Biomarker Research最新文献

{"title":"Adipose-derived stem cell exosomes: mechanisms and therapeutic potentials in wound healing.","authors":"Heting Feng, Song Gong, Jiafeng Liu, Sis Aghayants, Yiling Liu, Min Wu, Yiping Wu, Jingyu Song","doi":"10.1186/s40364-025-00801-2","DOIUrl":"10.1186/s40364-025-00801-2","url":null,"abstract":"<p><p>Wound healing is a complex, multi-stage process that restores skin integrity through coordinated cellular and molecular interactions. Among the emerging therapeutic strategies, adipose-derived stem cell exosomes (ADSC-Exos) attract significant attention due to their potent regenerative capabilities. ADSC-Exos contribute to wound repair by modulating inflammatory responses, promoting cellular proliferation and migration, stimulating angiogenesis, and facilitating collagen remodeling. These exosomes carry a diverse array of bioactive molecules including cytokines, non-coding RNAs (ncRNAs), and proteins, that are delivered to target cells, thereby orchestrating the intricate processes involved in tissue regeneration. Recent advancements in exosome engineering, such as genetic modification, pharmacological preconditioning, hypoxic treatment, and incorporation with biomaterials, markedly improve the therapeutic efficacy of ADSC-Exos. This review summarizes the underlying mechanisms and therapeutic potential of ADSC-Exos in wound healing, offering new perspectives for developing exosome-based regenerative therapies. Nevertheless, challenges persist regarding the large-scale production, standardized isolation, and clinical translation of ADSC-Exos. Future research should aim to enhance exosome yield and purity, elucidate the mechanisms governing exosome biogenesis, and validate their clinical efficacy through well-designed trials.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"88"},"PeriodicalIF":9.5,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337242","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":"Multi-omics: a bridge connecting genotype and phenotype for epilepsy?","authors":"Nan-Nan Wang, Fei Cao, Lin-Han Zhang, Yi-Fei Zheng, Da Xu","doi":"10.1186/s40364-025-00798-8","DOIUrl":"10.1186/s40364-025-00798-8","url":null,"abstract":"<p><p>Epilepsy is a collection of neurological disorders characterized by abnormal neuronal discharges, resulting in spontaneous and recurrent unprovoked seizures. Despite the use of over 20 anti-seizure drugs, conventional one-size-fits-all approaches are insufficient to meet the needs of all patients, and about 1/3 patients developed drug-resistant epilepsy. Recently, the establishment of precision medicine-based clinical management for epilepsy may bring new insights, especially omics-based approaches. Single omics approach is limited to addressing questions from a single molecular perspective. Whereas multi-omics approaches enable a comprehensive characterization of multiple molecules, revealing the complex molecular dysregulation networks underlying different epilepsy phenotypes. Furthermore, multi-omics methods have catalyzed a paradigm shift in scientific inquiry, transitioning from traditional hypothesis-driven types to data-driven research architectures. Despite the full potential of multi-omics research yet to be realized, its application in epilepsy holds great promise, from the discovery of epileptic biomarkers to personalized management. In this review, we performed a comprehensive overview of the omics technologies and multi-omics integration strategies, followed by an exploration of their role in enhancing the management of epilepsy treatment and care, hoping to provide new directions for future researches.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"86"},"PeriodicalIF":9.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12175374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327743","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":"A novel therapeutic strategy for osteosarcoma using anti-GD2 ADC and EZH2 inhibitor.","authors":"Jing Shan, Zicheng Lin, Harunor Rashid, Peng Huang, Lei Qiang, Yihao Liu, Guanlu Shen, Yuchen Li, Jiaming Cui, Zhi Su, Hanbo Wang, Bixuan Cao, Cheng Zhou, Veysel Kayser, Bo Ning","doi":"10.1186/s40364-025-00800-3","DOIUrl":"10.1186/s40364-025-00800-3","url":null,"abstract":"<p><p>Osteosarcoma is the commonest malignant bone tumour in children, with a poor prognosis due to limited treatment options. Antibody-drug conjugates (ADCs) offer targeted therapeutic potential but are limited by the low expression of specific antigens like disialoganglioside (GD2) on osteosarcoma cells. This study aimed to enhance the efficacy of an anti-GD2 ADC by combining it with the enhancer of zeste homolog 2 (EZH2) inhibitor tazemetostat to upregulate GD2 expression and improve treatment outcomes. We constructed an ADC by conjugating naxitamab to mertansine (DM1) via an SMCC linker. Human osteosarcoma cell lines (U2OS and 143B) were treated with tazemetostat to increase GD2 expression. In vitro experiments included apoptosis assays, gene expression analysis, and flow cytometry. We evaluated in vivo efficacy in mouse xenograft models by measuring tumour growth and pulmonary metastases. Tazemetostat treatment significantly increased GD2 expression in U2OS and 143B cell lines. The anti-GD2 ADC induced apoptosis via the mitochondrial pathway, as shown by increased expression of apoptosis-related genes and higher apoptosis rates. In vivo, the ADC significantly inhibited tumour growth and reduced pulmonary metastasis. These therapeutic effects were further enhanced when the ADC was combined with tazemetostat. Combining anti-GD2 ADC therapy with EZH2 inhibition effectively improves targeted treatment for osteosarcoma. Tazemetostat upregulates GD2 expression, enhancing the ADC's efficacy. This dual-approach strategy demonstrates the potential of integrating epigenetic modulation with targeted drug delivery, offering a promising path for improving outcomes in hard-to-treat cancers.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"87"},"PeriodicalIF":9.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12177979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327742","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":"Microbiome multi-omics analysis reveals novel biomarkers and mechanisms linked with CD etiopathology.","authors":"Gerard Serrano-Gómez, Francisca Yañez, Zaida Soler, Marc Pons-Tarin, Luis Mayorga, Claudia Herrera-deGuise, Natalia Borruel, Antonio Rodriguez-Sinovas, Marta Consegal, Isaac Manjón, Sara Vega-Abellaneda, Chaysavanh Manichanh","doi":"10.1186/s40364-025-00802-1","DOIUrl":"10.1186/s40364-025-00802-1","url":null,"abstract":"<p><strong>Background: </strong>The gut microbiome plays a key role in the development of inflammatory bowel disease (IBD), as imbalances in microbial composition are associated with immune dysfunction. However, the specific mechanisms by which certain microorganisms contribute to this process remain unclear.</p><p><strong>Methods: </strong>Here, we employed a multi-omics approach on fecal samples to identify novel microbiome markers and elucidate mechanisms underlying IBD. Shotgun metagenomics was applied to 212 samples (850 in total with validation cohort), shotgun metatranscriptomics to 103 samples and metabolomics to 105 samples. Machine learning techniques were used to predict disease and the three omics data were integrated to propose a mechanistic role of the microbiota.</p><p><strong>Results: </strong>Metagenomic analysis identified Crohn's disease (CD)-specific microbiome signatures, including a panel of 20 species that achieved a high diagnostic performance, with an area under the ROC curve (AUC) of 0.94 in an external validation set. Metatranscriptomic analysis revealed significant alterations in microbial fermentation pathways in CD, but not in ulcerative colitis (UC), highlighting disruptions that explain the depletion of butyrate-a key anti-inflammatory metabolite-observed in metabolomics analysis. Integrative multi-omics analyses further identified active virulence factor genes in CD, predominantly originating from the adherent-invasive Escherichia coli (AIEC). Notably, these findings unveiled novel mechanisms, including E. coli-mediated aspartate depletion and the utilization of propionate, which drives the expression of the ompA virulence gene, critical for bacterial adherence and invasion of the host's macrophages. Interestingly, these microbiome alterations were absent in UC, underscoring distinct mechanisms of disease development between the two IBD subtypes.</p><p><strong>Conclusions: </strong>In conclusion, our study not only identifies promising novel biomarkers with strong diagnostic potential, which could be valuable in challenging clinical scenarios, but also offers an integrated multi-omics perspective on the microbial mechanisms underlying inflammation and virulence in Crohn's disease.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"85"},"PeriodicalIF":9.5,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12172205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310818","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":"Targeted inhibition of Ninjurin2 promotes chemosensitivity in chemoresistant gastric cancer by suppressing cancer-initiating cells.","authors":"Hyo Shik Shin, Jae-Il Choi, Hye Won Chung, Hee Jung Park, Hak Park, John Hoon Rim, Jong-Baeck Lim","doi":"10.1186/s40364-025-00792-0","DOIUrl":"10.1186/s40364-025-00792-0","url":null,"abstract":"<p><strong>Background: </strong>The combination of epirubicin, cisplatin, and 5-fluorouracil (ECF) is widely used for gastric cancer treatment. However, cancer cells can acquire chemoresistance over multiple treatment cycles, leading to recurrence. This study aimed to investigate a novel biomarker for predicting ECF resistance and its biological roles in gastric cancer.</p><p><strong>Methods: </strong>ECF-resistant (ECF-R) gastric cancer cell lines were established through stepwise ECF treatment. Transcriptome analysis was performed to identify resistance-related genes, which were validated in tumor organoids and in vivo models. Additionally, gastric cancer patient tumor tissues were analyzed for clinical relevance.</p><p><strong>Results: </strong>Transcriptome analysis revealed that NINJURIN2 and CD44 were highly expressed in ECF-R cells but rarely expressed in normal gastric tissues. NINJURIN2 inhibition significantly increased chemosensitivity to ECF in vitro and in vivo. Liquid chromatography-tandem mass spectrometry identified periostin as a binding partner of NINJURIN2, mediating chemoresistance. Furthermore, VAV2 phosphorylation was markedly upregulated in ECF-R cells but was inhibited by NINJURIN2 knockdown. Clinical analysis showed that high NINJURIN2 expression correlated with poor survival outcomes in gastric cancer patients.</p><p><strong>Conclusion: </strong>Our findings suggest that NINJURIN2 can be used as a novel biomarker for chemoresistant gastric cancer patients and that inhibiting NINJURIN2 along with standard chemotherapy could prevent chemoresistance-associated relapse in gastric cancer.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"84"},"PeriodicalIF":9.5,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12168268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303575","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":"Tumor-specific MHC-II guides anthracycline exemption and immunotherapy benefit in breast cancer.","authors":"Zehao Wang, Yanhui Wang, Zhishuang Gao, Yue Zhou, Xiaoting Chen, Rui Xu, Yangsiyuan Zhao, Yi Zhang, Bingqiu Xiu, Jing Liu, Zhiming Shao, Shengmei Gu, Jingyan Xue, Jiong Wu","doi":"10.1186/s40364-025-00797-9","DOIUrl":"10.1186/s40364-025-00797-9","url":null,"abstract":"<p><strong>Background: </strong>Anthracycline-based chemotherapy, while foundational in breast cancer treatment, confers substantial cardiotoxicity. Identifying biomarkers to guide anthracycline exemption without compromising efficacy has remained an unresolved clinical challenge for decades.</p><p><strong>Methods: </strong>We conducted multi-cohort spatial-omics and clinical validation integrating 345 early-stage triple-negative breast cancer (eTNBC) and 167 HER2 + breast cancer patients from Fudan University Shanghai Cancer Center (FUSCC) cohorts, alongside 150 eTNBC patients from a validation cohort. Tumor-specific MHC-II (tsMHC-II) expression was quantified via multiplex immunohistochemistry (mIHC). Mechanistic insights were derived from the NeoTRIP immunotherapy spatial cohort, I-SPY2 trial data, TCGA database, ATAC-seq chromatin profiling, ChIP, and patient-derived organoid (PDO)-immune cell co-culture systems.</p><p><strong>Results: </strong>In eTNBC, high tsMHC-II expression predicted improved disease-free survival (DFS) and comparable overall survival (OS) with paclitaxel-carboplatin (PCb) versus anthracycline-sequential paclitaxel (EC-P), identifying tsMHC-II as a predictive marker for anthracycline exemption. High tsMHC-II correlated with prolonged DFS and OS in both TNBC and HER2 + subtypes. Multi-omics including spatial and transcriptional cohorts revealed tsMHC-II-high tumors harbor immune-rich microenvironments with elevated cytotoxic T cells, B cells, and antigen-presenting cells. Validation in NeoTRIP and I-SPY2 cohorts demonstrated superior immunotherapy response in tsMHC-II-high patients. Mechanistically, ATAC-seq, ChIP and PDO co-culture models confirmed that KAT2B upregulated tsMHC-II via CIITA promoter acetylation, sustaining immunotherapeutic vulnerability.</p><p><strong>Conclusion: </strong>TsMHC-II serves as a dual biomarker for adjuvant anthracycline chemotherapy exemption and neoadjuvant immunotherapy stratification in TNBC, driven by KAT2B-mediated epigenetic remodeling. These findings advance precision strategies to reduce anthracycline toxicity while enhancing immune activation in eTNBC.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"83"},"PeriodicalIF":9.5,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12150567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144267898","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":"RNA epigenetic modifications as dynamic biomarkers in cancer: from mechanisms to clinical translation.","authors":"Yingchao Zhao, Xiang Chen, Xingli Zhang, Hong Liu","doi":"10.1186/s40364-025-00794-y","DOIUrl":"10.1186/s40364-025-00794-y","url":null,"abstract":"<p><p>RNA modifications are crucial for post-transcriptional gene regulation. Research on RNA modifications has become a novel frontier of epitranscriptomics. Up to now, over 170 kinds of modifications have been identified on mRNA and diverse non-coding RNA. Three classes of proteins (writers, erasers, and readers) regulate the addition, removal, and identification of epigenetic marks, thus affecting RNA biological functions. Increasing evidence identifies the dysregulation of RNA modifications in different cancer types and the therapeutic potential of targeting RNA-modifying enzymes. The ability of RNA modifications to improve mRNA stability and translation efficacy and decrease immunogenicity has been exploited for the clinical use of mRNA cancer vaccines. This review aims to shed light on several vital cap, tail, and internal modifications of RNA with a focus on the connection between RNA epigenetic pathways and cancer pathogenesis. We further explore the clinical potential of RNA modifications as dynamic biomarkers for cancer diagnosis, prognosis, and therapeutic response prediction, addressing both technological challenges and translational opportunities. Finally, we analyze the limitations of current studies and discuss the research focus in the future.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"81"},"PeriodicalIF":9.5,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12145623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250858","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":"Heterogeneous characteristics of γδ T cells in peripheral blood of diffuse large B-cell lymphoma.","authors":"Peng-Lin Wang, Wen-Pu Lai, Jia-Mian Zheng, Xiao-Fang Wu, Jian-Nan Zhan, Ting-Zhuang Yi, Zhen-Yi Jin, Xiu-Li Wu","doi":"10.1186/s40364-025-00795-x","DOIUrl":"10.1186/s40364-025-00795-x","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Diffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous disease with variable clinical and molecular features. Studies have highlighted the significant role of γδ T cells in the survival of leukemia patients. However, the heterogeneity of γδ T cells and their impact on clinical correlation in the peripheral blood of patients with DLBCL remain unclear.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Method: &lt;/strong&gt;Single-cell RNA sequencing (scRNA-seq) was employed on 9 blood samples, sourced from 6 patients with diffuse large B-cell lymphoma (DLBCL) and 3 healthy individuals (HIs), to delineate clinically pertinent γδ T cell states and subsets in DLBCL patients. Flow cytometry was then employed to validate the relationship between DLBCL prognosis and γδ T cell subsets.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Result: &lt;/strong&gt;Our study integrated genetic drivers through consensus clustering, leading to the identification of 6 distinct γδ T cell subsets in DLBCL and HIs. These subsets include a naïve γδ T cell subset characterized by TCF7 and LEF1 expression, a memory γδ T cell subset sharing common genes such as GZMK, IL7R, an anti-tumor γδ T cell subset with overexpression of IFNG, TNF, and CD69, and two subsets exhibiting TIGIT overexpression indicative of an exhausted γδ T cell phenotype. Additionally, a cytotoxic γδ T cell subset marked by increased NKG7 and GZMB levels was identified. Our results revealed that while γδ T cells possess anti-tumor capacities, their functional effectiveness is diminished due to differentiation into exhausted subpopulations. Several clusters with high cytotoxicity scores also showed elevated exhaustion scores (C13-γδ-TIGIT.1, C14-γδ-TIGIT.2), suggesting the presence of a population in DLBCL samples that is simultaneously exhausted and cytotoxic. In particular, the TIGIT.2 γδ T cell subset manifests a more pronounced exhaustion score relative to TIGIT.1 γδ T cell subset, indicating differential levels of cellular exhaustion among these groups. Our analysis reveals a significant correlation between high expression of TIGIT γδ T cell subsets and poorer patient prognoses. We also discovered unique expression profiles within these subgroups: TIGIT.1 γδ T cells are marked by elevated CXCR4 expression, contrasting with the TIGIT.2 γδ T cell subgroup which exhibits increased CX3CR1 expression. Pseudotime analysis implies a potential differentiation trajectory from naïve and GZMK γδ T cells to various terminally differentiated subsets, with genes associated with stemness (e.g., TCF-1) subsequently downregulated. These findings suggest that TIGIT.2 subset may be further along in the differentiation trajectory, potentially representing a more terminally differentiated state than TIGIT.1 subset. According to our clinical validation cohort, the TIGIT&lt;sup&gt;+&lt;/sup&gt; γδ T cell subset is highly expressed in patients and correlates with poor prognosis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;We identified genetic subtypes of γδ T cells with distinct genot","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"82"},"PeriodicalIF":9.5,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12145656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250857","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":"Epigenetic regulation of histone modifications in glioblastoma: recent advances and therapeutic insights.","authors":"Li Zhang, Yang Yang, Yanchu Li, Chenyu Wang, Chenbin Bian, Hongbin Wang, Feng Wang","doi":"10.1186/s40364-025-00788-w","DOIUrl":"10.1186/s40364-025-00788-w","url":null,"abstract":"<p><p>Glioblastoma (GBM) is the most common primary malignant brain tumor, characterized by its aggressive behavior, limited treatment options, and poor prognosis. Despite advances in surgery, radiotherapy, and chemotherapy, the median survival of GBM patients remains disappointingly short. Recent studies have underscored the critical role of histone modifications in GBM malignant progression and therapy resistance. Histones, protein components of chromatin, undergo various modifications, including acetylation and methylation. These modifications significantly affect gene expression, thereby promoting tumorigenesis and resistance to therapy. Targeting histone modifications has emerged as a promising therapeutic approach. Numerous pre-clinical studies have evaluated histone modification agents in GBM, including histone deacetylase inhibitors and histone methyltransferase inhibitors. These studies demonstrate that modulating histone modifications can alter gene expression patterns, inhibit tumor growth, induce apoptosis, and sensitize tumor cells to conventional treatments. Some agents have advanced to clinical trials, aiming to translate preclinical efficacy into clinical benefit. However, clinical outcomes remain suboptimal, as many agents fail to significantly improve GBM patient prognosis. These challenges are attributed to the complexity of histone modification networks and the adaptive responses of the tumor microenvironment. This review provides a comprehensive overview of epigenetic regulation mechanisms involving histone modifications in GBM, covering their roles in tumor development, tumor microenvironment remodeling, and therapeutic resistance. Additionally, the review discusses current clinical trials targeting histone modifications in GBM, highlighting successes, limitations, and future perspectives.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"80"},"PeriodicalIF":9.5,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12125905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192526","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":"Transcriptomic analysis of transformed small-cell lung cancer from EGFR-mutated lung adenocarcinoma reveals distinct subgroups and precision therapy opportunities.","authors":"Hao Sun, Chan-Yuan Zhang, Xiu-Hao Zhang, Zai-Xian Tai, Jun-Wei Su, Xiao-Cheng Lin, Shi-Ling Zhang, Yu-Fa Li, Chao Zhang, Miao Cai, Xu-Chao Zhang, Hua-Jun Chen, Qing Zhou, Yi-Long Wu, Wei-Neng Feng, Jin-Ji Yang","doi":"10.1186/s40364-025-00789-9","DOIUrl":"10.1186/s40364-025-00789-9","url":null,"abstract":"<p><strong>Background: </strong>Small-cell lung cancer (SCLC) transformation is one of the major mechanisms of resistance to Epidermal Growth Factor Receptor tyrosine kinase inhibitors (EGFR-TKIs). Chemotherapy is typically the recommended treatment for transformed SCLC (T-SCLC), similar to primary SCLC. However, the benefits of chemotherapy alone are minimal. Prior research highlights differences between the biological traits of T-SCLC and primary SCLC or EGFR-mutated lung adenocarcinoma (LUAD). This study aims to elucidate the molecular characteristics of T-SCLC and identify potential treatment modalities.</p><p><strong>Methods: </strong>We retrospectively collected tissue samples from LUAD, T-SCLC post-EGFR-TKI resistance, and primary SCLC. Genomics, transcriptomics, and proteomics were performed to clarify the differences between T-SCLC, LUAD, and primary SCLC. Hierarchical clustering analysis was then used to categorize the molecular subtype of T-SCLC, followed by a survival analysis based on these subtypes.</p><p><strong>Results: </strong>A study involving 61 patients investigated differences between LUAD, SCLC, and primary SCLC. RNA sequencing revealed distinct gene expression variations, particularly up-regulation in PPM1E, INSM1, and KCNC1 genes in T-SCLC. Pathway analysis linked T-SCLC to the cell cycle and neural differentiation. By conducting Hierarchical clustering analysis on RNA-seq data, the entire population can be categorized into two distinct groups. While certain T-SCLC showed similarities and differences compared to SCLC, with subtypes: LUAD-like and Non-LUAD-like. Notably, the LUAD-like subtype had significantly higher NKX2-1 expression (mean 371.8 vs. 41.8, P < 0.0001). T-SCLC treatment approaches were categorized into matched and unmatched groups, delineated by the alignment of specific therapies with corresponding pathologies. The matched group (13 cases) exhibited a significantly prolonged median progression-free survival compared to the unmatched group (10 cases) (5.4 months vs. 3.6 months, P = 0.02).</p><p><strong>Conclusions: </strong>T-SCLC exhibits marked molecular distinctiveness, setting it apart not only from LUAD but also from classical SCLC. This distinction extends to its classification into two discernible molecular subtypes: LUAD-like and Non-LUAD-like. Customizing therapeutic protocols to align with these specific subtypes have the potential to identify the most appropriate treatment for T-SCLC.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"79"},"PeriodicalIF":9.5,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12121208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144175553","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}