Translational Oncology最新文献

{"title":"Therapeutic advances and application of PARP inhibitors in breast cancer","authors":"Teng Zhou ,&nbsp;Jian Zhang","doi":"10.1016/j.tranon.2025.102410","DOIUrl":"10.1016/j.tranon.2025.102410","url":null,"abstract":"<div><div>Targeting of DNA repair pathway is the main therapeutic approach for BRCA1 and BRCA2 associated tumors, including breast cancer. BRCA1/2 genes play a pivotal role in HRR pathway. Mutations in BRCA1/2 leads to DDR deficiency, which cause the increasing of genome instability, thus rendering cancer cells vulnerable to inhibition of DNA repair related proteins, such as PARP1. Pre-clinical studies has demonstrated that cancer cells with BRCA1/2 deficient are sensitive to PARPi, which are an emerging class of small molecule drug. Several clinical trials demonstrated the promising efficacy of PARP inhibitors for BRCA1/2 mutated breast cancer patient through selectively induce synthetic lethality cancer cells. Currently, four PARP inhibitors had been approved by FDA for clinical use. PARPi demonstrated to improve progression-free survival, while resistance to PARPi is inevitable. In this review article, we highlighted the advances in the PARPi clinical trials, resistance mechanism and coping strategies in breast cancer patients. We also summarized the international guideline and recommendations on PARP inhibitor usage in breast cancer.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"57 ","pages":"Article 102410"},"PeriodicalIF":5.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143936289","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":"LMO2 confers value as a potential immunotherapy marker in pan-cancer analysis and inhibits progression of Clear Cell Renal Cell Carcinoma","authors":"Huiping Wang ,&nbsp;Cong Wang ,&nbsp;Jia Wei ,&nbsp;Xuan’er Zhao ,&nbsp;Xuemei Yang ,&nbsp;Renren Li ,&nbsp;Mengmeng Li ,&nbsp;Zhansheng Zhu","doi":"10.1016/j.tranon.2025.102409","DOIUrl":"10.1016/j.tranon.2025.102409","url":null,"abstract":"<div><h3>Background</h3><div>Emerging evidence highlights LIM-domain only 2 (LMO2) as both a potential biomarker and therapeutic target in diverse cancers. However, its functional characterization and clinical significance remain insufficiently explored in cancers such as Clear Cell Renal Cell Carcinoma (ccRCC). Therefore, comprehensive pan-cancer analysis and mechanistic investigation are necessary for optimizing LMO2-targeted immunotherapy strategies.</div></div><div><h3>Methods</h3><div>We conducted comprehensive multi-omics analyses and clinicopathological correlation studies across all cancers using TCGA data and specialized bioinformatics tools. Immune microenvironment associations were evaluated through Pearson correlation coefficients and TIMER algorithm validation. Subsequent functional enrichment analyses and predictive regulator identification were performed to delineate signaling pathways in ccRCC. Mechanistic insights were validated through in vitro models and xenograft experiments.</div></div><div><h3>Results</h3><div>LMO2 demonstrates significant deregulation across multiple malignancies, with its mRNA expression exhibiting distinct correlations with clinical staging, survival outcomes, and tumor immune microenvironment characteristics. Systematic analysis further confirmed it as a potentially novel immunotherapeutic target. Mechanistic investigations revealed that ZC3H13 depletion mediates LMO2 downregulation through N6-methyladenosine (m6A)-dependent epigenetic modifications. Through comprehensive functional validation in ccRCC, we established LMO2′s tumor-suppressive properties using both in vitro models and xenograft assays. Subsequent pathway investigation demonstrated that LMO2 exerts its anti-tumor effects through direct modulation of the NF-κB signaling cascade via the GATA2-BEX1 regulatory axis.</div></div><div><h3>Conclusions</h3><div>Our findings establish substantial evidence for LMO2 as both a potential therapeutic candidate in cancer immunotherapy and a significant prognostic modulator in ccRCC pathogenesis. The mechanistic characterization of LMO2′s tumor-suppressive functions warrants heightened translational consideration in both clinical management strategies and molecular etiology research.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"57 ","pages":"Article 102409"},"PeriodicalIF":5.0,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143929580","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":"Molecular characterisation of the residual disease after neoadjuvant endocrine therapy in ER+/HER2- breast cancer uncovers biomarkers of tumour response","authors":"Joanna I. López-Velazco ,&nbsp;Sara Manzano ,&nbsp;Kepa Elorriaga ,&nbsp;Maria Otaño ,&nbsp;Ainhara Lahuerta ,&nbsp;Luis Álvarez ,&nbsp;Inge Etxabe ,&nbsp;Miren Huarte ,&nbsp;Elvira Buch ,&nbsp;Julia Gimenez ,&nbsp;Vanesa Quiroga ,&nbsp;Marta Fernandez ,&nbsp;Sofía Aragón ,&nbsp;Laia Paré ,&nbsp;Aleix Prat ,&nbsp;Isabel Álvarez-López ,&nbsp;Maria M. Caffarel ,&nbsp;Ander Urruticoechea","doi":"10.1016/j.tranon.2025.102407","DOIUrl":"10.1016/j.tranon.2025.102407","url":null,"abstract":"<div><h3>Background</h3><div>Neoadjuvant endocrine therapy (NET) in oestrogen receptor-positive /HER2-negative breast cancer (ER+/HER2- BC) allows real-time evaluation of treatment sensitivity by monitoring tumour response and offers the opportunity of personalised therapy. However, the lack of reproducible biomarkers to assess response and long-term prognosis after NET is a significant barrier to increase its indications.</div></div><div><h3>Methods</h3><div>In this study we searched for clinically relevant molecular reporters of response to NET in a multicentre population of ER+/HER2- BC patients (<em>n</em> = 87) by using: PAM50 gene expression panel and immunohistochemical evaluation of key proteins involved in tumorigenesis.</div></div><div><h3>Results</h3><div>Our PAM50 analyses show that tumours changing from luminal A to normal-like subtype after NET presented better radiological and pathological tumour responses, a significant larger decrease in Ki67 at surgery, lower preoperative endocrine prognostic index score (PEPI) and lower tumour cellularity size (TCS) than those with persistent luminal A status. Patients with the highest response to NET showed the largest decrease in PAM50-derived risk of recurrence (ROR) following NET. In addition, the percentage of p53 positive cells was associated with decreased response to NET.</div></div><div><h3>Conclusions</h3><div>Our findings highlight the change of intrinsic subtype from luminal A to normal-like after NET as a putative biomarker characterising the patient population that obtains the highest benefit from NET. Our study also suggests that changes in PAM50-derived ROR score and p53 evaluation could also help to identify those patients. Thus, this study uncovers potential biomarkers of response to NET and prognosis, which should be validated in independent cohorts, helping to the implementation of NET in the clinical practice.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"57 ","pages":"Article 102407"},"PeriodicalIF":5.0,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143929040","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":"Single-Cell and Single-Nuclei transcriptomics profiling reveals dynamic cellular features in tumor-related adipose microenvironment of breast cancer patients with high BMI","authors":"Xiaoxiao Hu ,&nbsp;Fang Jia ,&nbsp;Lili Li ,&nbsp;Wuzhen Chen ,&nbsp;Leyi Zhang ,&nbsp;Jun Pan ,&nbsp;Sangsang Zhu ,&nbsp;Zhen Wang ,&nbsp;Jian Huang","doi":"10.1016/j.tranon.2025.102408","DOIUrl":"10.1016/j.tranon.2025.102408","url":null,"abstract":"<div><h3>Objectives</h3><div>High body mass index (BMI), encompassing overweight and obesity, is a well-established risk factor for developing breast cancer (BC). The underlying mechanisms linking elevated BMI to increased BC risk involve metabolic reprogramming and chronic inflammatory microenvironments regulated by cellular networks within breast white adipose tissue (WAT). However, the complicated landscape and specific cell chat leading to BC-related adipose microenvironment remained unclear.</div></div><div><h3>Materials and methods</h3><div>We unveiled a comprehensive cell atlas by employing single-cell (<em>N</em> = 27) and single-nuclei (<em>N</em> = 6) transcriptomics to address dynamic changes of immune and stromal cell components within WAT in high BMI population. Bulk RNA-seq data sets were used for validation.</div></div><div><h3>Results</h3><div>Characteristics of adipose-infiltrating tissue-resident macrophages (PVMs), APOD+γδ T cells, and mature FKBP5+ adipocytes in breast cancer women with high BMI were revealed, in terms of transcriptional genes, metabolism features, developmental trajectories and gene set enrichment analysis (GSEA). PVMs upregulated c-Maf combined with its co-activator CREB1 to increase TCA cycles. APOD+γδ T cells were found to elevate intracellular lipid metabolism, leading to poor clinical prognosis. Mature FKBP5+adipocytes served as an advanced adipogenesis mediator to promote tumor aggressiveness. In-depth analysis of cell-cell interactions uncovered a remodeling trend towards metabolic dysfunction and chronic inflammation in WAT with weight gain via EGF, CXCL, and CCL signalings.</div></div><div><h3>Conclusion</h3><div>These results provided a novel understanding of detailed and unbiased cellular landscape of WAT in breast cancer with high BMI from single-cell atlas perspective, uncovering interplays between breast adipose-infiltrating immune cells and stromal cells that promote progression of BC under high BMI conditions.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"57 ","pages":"Article 102408"},"PeriodicalIF":5.0,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143929039","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":"Estrogen inhibits hepatocellular carcinoma progression dependent on HOXA11-AS/HOXA11","authors":"Pincheng Zhou ,&nbsp;Fengze Sun ,&nbsp;Peixu Lin ,&nbsp;Yan Yan ,&nbsp;Jiayao Liu ,&nbsp;Yang Zhou ,&nbsp;Ting He ,&nbsp;Pengcheng Liu ,&nbsp;Jie Wang ,&nbsp;Huanhuan Sun ,&nbsp;Haiqing Ma","doi":"10.1016/j.tranon.2025.102404","DOIUrl":"10.1016/j.tranon.2025.102404","url":null,"abstract":"<div><h3>Background</h3><div>The role of estrogen in liver cancer cells has attracted attention, but its specific actions and underlying mechanisms remain unclear.</div></div><div><h3>Methods</h3><div>Flow CytoMetry and Western blotting were used to investigate the mechanism of HOXA11-AS and estrogen in promoting apoptosis of hepatocellular carcinoma (HCC). In vivo subcutaneous tumorigenesis assays were uesd to confirm the regulatory role of HOXA11-AS in HCC progression. Through immunohistochemistry, the correlation between HOXA11 expression and the prognosis of patients with HCC was explored.</div></div><div><h3>Results</h3><div>Estrogen was found to promote apoptosis in HCC cells, dependent on HOXA11-AS. HOXA11 and HOXA11-AS are upregulated in HCC tissues. Downregulation of HOXA11-AS and HOXA11 significantly inhibited cell proliferation, migration, and invasion in HCC. HOXA11-AS forms an RNA duplex with HOXA11, preventing RNase degradation. In HCC patients, high HOXA11 expression was significantly associated with lower overall survival (OS) (<em>p</em>=0.001) and disease-free survival (DFS) (<em>p</em>=0.002). High HOXA11 expression was also significantly correlated with recurrence (<em>p</em>&lt;0.001), major vascular invasion (<em>p</em>=0.002) and increased tumor volume (<em>p</em>=0.007). Estrogen activated the c-met/AKT/mTOR pathway in the HCC cell line.</div></div><div><h3>Conclusion</h3><div>Estrogen and its related proteins have therapeutic effects in HCC and may be new potential therapeutic targets.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"57 ","pages":"Article 102404"},"PeriodicalIF":5.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143916207","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":"Investigating the molecular mechanisms and clinical potential of APO+ endothelial cells associated with PANoptosis in the tumor microenvironment of hepatocellular carcinoma using single-cell sequencing data","authors":"Zhaorui Cheng ,&nbsp;Xiangyu Yang ,&nbsp;Yi Ren ,&nbsp;Huimin Wang ,&nbsp;Qi Zhang ,&nbsp;Sailing Lin ,&nbsp;Wenhao Wu ,&nbsp;Xiaolu Yang ,&nbsp;Jiahan Zheng ,&nbsp;Xinzhu Liu ,&nbsp;Xin Tao ,&nbsp;Xiaoyong Chen ,&nbsp;Yuxin Qian ,&nbsp;Xiushen Li","doi":"10.1016/j.tranon.2025.102402","DOIUrl":"10.1016/j.tranon.2025.102402","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;PANoptosis is a newly identified form of programmed cell death that integrates elements of pyroptosis, apoptosis, and necroptosis. It plays a pivotal role in shaping the tumor immune microenvironment. Despite its significance, the specific functions and mechanisms of PANoptosis within the tumor microenvironment (TME) of hepatocellular carcinoma (HCC) remain unclear. This study aims to investigate these mechanisms using single-cell RNA sequencing data.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Single-cell RNA sequencing data from HCC patients were obtained from the GEO database. The AUCell algorithm was used to quantify PANoptosis activity across various cell types in the TME. Cell populations with high PANoptosis scores were further analyzed using CytoTRACE and scMetabolism to assess their differentiation states and metabolic profiles. Associations between these high-score cell subsets and patient prognosis, tumor stage, and response to immunotherapy were examined. Cell-cell communication analysis was performed to explore how PANoptosis-related APO+ endothelial cells (ECs) may influence HCC progression. Immunofluorescence staining was used to assess the spatial distribution of APO+ ECs in tumor and adjacent tissues. Finally, a CCK8 assay was conducted to evaluate the effect of APOH+ HUVECs on HCC cell proliferation.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;A total of 16 HCC patient samples with single-cell RNA sequencing data were included in the study. By calculating the PANoptosis scores of different cell types, we found that ECs, macrophages, hepatocytes, and fibroblasts exhibited higher PANoptosis scores. The PANoptosis scores, differentiation trajectories, intercellular communication, and metabolic characteristics of these four cell subpopulations with high PANoptosis scores were visualized. Among all subpopulations, APO+ ECs demonstrated the most significant clinical relevance, showing a positive correlation with better clinical staging, prognosis, and response to immunotherapy in HCC patients. Cellular communication analysis further revealed that APO+ ECs might regulate the expression of HLA molecules, thereby influencing T cell proliferation and differentiation, potentially contributing to improved prognosis in HCC patients. Immunofluorescence staining results indicated that APO+ ECs were primarily located in the adjacent tissues of HCC patients, with lower expression in tumor tissues. The results of cellular experiments showed that APOH+ HUVECs significantly inhibited the proliferation of HCC cells.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;This study systematically mapped the cellular landscape of the TME in HCC patients and explored the differences in differentiation trajectories, metabolic pathways, and other aspects of subpopulations with high PANoptosis scores. Additionally, the study elucidated the potential molecular mechanisms through which APO+ ECs inhibit HCC cell proliferation and improve prognosis and imm","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"57 ","pages":"Article 102402"},"PeriodicalIF":5.0,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143898397","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":"Carfilzomib promotes Iodine-125 seed radiation-induced apoptosis, paraptosis, and ferroptosis in esophageal squamous cell carcinoma by aggravating endoplasmic reticulum stress","authors":"Chao Wang ,&nbsp;Yin-Lin Zha ,&nbsp;Hao Wang ,&nbsp;Bai Sun ,&nbsp;Wei-Guang Qiang ,&nbsp;Ye Yuan ,&nbsp;Hong-Bing Shi ,&nbsp;Wen-Wei Hu","doi":"10.1016/j.tranon.2025.102393","DOIUrl":"10.1016/j.tranon.2025.102393","url":null,"abstract":"<div><div>Iodine-125 (¹²⁵I) seed brachytherapy has been applied to treat various malignant tumors such as esophageal cancer, however, radioresistance can reduce its efficacy. Endoplasmic reticulum stress (ERS) and subsequent unfolded protein response (UPR) is one of the core mechanisms of ¹²⁵I seed radiation-induced cell death, thus aggravating ERS has been considered a promising sensitization strategy. Herein, we show that combination therapy of an irreversible proteasome inhibitor carfilzomib (CFZ) and ¹²⁵I seed radiation displayed strong anti-tumor effect on esophageal squamous cell carcinoma (ESCC). Mechanistically, ERS and UPR regulated multiple cell death modalities induced by the combination therapy, including apoptosis, paraptosis, and ferroptosis. ¹²⁵I seed radiation induced reactive oxygen species (ROS) production, DNA damage, p53 activation, and apoptosis. CFZ promoted ROS production, and augmented ¹²⁵I seed radiation-induced apoptosis via the mitochondrial pathway, which was mediated by the UPR-C/EBP homologous protein (CHOP) pathway and was independent of the p53 pathway. CFZ enhanced ¹²⁵I seed radiation-induced intracellular Ca²⁺ overload, protein ubiquitination, ERS, and UPR, consequently promoting paraptosis. ¹²⁵I seed radiation induced accumulation of intracellular Fe²⁺ and lipid peroxides but upregulated the expression of ferroptosis inhibitors, SLC7A11 and glutathione peroxidase 4 (GPX4). The combination therapy promoted ferroptosis by enhancing the accumulation of intracellular Fe²⁺ and downregulating GPX4 expression. The mouse experiment demonstrated that CFZ can promote the efficacy of ¹²⁵I seed radiation with good tolerance. Our findings suggest that combination therapy of ¹²⁵I seed radiation and CFZ is associated with multiple cell death modalities and may serve as a promising therapeutic strategy for ESCC.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"57 ","pages":"Article 102393"},"PeriodicalIF":5.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143895920","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":"Identification and external validation of tumor DNA methylation panel for the recurrence risk stratification of stage II colon cancer","authors":"Tanwei Yuan ,&nbsp;Dominic Edelmann ,&nbsp;Víctor Moreno ,&nbsp;Elisabeth Georgii ,&nbsp;Lisa Barros de Andrade e Sousa ,&nbsp;Helena Pelin ,&nbsp;Xiaofeng Jiang ,&nbsp;Jakob Nikolas Kather ,&nbsp;Katrin E. Tagscherer ,&nbsp;Wilfried Roth ,&nbsp;Melanie Bewerunge-Hudler ,&nbsp;Alexander Brobeil ,&nbsp;Matthias Kloor ,&nbsp;Hendrik Bläker ,&nbsp;Hermann Brenner ,&nbsp;Michael Hoffmeister","doi":"10.1016/j.tranon.2025.102405","DOIUrl":"10.1016/j.tranon.2025.102405","url":null,"abstract":"<div><h3>Background</h3><div>Tailoring surveillance and treatment strategies for stage II colon cancer (CC) after curative surgery remains challenging, and personalized approaches are lacking. We aimed to identify a gene methylation panel capable of stratifying high-risk stage II CC patients for recurrence beyond traditional clinical variables.</div></div><div><h3>Methods</h3><div>Genome-wide tumor tissue DNA methylation data were analyzed from 562 stage II CC patients who underwent surgery in Germany (DACHS study). The cohort was divided into a training set (<em>N</em> = 395) and an internal validation set (<em>N</em> = 131), with external validation performed on 97 stage II CC patients from Spain. DNA methylation markers were primarily selected using the Elastic Net Cox model. The resulting prognostic index (PI), a combination of clinical factors and selected methylation markers, was compared to baseline models using clinical variables or microsatellite instability (MSI), with discrimination and prediction accuracy assessed through time-dependent receiver operating characteristic curves (AUC) and Brier scores.</div></div><div><h3>Results</h3><div>The final PI incorporated age, sex, tumor stage, location, and 27 DNA methylation markers. The PI consistently outperformed the baseline model including age, sex, and tumor stage in time-dependent AUC across validation cohorts (e.g., 1-year AUC and 95 % confidence interval: internal validation set, PI: 0.66, baseline model: 0.52; external validation set, PI: 0.72, baseline model: 0.64). In internal validation, the PI also showed a consistently improved time-dependent AUC compared with a combination of MSI and tumor stage only. Nevertheless, the PI did not improve the prediction accuracy of CC recurrence compared to the baseline model.</div></div><div><h3>Conclusions</h3><div>This study identified 27 tumor tissue DNA methylation biomarkers that improved the discriminative power in classifying recurrence risk among stage II colon cancer patients. While this methylation panel alone lacks sufficient prediction accuracy for clinical application, its discriminative improvement suggests potential value as part of a multimodal risk-stratification tool.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"57 ","pages":"Article 102405"},"PeriodicalIF":5.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143891654","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":"miR-4537 curtails ferroptosis by targeting MIOX in renal cell carcinoma","authors":"Hui Li ,&nbsp;Mengyu Fu ,&nbsp;Lingli Wang ,&nbsp;Yanpeng Dai ,&nbsp;Zongxing Lv ,&nbsp;Shilin Geng","doi":"10.1016/j.tranon.2025.102401","DOIUrl":"10.1016/j.tranon.2025.102401","url":null,"abstract":"<div><div>Ferroptosis, an iron-dependent mode of cell death, has gained prominence for its critical role in the advancement of various cancers, notably clear cell renal carcinoma (ccRCC). The intricacies of ferroptosis’s involvement in ccRCC, however, remain largely undefined. This study aimed to dissect the contribution of ferroptosis to ccRCC by examining differentially expressed genes (DEGs) identified within the TCGA ccRCC database and ferroptosis driver genes catalogued in the FerrDb database (dedicates to ferroptosis regulators and ferroptosis-disease associations). We employed 786-O and ACHN ccRCC cell lines, alongside HK2 (human kidey-2) cells and HKC (human kidney cells), to confirm the expression of 9 shared genes. Among these, MIOX (myo-inositol oxygenase) emerged as significantly downregulated in ccRCC cells compared to HK2 and HKC cells. Subsequent survival analysis illuminated a positive correlation between MIOX expression and improved patient survival, underscoring its prognostic significance. Further investigations into MIOX regulation identified four miRNAs via TargetScan predictions, with miR-4537 significantly upregulated in ccRCC cell lines. Functional assays involving miR-4537 mimics and inhibitors, combined with ferroptosis inducers and inhibitors, elucidated its impact on ccRCC cell growth and ferroptosis modulation. The results revealed that miR-4537 expression was diminished following ferroptosis induction, and the miR-4537 inhibitor markedly curbing ccRCC cell proliferation by fostering ferroptosis, while the mimic exerted opposite effects. Mechanistically, miR-4537 targets the 3′-UTR of MIOX to manipulate its expression, ultimately inhibiting ferroptosis in ccRCC cells. Our research indicated that miR-4537 restrained ferroptosis by regulating MIOX in ccRCC, offering novel insights into the mechanisms of ferroptosis in cancer biology and highlighting latent therapeutic avenues for cancer treatment through ferroptosis modulation.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"56 ","pages":"Article 102401"},"PeriodicalIF":5.0,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886434","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":"In vivo inhibition of angiogenesis by htsFLT01/MiRGD nano complex","authors":"Mohadeseh Khoshandam ,&nbsp;Zahra-Soheila Soheili ,&nbsp;Saman Hosseinkhani ,&nbsp;Shahram Samiee ,&nbsp;Hamid Latifi-Navid ,&nbsp;Hamid Ahmadieh ,&nbsp;Hossein Soltaninejad ,&nbsp;Babak Jahangiri","doi":"10.1016/j.tranon.2025.102400","DOIUrl":"10.1016/j.tranon.2025.102400","url":null,"abstract":"<div><div>The inhibition of angiogenesis is a crucial therapeutic strategy in cancer treatment, as it limits tumor growth and metastasis. In this study, we investigate the anti-angiogenic potential of a novel htsFLT01/MiRGD nanocomplex, designed to target key angiogenesis markers in cancer. This nanocomplex integrates the anti-angiogenic fusion protein htsFLT01 with the MiRGD peptide to enhance its efficacy. Our findings demonstrate that htsFLT01/MiRGD effectively suppresses angiogenesis both in vitro and in vivo, particularly in breast cancer models. Histological and molecular analyses reveal a significant reduction in blood vessel formation, accompanied by structural changes in tumor tissue. Furthermore, the expression levels of key angiogenesis-related genes, including VEGF, VEGFR, and CD31, are markedly downregulated, highlighting the therapeutic potential of this nanocomplex. Beyond its anti-angiogenic effects, the treatment also induces apoptosis and inhibits tumor cell proliferation, reinforcing its role as a promising targeted therapy for angiogenesis-dependent malignancies. These results underscore the potential of htsFLT01/MiRGD in cancer treatment and pave the way for future clinical applications in anti-angiogenic therapies.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"56 ","pages":"Article 102400"},"PeriodicalIF":5.0,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143881566","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}