Biomarker Research最新文献

{"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}

{"title":"Extracellular matrix: unlocking new avenues in cancer treatment.","authors":"Jia Jing Lee, Khuen Yen Ng, Athirah Bakhtiar","doi":"10.1186/s40364-025-00757-3","DOIUrl":"10.1186/s40364-025-00757-3","url":null,"abstract":"<p><p>The extracellular matrix (ECM) plays a critical role in cancer progression by influencing tumor growth, invasion, and metastasis. This review explores the emerging therapeutic strategies that target the ECM as a novel approach in cancer treatment. By disrupting the structural and biochemical interactions within the tumor microenvironment, ECM-targeted therapies aim to inhibit cancer progression and overcome therapeutic resistance. We examine the current state of ECM research, focusing on key components such as collagen, laminin, fibronectin, periostin, and hyaluronic acid, and their roles in tumor biology. Additionally, we discuss the challenges associated with ECM-targeted therapies, including drug delivery, specificity, and potential side effects, while highlighting recent advancements and future directions. This review underscores the potential of ECM-focused strategies to enhance the efficacy of existing treatments and contribute to more effective cancer therapies.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"78"},"PeriodicalIF":9.5,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12117852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144163701","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":"Single cell analysis identified IFN signaling activation contributes to the pathogenesis of pediatric steroid-sensitive nephrotic syndrome.","authors":"Qiu-Yu Li, Fei Liu, Xiaoyi Li, Minchao Kang, Linnan Bai, Tong Tong, Chen Zheng, Yanyan Jin, Xiaojing Zhang, Yi Xie, Dandan Tian, Yuanqing Pan, Jingjing Wang, Haidong Fu, Na Jiao, Junnan Wu, JianHua Mao","doi":"10.1186/s40364-025-00790-2","DOIUrl":"10.1186/s40364-025-00790-2","url":null,"abstract":"<p><strong>Background: </strong>Idiopathic nephrotic syndrome (INS) is a prevalent condition whose recurrence leads to multiple adverse effects. Previous studies on INS pathogenesis primarily focused on immune dysregulation, particularly T-cell changes and their correlation with cytokine shifts. Accumulating evidence suggests that B-cell dysfunction also plays a role. Nevertheless, a comprehensive understanding of the mechanisms and effective treatment strategies remains incomplete.</p><p><strong>Methods: </strong>This study investigates changes in gene expressions and cellular interactions of immune cells at a single-cell level using peripheral blood mononuclear cells (PBMCs). And subsequently validated through quantitative PCR (qPCR), enzyme-linked immunosorbent assay (ELISA), and flow cytometry.</p><p><strong>Results: </strong>We identified seven main clusters using unsupervised clustering of 103,213 high-quality single cells. Through unsupervised clustering, patient-specific T cells (IFI44L + CD4 + T cells) that exhibited a pronounced elevation of interferon-stimulated genes (ISGs) is identified. Activation of ISGs and interferon (IFN)-related pathways are also observed in other clusters. Specifically, this study demonstrates that interferon-γ (IFN-γ) plays a crucial role by promoting the interaction between B-cell activating factor (BAFF) and receptors on B cells. This interaction triggers the release of autoantibodies, thereby initiating INS pathogenesis. Furthermore, telitacicept has shown efficacy in treating pediatric patients with frequent relapse NS(FRNS).</p><p><strong>Conclusions: </strong>Overall, our findings underscore the role of interferon and its related pathways in INS pathogenesis, providing novel therapeutic interventions for NS.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"77"},"PeriodicalIF":9.5,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144288","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":"Early kinetics of serum amyloid A predict clinical benefit to first-line chemoimmunotherapy and immunotherapy in advanced non-small cell lung cancer: a retrospective analysis.","authors":"Wei Du, Jianhua Zhan, Kai Wu, Yanming Wang, Li Zhang, Shaodong Hong","doi":"10.1186/s40364-025-00791-1","DOIUrl":"10.1186/s40364-025-00791-1","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for advanced non-small cell lung cancer (NSCLC), yet durable responses remain limited in a subset of patients. Serum amyloid A (SAA), an acute-phase protein linked to systemic inflammation, may reflect dynamic immune responses. This retrospective study analyzed 242 advanced NSCLC patients treated with first-line chemoimmunotherapy or immunotherapy between August 2016 and December 2024. Patients were stratified by early SAA kinetics into flare-responders (initial rise followed by decline), responders (sustained decline), and non-responders. Clinical outcomes, including progression-free survival (PFS) and overall survival (OS), were evaluated using Kaplan-Meier and Cox regression analyses. In the chemoimmunotherapy cohort, SAA flare-responders demonstrated significantly prolonged median PFS (29.8 months, 95% CI: 9.95-49.65; HR: 0.31, 95% CI: 0.15-0.64; p < 0.01) compared to non-responders (7.4 months, 95% CI: 4.67-10.13). Similarly, in the immunotherapy cohort, SAA flare-responders showed superior PFS. (19.9 vs. 2.1 months, HR 0.31, p < 0.01). Multivariate analysis confirmed early SAA kinetics as an independent prognostic factor for both PFS and OS in both treatment groups. Early SAA kinetics serve as a promising non-invasive biomarker for predicting clinical outcomes in advanced NSCLC treated with first-line chemoimmunotherapy or immunotherapy. These findings highlight SAA kinetics as a potential non-invasive biomarker and monitoring SAA dynamics may aid in identifying patients with higher likelihood of clinical benefit; however, prospective studies are required to determine its utility in guiding therapeutic decisions.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"76"},"PeriodicalIF":9.5,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132047","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":"The progress and prospects of targeting the adenosine pathway in cancer immunotherapy.","authors":"Yuying Yang, Lin Zhu, Yantao Xu, Long Liang, Li Liu, Xiang Chen, Hui Li, Hong Liu","doi":"10.1186/s40364-025-00784-0","DOIUrl":"10.1186/s40364-025-00784-0","url":null,"abstract":"<p><p>Despite the notable success of cancer immunotherapy, its effectiveness is often limited in a significant proportion of patients, highlighting the need to explore alternative tumor immune evasion mechanisms. Adenosine, a key metabolite accumulating in hypoxic tumor regions, has emerged as a promising target in oncology. Inhibiting the adenosinergic pathway not only inhibits tumor progression but also holds potential to enhance immunotherapy outcomes. Multiple therapeutic strategies targeting this pathway are being explored, ranging from preclinical studies to clinical trials. This review examines the complex interactions between adenosine, its receptors, and the tumor microenvironment, proposing strategies to target the adenosinergic axis to boost anti-tumor immunity. It also evaluates early clinical data on pharmacological inhibitors of the adenosinergic pathway and discusses future directions for improving clinical responses.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"75"},"PeriodicalIF":9.5,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12090549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103166","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}