Cancer letters最新文献

{"title":"YY1-glycolytic axis promotes high glucose-induced cancer stemness in endometrial cancer: A multi-omics guided therapeutic strategy","authors":"Xiao Yang ,&nbsp;Chengcheng Li ,&nbsp;Yuan Cheng ,&nbsp;Shaojie Qin ,&nbsp;Lingpu Zhang ,&nbsp;Ling Zhou ,&nbsp;Jingyi Zhou ,&nbsp;Haihua Xiao ,&nbsp;Yu Bai ,&nbsp;Jianliu Wang","doi":"10.1016/j.canlet.2025.217936","DOIUrl":"10.1016/j.canlet.2025.217936","url":null,"abstract":"<div><div>Abnormal glucose metabolism in patients with diabetes mellitus or hyperglycaemia is a key factor leading to poor prognosis of endometrial cancer (EC) and warrants further exploration of its underlying mechanisms. In this study, we employed an integrative multiomics approach, including proteomics, transcriptomics, nontargeted metabolomics and single-cell metabolomics, and revealed that high glucose promotes EC cell stemness, thereby promoting tumour progression and reducing the sensitivity of EC cells to cisplatin (platinum-Pt^II). Mechanistically, there is a significant association between enhanced stemness and increased glycolytic activity in EC cells, and the transcription factor YY1 was found to be a key regulator of PDK1, CD133, and CD44 under high-glucose conditions, with YY1 binding to their promoter regions. Inhibiting YY1 expression effectively attenuates the stem cell properties of tumour cells and increases their sensitivity to cisplatin. Furthermore, we developed ROS-responsive nanoparticles for the codelivery of C8-Pt^IV-COOH and YY1 siRNA (NP-Pt^IV/siYY1), which synergistically amplify antitumour effects and chemosensitivity in patient-derived xenograft (PDX)-bearing mice with diabetes. Taken together, our results demonstrated that YY1 is a promising therapeutic target for inhibiting EC stemness and overcoming chemoresistance, particularly under high-glucose conditions.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"632 ","pages":"Article 217936"},"PeriodicalIF":10.1,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advanced ensemble staking model employing cfDNA fragmentation for early detection of esophageal and gastric cancer","authors":"Shitong Cheng ,&nbsp;Yusong Luo ,&nbsp;Xiaolong Dong ,&nbsp;Meng-yuan Liu ,&nbsp;Zhaoqi Wu ,&nbsp;Lu Xu ,&nbsp;Honghao Yin ,&nbsp;Xin Li ,&nbsp;Sha Shi ,&nbsp;Huan Zhai ,&nbsp;Jia Li ,&nbsp;Chuan He ,&nbsp;Ying Xiong ,&nbsp;Linan Bao ,&nbsp;Siyu Li ,&nbsp;Siyu Zhang ,&nbsp;Xiao Sun ,&nbsp;Qingxin Xie ,&nbsp;Ningyou Li ,&nbsp;Hua Bao ,&nbsp;Hong Shang","doi":"10.1016/j.canlet.2025.217945","DOIUrl":"10.1016/j.canlet.2025.217945","url":null,"abstract":"<div><div>Esophageal and gastric cancers are aggressive malignancies with poor prognoses due to late-stage diagnosis. Our study recruited 275 healthy participants, 201 gastric cancer patients, 74 esophageal patients and 103 patients with precancerous conditions. The participants were assigned into training and validation cohorts. After processing a low-depth whole genome sequencing for all plasma samples, a stacked ensembled model was constructed, integrating three cfDNA fragmentomic features: Copy Number Variation, Fragment Size Profile, and Fragment Based Methylation. The multi-dimensional model was trained with 5-fold cross-validation, and its performance was evaluated through validation. The detection sensitivity and specificity were validated at 95 % specificity of training set. The stacked ensemble model achieved an AUC of 0.967 in the validation dataset. At a 95 % specificity threshold, the model attained a high sensitivity of 79.2 %, underscoring its clinical utility in distinguishing cancer from healthy individuals. Notably, it achieved sensitivity of 77.4 % and 68.3 % for stage I cases in training and validation cohorts, respectively. The model also identified precancerous conditions effectively, with an AUC of 0.828 and sensitivity of 53.8 % and 71.4 % for gastric and esophageal precancer lesions, while maintaining clear score distinctions in specifying benign diseases. Overall, our stacked model achieved high sensitivity in identifying esophageal and gastric cancer, offering a strong, non-invasive alternative to endoscopy. This approach supports timely intervention and improved patient outcomes by enabling earlier and more targeted treatment.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"631 ","pages":"Article 217945"},"PeriodicalIF":9.1,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144696859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual regulation of FZD1/7 by IGF2BP3 enhances stem-like properties and carboplatin resistance in triple-negative breast cancer.","authors":"Meng-Yuan Cai, Peng Yin, Zi-Wen Wang, Yu-Zhou Huang, Yu-Xin Wang, Kei-Fei Wu, Xu Zhang, Liang Shi, Ji-Fu Wei, Qiang Ding","doi":"10.1016/j.canlet.2025.217944","DOIUrl":"10.1016/j.canlet.2025.217944","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) progression is driven by cancer stem cells (CSCs), contributing to chemoresistance and tumor recurrence. N6-methyladenosine (m6A) modification plays a critical role in regulating CSC plasticity; however, the key m6A regulators in TNBC-CSCs remain poorly defined. Here, we identified IGF2BP3 as a dominant m6A reader enriched in TNBC-CSCs through transcriptomic analysis of the TCGA-BRCA dataset and validation by fluorescence-activated cell sorting (FACS). Functional assays demonstrated that IGF2BP3 knockdown markedly impaired stem-like properties and sensitized CSCs to carboplatin. Mechanistically, IGF2BP3 directly bound to the 3'-untranslated regions of frizzled class receptor 1 and 7 (FZD1/7) mRNAs in an m6A-dependent manner, stabilizing their transcripts and promoting heterodimerization. This interaction activated the β-catenin pathway by facilitating nuclear translocation of non-phosphorylated β-catenin (Ser37/Thr41). RBM15 contributed to the m6A methylation of FZD1/7, enhancing IGF2BP3 recognition. Notably, Fz7-21, a small-molecule inhibitor of FZD1/7, phenocopied the effects of IGF2BP3 knockdown, disrupting CSC maintenance and homologous recombination repair (HRR). Moreover, Fz7-21 synergized with carboplatin to enhance its therapeutic efficacy in TNBC-CSCs. These findings establish IGF2BP3 as a central m6A reader that promotes stemness and carboplatin resistance via FZD1/7 stabilization and β-catenin signaling activation. Targeting IGF2BP3 and FZD1/7 have therapeutic potential to eliminate cancer stem cells and reduce carboplatin dosage in TNBC treatment.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"217944"},"PeriodicalIF":10.1,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-fat diet driven post-operative colon cancer recurrence is dependent upon genetic susceptibility to deoxycholic acid","authors":"Ryan Morgan ,&nbsp;Mohammad Amin Bayat Tork ,&nbsp;Zitong Lin ,&nbsp;Claire Wild ,&nbsp;Luke R. Frietze ,&nbsp;Sihao Huang ,&nbsp;Meejeon Roh ,&nbsp;Andrea Olivas ,&nbsp;Colin W. Steele ,&nbsp;Tao Pan ,&nbsp;Benjamin D. Shogan","doi":"10.1016/j.canlet.2025.217943","DOIUrl":"10.1016/j.canlet.2025.217943","url":null,"abstract":"<div><div>The development of postoperative recurrent tumors or metastasis following surgical resection of colorectal cancer remains a major obstacle to colon cancer cure. While a high-fat diet is a risk factor for the development of recurrence, studies that examine the molecular mechanism by which diet drives postoperative tumors have been lacking. Here, using a murine model that mimics postoperative tumor formation, we show that the tumorigenic influence of a high-fat diet strongly depends on the genetic backbone of the primary tumor cells. We identify deoxycholic acid as a major contributor to the promotion of tumor recurrence only when the primary cancer cell has an APC-driving mutation. We investigate the deoxycholic acid effect on the proliferation of organoids and identify the organoid response to deoxycholic acid treatment, including the transcriptome expression and transfer RNA abundance, modification, and charging. The integrated analysis of mRNA and tRNA sequencing results reveals enhanced decoding of codons in proliferation-promoting genes. Our results provide a new understanding of how both diet and tumor genetics together lead to postoperative colorectal cancer recurrence.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"631 ","pages":"Article 217943"},"PeriodicalIF":9.1,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144696858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating cytokine profiling and clustering identify biomarker predicting efficacy of ICI in combination with chemotherapy","authors":"Xiaotian Xu ,&nbsp;Yiling Li ,&nbsp;Shiran Sun ,&nbsp;Xianlong Lin ,&nbsp;Wenfeng Zhang ,&nbsp;Yue Wu ,&nbsp;Baojun Wei ,&nbsp;Danfei Xu ,&nbsp;Cuiling Zheng ,&nbsp;Hezhi Fang ,&nbsp;Wei Cui","doi":"10.1016/j.canlet.2025.217918","DOIUrl":"10.1016/j.canlet.2025.217918","url":null,"abstract":"<div><div>The combination of chemotherapy can enhance the efficacy of immune checkpoint inhibitors (ICIs), but requires precise patient stratification and biomarker screening. Cytokines influence immunotherapy outcomes, and multiplex cytokine profiling aids in identifying predictive biomarkers for ICIs. We analyzed 1331 plasma samples (1025 untreated pan-cancer patients and 306 healthy controls), including 238 receiving ICIs plus chemotherapy. Cytokine clusters were identified via non-negative matrix factorization. Cluster effected on early response and progression-free survival (PFS) were evaluated, and a Cytokine-based ICI Survival Index (CISI) was developed. The effect of specific cytokines on anti-programmed death 1 (PD1) treatment was verified in vivo. Thus, three inflammatory clusters were identified: Cluster 1 (high IFN-γ/IL-8/IL-1β, proinflammatory), Cluster 2 (high IL-6), and Cluster 3 (high IL-5/IL-17, Th2 activation). Cluster 3 showed superior PFS (HR = 2.44/3.84, p = 0.00011) and response rates (85.42 % vs. 54.33 %/61.90 %, p = 0.00075) versus Clusters 1&amp;2. High IFN-γ/IL-8 predicted poorer outcomes. The CISI model, incorporating cytokine clusters and clinical variables (treatment, IL-10, monocyte-to-lymphocyte ratio, and M stage), outperformed conventional biomarkers programmed death-ligand 1 (PD-L1) and IL-8 in predictive efficiency [Concordance indexes (C-indexes) = 0.75 vs. 0.55 and 0.56]. In vivo studies confirmed the effects on anti-PD1 efficacy by characteristic cytokines in clusters. In conclusion, our cytokine clustering based on multi-cytokine profiles and CISI model predicted prognosis and immunotherapeutic response in tumor patients, providing new insights into personalized cancer therapy strategies.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"631 ","pages":"Article 217918"},"PeriodicalIF":9.1,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144679108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of KAT6A enhances immunotherapy efficacy in colorectal cancer by activating interferon response","authors":"Shuling Han ,&nbsp;Zhuo Chen ,&nbsp;Chang Hong ,&nbsp;Tianjiao Dang ,&nbsp;Futing Bai ,&nbsp;Yuli Ruan ,&nbsp;Rui Yang ,&nbsp;Xuefan Yu ,&nbsp;Yingjue Li ,&nbsp;Bojun Wang ,&nbsp;Yue Ma ,&nbsp;Feihong Chen ,&nbsp;Ruxin Xiong ,&nbsp;Yanqiao Zhang ,&nbsp;Chao Liu","doi":"10.1016/j.canlet.2025.217946","DOIUrl":"10.1016/j.canlet.2025.217946","url":null,"abstract":"<div><div>The tumor microenvironment of colorectal cancer (CRC) exhibits a highly immunosuppressive phenotype, contributing to resistance against immunotherapy and poor prognosis in patients. Lysine acetyltransferase 6A (KAT6A) is significant in immune regulation and advanced breast cancer treatment. However, its mechanistic involvement in regulating anti-tumor immune responses in CRC remains unclear. Using clinical CRC cohorts, we evaluated KAT6A expression levels and their clinical significance in this study. We investigated its functional role through subcutaneous and metastatic tumor models in mice. Our findings demonstrate that KAT6A is overexpressed in CRC and correlates with poor prognosis. Mass cytometry (CyTOF) and ATAC-seq analyses revealed that KAT6A knockdown enhanced CD8⁺ T cell infiltration by activating interferon (IFN) signaling pathways. Gene Set Enrichment Analysis (GSEA) and immunofluorescence assays confirmed that KAT6A knockdown activates the cGAS-STING pathway, subsequently inducing IFN-mediated immune responses. Mechanistically, knockdown of KAT6A relieves c-MYC/DNMT1-mediated repression of cGAS. We also evaluated the therapeutic effects of a KAT6A inhibitor alone and its combination with anti-PD-1 in microsatellite stable (MSS) and microsatellite instability-high (MSI-H) mouse models, demonstrating synergistic efficacy in combination therapy. Furthermore, in a cohort of CRC patients receiving immunotherapy, we showed that high KAT6A expression correlated with impaired treatment response, manifested by lower objective response rates, shorter progression-free survival (PFS), and decreased overall survival (OS). Importantly, this study reveals KAT6A's pivotal role in modulating CRC immune evasion via regulating endogenous IFN response of tumor cells, thereby establishing its potential as a therapeutic target for enhancing immunotherapy efficacy in CRC.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"631 ","pages":"Article 217946"},"PeriodicalIF":9.1,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144702364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DOT1L inhibition reprograms innate immunity to potentiate immunomodulatory drug responses in multiple myeloma","authors":"Kazuya Ishiguro ,&nbsp;Hiroshi Kitajima ,&nbsp;Takeshi Niinuma ,&nbsp;Reo Maruyama ,&nbsp;Tomohide Tsukahara ,&nbsp;Yoshihiko Hirohashi ,&nbsp;Akari Takaya ,&nbsp;Kohei Kumegawa ,&nbsp;Ayano Yoshido ,&nbsp;Shohei Sekiguchi ,&nbsp;Hajime Sasaki ,&nbsp;Akira Yorozu ,&nbsp;Mutsumi Toyota ,&nbsp;Masahiro Kai ,&nbsp;Toshihiko Torigoe ,&nbsp;Hiroshi Nakase ,&nbsp;Hiromu Suzuki","doi":"10.1016/j.canlet.2025.217941","DOIUrl":"10.1016/j.canlet.2025.217941","url":null,"abstract":"<div><div>Immunomodulatory drugs (IMiDs), such as lenalidomide, are a cornerstone of multiple myeloma (MM) treatment; however, their efficacy remains suboptimal. We previously reported that inhibition of DOT1L, a histone H3 lysine 79 methyltransferase, upregulates interferon (IFN)-regulated genes (IRGs) and exerts anti-MM effects. In this study, we aimed to further elucidate the epigenetic dependency of DOT1L in MM and the mechanism by which its inhibition induces innate immune signaling. Analysis of DepMap portal data revealed that MM cells are preferentially dependent on DOT1L, among epigenetic regulators, for survival. DOT1L inhibition activated type I IFN responses and increased expression of human leukocyte antigen (HLA) class II genes in MM cells. Notably, DOT1L inhibition was associated with induction of DNA damage responses. CRISPR/Cas9-mediated knockout of <em>STING1</em> attenuated IRG induction and diminished the anti-proliferative effects of DOT1L inhibition, suggesting that activation of STING signaling contributes to its anti-MM activity. Furthermore, DOT1L inhibition downregulated IKZF1/3 and IRF4, which was also associated with IRG induction. Finally, DOT1L inhibition enhanced the anti-MM efficacy of lenalidomide by further upregulating IRGs and suppressing IRF4-MYC signaling. These findings suggest that DOT1L is a preferential epigenetic therapeutic target in MM. Its inhibition not only activates innate immune signaling but also enhances the efficacy of lenalidomide.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"631 ","pages":"Article 217941"},"PeriodicalIF":9.1,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144685790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NSUN2-mediated m5C modification of KDM6B mRNA enhances osteoclast differentiation and promotes breast cancer bone metastasis","authors":"Ming Zhang ,&nbsp;Cheng Tang ,&nbsp;Shang Li ,&nbsp;Xinluan Jiang ,&nbsp;Bilan Li ,&nbsp;Yan Chen ,&nbsp;Que Zheng ,&nbsp;Yuting Tang ,&nbsp;Xiaoshu Zhu ,&nbsp;Lei Huang ,&nbsp;Hongyan Yuan ,&nbsp;Jue Wang ,&nbsp;Yongmei Yin ,&nbsp;Yucui Jin ,&nbsp;Changyan Ma","doi":"10.1016/j.canlet.2025.217939","DOIUrl":"10.1016/j.canlet.2025.217939","url":null,"abstract":"<div><div>Bone metastasis frequently occurs in advanced breast cancer (BCa) and is associated with poor prognosis. The pathogenesis of bone metastasis is driven by cross-communications within the tumor-bone microenvironment. In this study, we demonstrated that NSUN2, a 5-methylcytosine (m⁵C) methyltransferase, is significantly overexpressed in bone metastatic lesions of BCa compared to adjacent non-metastatic bone tissues. Overexpression of NSUN2 promoted osteoclast differentiation and osteolytic bone metastasis, whereas knockdown of NSUN2 had the opposite effects. Mechanistically, NSUN2 facilitates the degradation of lysine demethylase 6B (KDM6B) mRNA through m⁵C modification in a peptidylprolyl isomerase A (PPIA)-dependent manner. Reduced KDM6B leads to hypermethylation of NUMB, disrupting its interaction with the Notch1 intracellular domain (NICD1). Consequently, the Notch signaling pathway is activated, leading to upregulated RANKL expression and accelerated osteoclast differentiation, which contributes to osteolytic bone metastasis. Strikingly, activating KDM6B expression with paricalcitol or inhibiting the Notch pathway with DAPT effectively counteracted NSUN2-induced osteolytic bone metastasis <em>in vivo</em>. Collectively, our findings underscore the pivotal role of the NSUN2-KDM6B-Notch axis in promoting osteoclast differentiation and bone metastasis in BCa, providing potential therapeutic targets for BCa patients with bone metastasis.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"631 ","pages":"Article 217939"},"PeriodicalIF":9.1,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbiome and Gartynecologic Cancer.","authors":"Bingqing Liao, Liang Chen, Jinghan Ruan, Renjie Wang, Bai Hu, Rui Long, Yan Li, Guangmei Zhang, Jing Yu, Ming Zhang, Yuanzhen Zhang, Shujie Liao","doi":"10.1016/j.canlet.2025.217940","DOIUrl":"https://doi.org/10.1016/j.canlet.2025.217940","url":null,"abstract":"<p><p>In recent years more and more studies have pointed out that the microbiota plays an important role in the development of gynecological tumors. A healthy female reproductive tract microbiota is dominated by lactobacilli, which can produce lactic acid and other metabolites to protect the normal reproductive tract microenvironment. If the microflora is out of balance, the abnormally increased flora may contribute to inflammation and even cancer in the reproductive system by activating the immune response, regulating metabolites and hormone levels. In this review, we focus on the relationship between microbiota and three common gynecological cancers, namely cervical, endometrial and ovarian cancers, as well as the significance of microbes in the prevention, diagnosis, and treatment of these cancers, and we introduce the application of multi-omics techniques in microbes; finally, we analyze the common characteristics of microbes in gynecological cancers, and we propose the current challenges and future research directions.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"217940"},"PeriodicalIF":9.1,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Urinary exosomal FAM153C-RPL19 chimeric RNA as a diagnostic and prognostic biomarker for prostate cancer in Chinese patients","authors":"Bisheng Cheng ,&nbsp;Tianlong Luo ,&nbsp;Yongxin Wu ,&nbsp;Jintao Hu ,&nbsp;Chenwei Yang ,&nbsp;Jilin Wu ,&nbsp;Yong Luo ,&nbsp;WenTai Shangguan ,&nbsp;Weijia Li ,&nbsp;Lin Yang ,&nbsp;Wenxue Huang ,&nbsp;Cunzhen Ma ,&nbsp;Zhuohang Li ,&nbsp;Boyuan Sun ,&nbsp;Qiong Wang ,&nbsp;KeWei Xu ,&nbsp;Peng Wu ,&nbsp;Hai Huang","doi":"10.1016/j.canlet.2025.217938","DOIUrl":"10.1016/j.canlet.2025.217938","url":null,"abstract":"<div><div>Prostate cancer (PCa) is one of the most common malignancies in men, with an increasing incidence worldwide. Early detection is crucial for improving patient outcomes, yet the current biomarker, prostate-specific antigen (PSA), lacks sufficient specificity and sensitivity, especially in the diagnostic gray zone (PSA 4–10 ng/mL). Novel noninvasive biomarkers are needed to enhance diagnostic accuracy and reduce unnecessary biopsies. This study analyzed prostate cancer tissue, plasma, and urine samples from multiple cohorts, including the Chinese Prostate Cancer Genome Epigenome Atlas (CPGEA) dataset and external validation cohorts. RNA sequencing and qPCR validation were performed to assess the expression levels of FAM153C-RPL19 in urinary exosomes from PCa patients (n = 826), non-PCa individuals (n = 352), benign prostatic hyperplasia (BPH) patients (n = 396), and healthy controls (n = 428). Receiver operating characteristic (ROC) analysis was conducted to compare the diagnostic performance of FAM153C-RPL19 with PSA and PCA3. FAM153C-RPL19 levels were significantly higher in urinary exosomes of PCa patients than in healthy, BPH, and non-PCa controls. Higher levels correlated with advanced stages (Stage III–IV) and Gleason scores (GS ≥ 7). Urinary exosomal FAM153C-RPL19 outperformed plasma exosomes as a diagnostic marker. It showed superior diagnostic accuracy (AUC = 0.93) over PSA (AUC = 0.81), especially in PSA gray-zone cases (AUC = 0.92). Higher levels were associated with poor prognosis (HR = 2.95, 95 % CI: 1.90–4.58). Combining FAM153C-RPL19 with PSA and PCA3 improved diagnostic performance (AUC = 0.97). These findings suggest that urinary exosomal FAM153C-RPL19 is a promising noninvasive biomarker for prostate cancer detection and risk stratification, with higher specificity and sensitivity than PSA, particularly in the diagnostic gray zone. Its strong correlation with disease progression and prognosis further supports its potential clinical utility in liquid biopsy-based PCa screening.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"631 ","pages":"Article 217938"},"PeriodicalIF":9.1,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}