Journal of Experimental & Clinical Cancer Research最新文献

{"title":"Detecting actionable mutations from matched plasma-based versus tissue next-generation sequencing in advanced non-small cell lung cancer: a retrospective single centre analysis on site.","authors":"Christophe Bontoux, Caroline Lacoux, Jonathan Benzaquen, Jacques Boutros, Guylène Rignol, Elodie Long-Mira, Sandra Lassalle, Maryline Allegra, Doriane Bohly, Mathieu Garcia, Christelle Bonnetaud, Olivier Bordone, Jean-Marc Félix, Virginie Lespinet-Fabre, Virginie Tanga, Charles-Hugo Marquette, Valérie Taly, Aurélia Baurès, Simon Heeke, Marius Ilié, Véronique Hofman, Paul Hofman","doi":"10.1186/s13046-025-03480-x","DOIUrl":"10.1186/s13046-025-03480-x","url":null,"abstract":"<p><strong>Background: </strong>Liquid biopsies (LB) are used increasingly to detect actionable mutations in patients newly diagnosed with advanced non-small cell lung cancer (aNSCLC), though tissue biopsies (TB) still remain the gold standard. The value of systematically combining LB and TB next-generation sequencing (NGS) for genomic profiling in these patients remains controversial.</p><p><strong>Methods: </strong>This single-centre retrospective study included 102 matched TB and LB samples collected from aNSCLC patients at diagnosis. Four circulating free DNA (cfDNA)-based NGS assays (1-4) were compared on site for performance and concordance with TB to detect ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) I/II. Additionally, cfDNA droplet digital PCR methylation (ddPCR-met) testing estimated the tumour fraction to refine the interpretation of wild-type (WT) results.</p><p><strong>Results: </strong>Out of 102 patients, 13% had stage IIIB disease, and 11% presented with brain-only metastases. Adenocarcinoma was the predominant subtype (84%). Ninety LB samples yielded interpretable results across the four assays. Positive percent agreement with TB ranged from 56% (assay 2) to 79% (assay 4), with high concordance, particularly for single-nucleotide variants (SNVs). Hybrid capture-based assays (3 and 4) detected eight and seven gene fusions, respectively, while amplicon-based assays (1 and 2) detected only two each. Assay 3 only identified 12 MET amplifications, five of which were confirmed by fluorescence in situ hybridisation (FISH) but were missed by TB-based NGS. Five out of six negative cfDNA samples with ddPCR-met testing were WT across all assays. The plasma-first approach added incremental value, up to 21% (assay 3). Amplicon-based assays were faster and required less input of DNA for analysis. Patients with stage IIIB or brain-only metastases were significantly more likely to have negative/low levels of cfDNA ddPCR-met.</p><p><strong>Conclusions: </strong>LB-based NGS demonstrated high concordance with TB in newly diagnosed aNSCLC, particularly for detection of SNV. Hybrid capture assays showed superior performance in identifying gene fusions and MET amplifications. The incremental value of a plasma-first strategy was limited in this real-life study. Thus, LB-based NGS on site should be seen as a complementary tool to TB-based NGS or an alternative when tissue samples are unavailable. Additionally, cfDNA methylation analysis enhances diagnostic accuracy in specific cases.</p>","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"44 1","pages":"229"},"PeriodicalIF":12.8,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12326616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144790607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CSRP2 promotes the glioblastoma mesenchymal phenotype via p130Cas-mediated NF-κB and MAPK pathways.","authors":"Jiawei He, Liang Zhang, Hao Xu, Chengtian Gao, Wentao Zhao, Bingchang Zhang, Wanhong Han, Wenpeng Zhao, Guowei Tan, Sifang Chen, Ping Zhong, Zhe Shen, Jian Meng, Ziqian Tang, Hanwen Lu, Xin Gao, Zhangyu Li, Wenhua Li, Jianyao Mao, Bosen Liu, Yun-Wu Zhang, Zhanxiang Wang","doi":"10.1186/s13046-025-03484-7","DOIUrl":"10.1186/s13046-025-03484-7","url":null,"abstract":"<p><strong>Background: </strong>Cysteine-rich protein 2 (CSRP2) plays a role in a variety of biological processes including cell proliferation and differentiation. However, whether and how CSRP2 participates in the malignancy of glioblastoma multiforme (GBM), including its proneural-to-mesenchymal transition (PMT), remains unclear.</p><p><strong>Methods: </strong>CSRP2 expression in low-grade and high-grade gliomas was analyzed, and survival analyses were performed in patients with gliomas with high and low CSRP2 expression in various tumor databases. Quantitative real-time PCR (qRT-PCR) and western blotting (WB) were used to detect the expression of CSRP2 in GBM and control brain tissues. CSRP2 function in GBM was determined by a series of functional tests in vitro and in vivo. WB, co-immunoprecipitation (co-IP) and immunofluorescence were used to determine the relation between CSRP2 and p130Cas. Mechanisms of CSRP2 involvement in GBM progression were analyzed with gene set enrichment analysis and KEGG enrichment analysis in available databases. WB was used to determine the relation between CSRP2 and PMT markers, NF-κB and MAPK signaling-related proteins, and apoptosis-related proteins. Microscale thermophoresis assay was used to analyze whether mitoxantrone (MTO) and CSRP2 could bind. MTO function was determined by a series of functional tests in vitro, while the relation between MTO and PMT markers, NF-κB and MAPK signaling-related proteins, and apoptosis-related proteins was analyzed by WB in GBM cell lines stably overexpressing CSRP2.</p><p><strong>Results: </strong>We found that CSRP2 expression significantly increased in GBM, especially mesenchymal GBM, and that glioma patients with high CSRP2 expression possibly had poor prognosis. CSRP2 overexpression in GBM cells promoted proliferation, colony formation, migration, invasion, temozolomide resistance, and PMT in vitro and tumor formation in vivo. While knockdown of CSRP2 had the opposite effects. Mechanistically, we revealed that CSRP2 interacted with p130Cas, thereby regulating the NF-κB and the MAPK signaling pathways. CSRP2 overexpression and knockdown increased and decreased p130Cas levels and NF-κB and MAPK activities, respectively. Both p130Cas downregulation and NF-κB inhibition reversed the elevated PMT and NF-κB and MAPK activities resulted from CSRP2 overexpression. Finally, we identified that MTO bound CSRP2 and inhibited the malignant effects of CSRP2 overexpression on GBM cells.</p><p><strong>Conclusions: </strong>Our findings demonstrate that CSRP2 promotes GBM malignancy including PMT and temozolomide resistance through activating p130Cas-mediated NF-κB and MAPK signaling pathways. Inhibiting CSRP2 function, including using MTO, may become a novel therapeutic approach for GBM.</p>","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"44 1","pages":"228"},"PeriodicalIF":12.8,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12323131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144790606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting tumor-associated macrophages to overcome immune checkpoint inhibitor resistance in hepatocellular carcinoma.","authors":"Fen Liu, Xianying Li, Yiming Zhang, Shan Ge, Zhan Shi, Qingbin Liu, Shulong Jiang","doi":"10.1186/s13046-025-03490-9","DOIUrl":"10.1186/s13046-025-03490-9","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) remains a critical global health concern, particularly in regions with high endemicity of hepatitis B, hepatitis C, and non-alcoholic fatty liver disease. Immunotherapy, particularly immune checkpoint inhibitors (ICIs), has emerged as a promising therapeutic strategy for advanced HCC. Despite encouraging results, primary and acquired resistance to ICIs continues to pose significant challenges in clinical practice. Recent research has identified tumor-associated macrophages (TAMs) as key contributors to immune evasion and ICI resistance in HCC, primarily through polarization to the M2 phenotype. M2-polarized TAMs secrete a range of immunosuppressive cytokines that inhibit T cell activation and promote tumor progression through processes such as angiogenesis and epithelial-mesenchymal transition. These mechanisms compromise the efficacy of ICIs and facilitate tumor expansion and metastasis. This review summarizes the role of TAM-related signaling pathways in driving immune evasion and ICI resistance in HCC, with particular emphasis on the contribution of TAM surface receptors and chemokines in immune suppression. Additionally, the review highlights emerging insights into TAM metabolic reprogramming and transcriptional regulation, which have been closely linked to ICI resistance. Furthermore, we explore promising therapeutic strategies targeting TAMs and their associated signaling pathways to enhance ICI efficacy in HCC. Integrating these novel approaches could potentially overcome TAM-driven immune evasion and ICI resistance, boosting the efficacy of immunotherapy and improving patient prognosis in HCC.</p>","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"44 1","pages":"227"},"PeriodicalIF":12.8,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12323087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144790608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repurposed clindamycin suppresses pyroptosis in tumor-associated macrophages through Inhibition of caspase-1.","authors":"Adrian Weich, Johannes Berges, Cindy Flamann, Katrin Bitterer, Krishna Pal Singh, David Chambers, Christopher Lischer, Xin Lai, Olaf Wolkenhauer, Carola Berking, Gerhard Krönke, Shailendra Gupta, Heiko Bruns, Julio Vera, Research Group Macrophages","doi":"10.1186/s13046-025-03478-5","DOIUrl":"10.1186/s13046-025-03478-5","url":null,"abstract":"<p><strong>Background: </strong>The metastatic microenvironment is often rich in tumor-associated macrophages (TAMs). In uveal melanoma (UM), high levels of TAMs positively correlate with tumor progression and poorer prognosis. We hypothesize that the immunomodulation of TAMs can remodel the UM tumor microenvironment and make it more susceptible to therapeutic interventions.</p><p><strong>Methods: </strong>In our work, we designed a novel computational pipeline that combines single-cell transcriptomics data, network analysis, multicriteria decision techniques, and pharmacophore-based docking simulations to select molecular targets and matching repurposable drugs for TAM immunomodulation. The method generates a ranking of drug-target interactions, the most promising of which are channeled towards experimental validation.</p><p><strong>Results: </strong>To identify potential immunomodulatory targets, we created a network-based representation of the TAM interactome and extracted a regulatory core conditioned on UM expression data. Further, we selected 13 genes from this core (NLRP3, HMOX1, CASP1, GSTP1, NAMPT, HSP90AA1, B2M, ISG15, LTA4H, PTGS2, CXCL2, PLAUR, ZFP36, TANK) for pharmacophore-based virtual screening of FDA-approved compounds, followed by flexible molecular docking. Based on the ranked docking results, we chose the interaction between caspase-1 and clindamycin for experimental validation. Functional studies on macrophages confirmed that clindamycin inhibits caspase-1 activity and thereby inflammasome activation, leading to a decrease in IL-1β, IL-18, and gasdermin D cleavage products as well as a reduction in pyroptotic cell death. This clindamycin-mediated inhibition of caspase-1 was also observable in TAMs derived from the bone marrow of multiple myeloma patients.</p><p><strong>Conclusions: </strong>Our computational workflow for drug repurposing identified clindamycin as an efficacious inhibitor of caspase-1 that suppresses inflammasome activity and pyroptosis in vitro in TAMs.</p>","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"44 1","pages":"225"},"PeriodicalIF":12.8,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12320367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144785842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Inhibition of autophagy enhances the antitumor efficacy of T/CAR T cell against neuroblastoma.","authors":"Francesca De Mitri, Manuela Giansanti, Ombretta Melaiu, Dorothee Haas, Stefan Ebert, Nicola Tumino, Elisabetta Vulpis, Francesca Gatto, Beatrice Martuscelli, Manuela Antonioli, Elisabetta Sangiuliano, Simona Caruso, Marco Scarsella, Cristiano De Stefanis, Veronica Marabitti, Silvia Campello, Doriana Fruci, Paola Vacca, Ignazio Caruana, Francesca Nazio","doi":"10.1186/s13046-025-03492-7","DOIUrl":"10.1186/s13046-025-03492-7","url":null,"abstract":"","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"44 1","pages":"226"},"PeriodicalIF":12.8,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12323145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144785841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sensitive detection of minimal residual disease and immunotherapy targets by multi-modal bone marrow analysis in high-risk neuroblastoma - a multi-center study.","authors":"Nina U Gelineau, Eva Bozsaky, Lieke M J van Zogchel, Fikret Rifatbegovic, Daria Lazic, Andrea Ziegler, Ahmad Javadi, Lily Zappeij-Kannegieter, Ulrike Pötschger, Marta Fiocco, Peter F Ambros, Inge M Ambros, Bernd Bodenmiller, Ellen C van der Schoot, Ruth Ladenstein, Marie Bernkopf, Godelieve A M Tytgat, Sabine Taschner-Mandl","doi":"10.1186/s13046-025-03481-w","DOIUrl":"10.1186/s13046-025-03481-w","url":null,"abstract":"<p><strong>Background: </strong>Bone marrow dissemination of tumor cells, common in various cancers, including neuroblastoma, is associated with poor outcome, necessitating sensitive detection methods for bone marrow minimal residual disease (MRD) and offer detection of biomarkers for therapy stratification. Current standard-of-care diagnostics, involving cytomorphological and histological assessment of bone marrow aspirates and trephine biopsies, lack sensitivity, leading to undetected MRD in many patients, and do not allow molecular biomarker assessment.</p><p><strong>Methods: </strong>This study evaluates advanced multi-modal high-sensitivity MRD detection techniques in 509 bone marrow specimens from 108 high-risk neuroblastoma patients across two centers. We employed automatic immunofluorescence plus interphase fluorescence in situ hybridization (AIPF) and reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) panels to quantify disseminated tumor cells (DTCs), disialoganglioside 2 (GD2) and CD56/Neural cell adhesion molecule (NCAM) levels, and adrenergic (ADRN) and mesenchymal (MES)-phenotype mRNA markers.</p><p><strong>Results: </strong>This multi-modal analysis significantly improved MRD detection compared to standard-of-care methods; 395 samples yielded results for RT-qPCR-ADRN, AIPF and CM/histology and 223 showed concordant results (64 positive, 159 negative). 114 samples did not produce results as either no cytospins were prepared (n = 96) or results were inconclusive (all techniques n = 18). AIPF and RT-qPCR complemented each other in detecting MRD and characterizing ADRN- and MES-phenotypes and GD2 immunotherapy target. RT-qPCR-ADRN alone frequently detected low tumor cell burden. High DTC infiltration at diagnosis showed bilateral bone marrow disease, whereas MRD settings often involved only one side. RT-qPCR-MES, despite lower sensitivity, identified 37 additional cases and showed delayed clearance of MES markers post-chemotherapy, with increases prior to relapse.</p><p><strong>Conclusions: </strong>Our findings demonstrate the feasibility of integrating high-sensitivity techniques with standard-of-care assessments in an international multicenter setting. Advanced multi-modal MRD detection, monitoring phenotype switches and assessing immunotherapy targets are crucial for improving patient outcomes in neuroblastoma and other cancers.</p>","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"44 1","pages":"224"},"PeriodicalIF":12.8,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12317575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144769223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endoplasmic reticulum-localized circular RNA FAM13B restrains nasopharyngeal carcinoma lymphatic metastasis through downregulating XBP1.","authors":"Guo-Dong Jia, Si-Yi Xie, Xiao-Yun Li, Liang-Ji Li, Jing Jin, Li-Ting Liu, Xue-Song Sun, Sai-Lan Liu, Qiu-Yan Chen, Lin-Quan Tang, Li Yuan, Hai-Qiang Mai","doi":"10.1186/s13046-025-03468-7","DOIUrl":"10.1186/s13046-025-03468-7","url":null,"abstract":"<p><strong>Background: </strong>Nasopharyngeal carcinoma (NPC) is often diagnosed at an advanced stage due to its hidden location, with 70-80% of patients presenting with cervical lymph node metastasis. This high metastasis rate is a major cause of treatment failure and mortality. Non-coding RNAs, particularly circRNAs, have emerged as key players in tumor development, but their roles in NPC lymph node metastasis and angiogenesis remain unclear. This study aimed to identify key circRNAs involved in NPC lymph node metastasis and elucidate their mechanisms of action.</p><p><strong>Methods: </strong>We identified circFAM13B, a differentially expressed circRNA, using transcriptome sequencing of nasopharyngeal tissues from patients with and without lymph node metastasis. Stable cell lines with circFAM13B overexpression and knockdown were constructed. Functional experiments, including cell invasion, migration, and metastasis assays, were performed in vitro and in vivo. Mechanistic studies involved RNA sequencing, RNA pull-down, and RNA immunoprecipitation assays to explore interacting proteins and signaling pathways.</p><p><strong>Results: </strong>CircFAM13B was downregulated in metastatic tissues and localized in the endoplasmic reticulum (ER). It acted as a tumor suppressor by binding to RBM3 and promoting degradation of uXBP1 mRNA, a key ER stress molecule. This interaction downregulated sXBP1 and CST6, inhibiting lymphangiogenesis and metastasis. Reduced CST6 expression was associated with poor prognosis in NPC.</p><p><strong>Conclusions: </strong>Our study reveals that circFAM13B inhibits ER stress-related pathways in NPC, highlighting its potential as a therapeutic target for lymph node metastasis.</p>","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"44 1","pages":"223"},"PeriodicalIF":12.8,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12312493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144762148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Balancing between cuproplasia and copper-dependent cell death: molecular basis and clinical implications of ATOX1 in cancer.","authors":"Justyna Suwara, Mariusz L Hartman","doi":"10.1186/s13046-025-03486-5","DOIUrl":"10.1186/s13046-025-03486-5","url":null,"abstract":"<p><p>Human antioxidant protein 1 (ATOX1) is an essential regulator of copper homeostasis in cells. By interacting with other proteins involved in controlling the intracellular levels of cuprous ions (Cu⁺), ATOX1 contributes to the import, export, and subcellular distribution of Cu⁺ as it functions within the CTR1-ATOX1-ATP7A/ATP7B axis. For this reason, ATOX1 plays a key role in preventing copper toxicity. Since copper ions have been shown to regulate the activity of a subset of other signaling proteins, ATOX1 can support cell proliferation, migration, and survival. Notably, ATOX1 is the only identified copper chaperone that has transcription factor activity. In this respect, CCND1, MDC1, NCF1, PPA2, and SOD3 have been experimentally validated as transcriptional targets of ATOX1 in distinct types of cells. The multifaceted actions of ATOX1 indicate that its dysregulation can lead to changes in the activity of crucial signaling pathways associated with diverse disorders, including cancer. Indeed, ATOX1 levels are frequently increased in cancer as demonstrated in multiple studies and supported by data available in GEPIA. ATOX1 has been implicated in cancer biology because of its role in the proliferation and metastatic spread of cancer cells and protection from oxidative stress. Additionally, ATOX1 may impact the drug response and resistance of cancer cells by influencing detoxification mechanisms as demonstrated for platinum-based therapies. In turn, the role of ATOX1 in the susceptibility of cancer cells to targeted therapies and immunotherapy remains elusive. This, however, should be a direction of further research considering the recent advances in understanding the complex role of copper in cancer cells, which can be associated with either protumorigenic effects (cuproplasia) or the induction of novel copper-dependent regulated cell death (cuproptosis) to combat cancer cells. Therefore, the disruption of ATOX1-mediated processes could be beneficial for the efficacy of anticancer therapies, although this possibility should be treated with caution because of the dual role of copper in cancer. Moreover, the prognostic value of ATOX1 expression for the clinical outcome of cancer patients needs to be clarified. In this review, we summarize the current state of knowledge about ATOX1 in cancer focusing on its molecular aspects and potential clinical implications.</p>","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"44 1","pages":"222"},"PeriodicalIF":12.8,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12302472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144735029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MRPL21-PARP1 axis promotes cisplatin resistance in head and neck squamous cell carcinoma by inhibiting autophagy through the PI3K/AKT/mTOR signaling pathway.","authors":"Rui Guan, Ce Li, Ruijie Jiao, Jingao Li, Ran Wei, Chen Feng, Shengda Cao, Ye Qian, Jugao Fang, Jun Liu, Wenming Li, Dongmin Wei, Dapeng Lei","doi":"10.1186/s13046-025-03482-9","DOIUrl":"10.1186/s13046-025-03482-9","url":null,"abstract":"<p><strong>Background: </strong>Head and neck squamous cell carcinoma (HNSCC) constitutes a major clinical challenge that severely affects patient survival. Mitochondrial ribosomal protein (MRP) family plays an important role in energy metabolism by participating in mitochondrial oxidative phosphorylation. However, their roles in HNSCC and the underlying mechanisms are still unclear.</p><p><strong>Methods: </strong>Single-cell analysis highlighted MRPL21 as a notable biomarker of HNSCC. Human HNSCC tissues, cell lines, and xenograft models in nude mice were used to explore the expression and function of MRPL21. The mass spectrometry was performed to analyze the potential binding targets of MRPL21. In vitro and in vivo experiments were performed to evaluate the effect of MRPL21 on autophagy and cisplatin resistance. The inhibitory actions of siMRPL21 nanodelivery systems on HNSCC progression were also evaluated in vivo.</p><p><strong>Results: </strong>Clinically, relatively high expression level of MRPL21 was associated with poor prognosis in HNSCC patients, and overexpression of MRPL21 significantly promoted HNSCC tumorigenesis, metastasis, and cisplatin resistance. Mechanistically, MRPL21 upregulated mitochondrial oxidative phosphorylation (OXPHOS) and increased PARylation level, inhibited autophagy through activating the downstream PI3K/AKT/mTOR signaling pathway, and ultimately led to tumor progression and cisplatin resistance in HNSCC.</p><p><strong>Conclusion: </strong>We conclude that MRPL21 is a novel biomarker and therapeutic target of HNSCC progression and cisplatin resistant, which may provide a new approach for overcoming cisplatin resistance in HNSCC patients.</p>","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"44 1","pages":"221"},"PeriodicalIF":12.8,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144719049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparing Xenium 5K and Visium HD data from identical tissue slide at a pathological perspective.","authors":"Mengping Long, Taobo Hu, Weixin Wang, Junshun Gao, Nan Wang, Mats Nilsson","doi":"10.1186/s13046-025-03479-4","DOIUrl":"10.1186/s13046-025-03479-4","url":null,"abstract":"<p><p>Recent advancements in spatial transcriptomics have been largely triggered by two high-resolution technologies: Visium-HD and Xenium in-situ. While sequencing-based Visium HD features a refined bin size of 2 µm and transcriptome wide coverage, Xenium in-situ is a targeted imaging-based detection technology with sub-micron resolution. Herein we use a publicly available lung dataset which contains Visium-HD and Xenium-5K data generated on identical tissue slides to make a bona-fide technical comparison aligned with thorough pathological annotations. Whilst Visium-HD offers a broader gene coverage for detection and likely detects more tumor subclones, Xenium-5K achieves comparable results when robust clustering algorithms are applied. Importantly, from the pathological point of view, the single-cell segmentation accuracy is essential when analyzing irregularly shaped cells, where Xenium may be in favor. At the opposite side, although Xenium-5K based cell segmentation to delineate immune cells, normal lung, and vasculature at cell resolution is decent, it relies on fluorescent signals for transcript detection, which is challenging in heavily pigmented tissues such as melanoma or dust-laden alveolar macrophages, an application scenario for which Visium HD may stand out. From this perspective, pathological derived factors are the prior consideration for selecting an appropriate ST approach under difference research settings including cancer.</p>","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"44 1","pages":"219"},"PeriodicalIF":12.8,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12298044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144719047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}