their ligands (ICPLs), tumor cells prevent the formation and durability of immune responses, which leads to tumors' immune escape. ICPs and ICPLs can be produced by MSCs and affect immune cell responses both through their secretion into the microenvironment or direct cell-to-cell interaction. Pre-treatment of MSCs in inflammatory conditions leads to an increase in their therapeutic potential. In addition to the effect that inflammatory environments have on the production of anti-inflammatory cytokines by MSCs, they can increase the expression of various types of ICPLs. In this review, we discuss different types of ICPLs and ICPs expressed by MSCs and their effect on their immunomodulatory and therapeutic potential.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10958918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140186272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"STAT3-mediated up-regulation of DAB2 via SRC-YAP1 signaling axis promotes Helicobacter pylori-driven gastric tumorigenesis.","authors":"Yantao Duan, Pengfei Kong, Mingzhu Huang, Yonghao Yan, Yi Dou, Binhao Huang, Jing Guo, Wei Kang, Caixia Zhu, Yuyan Wang, Donglei Zhou, Qiliang Cai, Dazhi Xu","doi":"10.1186/s40364-024-00577-x","DOIUrl":"10.1186/s40364-024-00577-x","url":null,"abstract":"<p><strong>Background: </strong>Helicobacter pylori (H pylori) infection is the primary cause of gastric cancer (GC). The role of Disabled-2 (DAB2) in GC remains largely unclear. This study aimed to investigate the role of DAB2 in H pylori-mediated gastric tumorigenesis.</p><p><strong>Methods: </strong>We screened various datasets of GC to analyze DAB2 expression and cell signaling pathways. DAB2 expression was assessed in human GC tissue microarrays. H pylori infection in vivo and in vitro models were further explored. Immunostaining, immunofluorescence, chromatin immunoprecipitation, co-immunoprecipitation, Western blot, quantitative polymerase chain reaction, and luciferase reporter assays were performed in the current study.</p><p><strong>Results: </strong>The bioinformatic analysis verified that DAB2 was 1 of the 8 genes contributed to tumorigenesis and associated with poor prognosis in GC. The median overall survival and disease-free survival rates in DAB2^high group were significantly less than those in DAB2^low group. These findings demonstrated that H pylori transcriptionally activated DAB2 expression via signal transducer and activator of transcription 3 (STAT3)-dependent pathway. By bioinformatics analysis and knockdown or overexpression of DAB2, we found that DAB2 upregulated Yes-associated protein 1 (YAP1) transcriptional activity. Mechanistically, DAB2 served as a scaffold protein for integrin beta 3 (ITGB3) and SRC proto-oncogene non-receptor tyrosine kinase (SRC), facilitated the phosphorylation of SRC, promoted the small GTPase ras homolog family member A (RHOA) activation and phosphorylation of YAP1, and ultimately enhanced the YAP1 transcriptional activity.</p><p><strong>Conclusions: </strong>Altogether, these findings indicated that DAB2 is a key mediator in STAT3-regulated translation of YAP1 and plays crucial roles in H pylori-mediated GC development. DAB2 might serve as a novel therapeutic target for GC.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":11.1,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10935867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140121334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}