Translational cancer research最新文献

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MIF-mediated intercellular crosstalk drives antigen-presenting-like cancer-associated fibroblast differentiation in triple-negative breast cancer via TGF-β signaling. mif介导的细胞间串扰通过TGF-β信号传导驱动三阴性乳腺癌抗原呈递样癌相关成纤维细胞分化。
IF 2.1 4区 医学
Translational cancer research Pub Date : 2026-09-30 Epub Date: 2026-08-24 DOI: 10.21037/tcr-2026-1747
Jun Wang, Yeru Li, Jia Zhu, Dan Ruan, Xinchang Xu, Wei Wang
{"title":"MIF-mediated intercellular crosstalk drives antigen-presenting-like cancer-associated fibroblast differentiation in triple-negative breast cancer via TGF-β signaling.","authors":"Jun Wang, Yeru Li, Jia Zhu, Dan Ruan, Xinchang Xu, Wei Wang","doi":"10.21037/tcr-2026-1747","DOIUrl":"https://doi.org/10.21037/tcr-2026-1747","url":null,"abstract":"<p><strong>Background: </strong>Triple-negative breast cancer (TNBC) is characterized by an aggressive tumor microenvironment (TME) in which cancer-associated fibroblasts (CAFs) play a pivotal role. However, the molecular mechanisms governing the transformation of quiescent fibroblasts into distinct CAF subtypes within TNBC remain poorly understood. This study aimed to elucidate the molecular mechanisms underlying fibroblast-to-CAF subtype transition in TNBC and identify key signaling pathways involved in TNBC-driven CAF activation.</p><p><strong>Methods: </strong>Transcriptomic data from The Cancer Genome Atlas (TCGA)-TNBC were analyzed using weighted gene co-expression network analysis (WGCNA). CAF-related scores and TNBC scores were computed via single-sample gene set enrichment analysis (ssGSEA). CAF infiltration was assessed using Estimating the Proportion of Immune and Cancer cells (EPIC). Survival and correlation analyses were validated in the Gene Expression Omnibus (GEO) dataset GSE58812. Single-cell RNA sequencing (scRNA-seq) data (GSE176078) were employed for cell-type annotation, pseudotime trajectory inference, and cell-cell communication analysis. Cell experiments were further performed to explore the mechanisms of fibroblast activation in TNBC.</p><p><strong>Results: </strong>TNBC score was significantly associated with poor prognosis and positively correlated with CAF score/infiltration. Single-cell analysis revealed antigen-presenting CAFs (apCAFs) as the predominant CAF subtype in TNBC. Pseudotime trajectory analysis showed that 96 genes uniquely involved in quiescent-to-apCAF-like differentiation were enriched in TGF-β signaling. Cell-cell communication analysis identified macrophage migration inhibitory factor (MIF)-(CD74 + CXCR4) as significantly enhanced during TNBC-apCAF interactions but absent in TNBC-myofibroblastic CAF (myCAF) crosstalk. Four hub genes, including <i>CNTN4</i>, <i>NLGN1</i>, <i>NLGN4X</i>, and <i>SEMA5A</i>, were identified as associated with the differentiation stage: <i>CNTN4</i>/<i>NLGN1</i> in MIF-mediated signal initiation and <i>NLGN4X</i>/<i>SEMA5A</i> in the intracellular TGF-β execution phase. Cell experiments revealed that the MIF-CD74/CXCR4 axis promotes apCAF-like differentiation via the TGF-β pathway and enhances malignant phenotypes of TNBC cells.</p><p><strong>Conclusions: </strong>A TNBC-to-apCAF signaling axis was identified wherein TNBC-secreted MIF activates CD74/CXCR4 on fibroblasts, engaging TGF-β signaling to drive apCAF-like differentiation. These findings offer potential therapeutic targets for disrupting the pro-tumorigenic microenvironment in TNBC.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 9","pages":"690"},"PeriodicalIF":2.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A novel three-CpG signature for lung adenocarcinoma diagnosis: integrating multi-omics, machine learning, and clinical validation. 一种用于肺腺癌诊断的新型三cpg特征:整合多组学、机器学习和临床验证。
IF 2.1 4区 医学
Translational cancer research Pub Date : 2026-09-30 Epub Date: 2026-09-24 DOI: 10.21037/tcr-2026-2178
Qianying Liu, Maoting Shen, Lirui Yan, Yongfeng Li, Yi Wang, Junzhe Li, Shuyun Xiong, Jiamin Liao, Weikang Li, Yujuan Xiong, Ji-Cai Chen
{"title":"A novel three-CpG signature for lung adenocarcinoma diagnosis: integrating multi-omics, machine learning, and clinical validation.","authors":"Qianying Liu, Maoting Shen, Lirui Yan, Yongfeng Li, Yi Wang, Junzhe Li, Shuyun Xiong, Jiamin Liao, Weikang Li, Yujuan Xiong, Ji-Cai Chen","doi":"10.21037/tcr-2026-2178","DOIUrl":"https://doi.org/10.21037/tcr-2026-2178","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Lung adenocarcinoma (LUAD) is a leading cause of cancer-related mortality worldwide. The identification of non-invasive biomarkers for early detection is critical to improving patient outcomes. Integrative analysis of DNA methylation and gene expression represents a promising approach for identifying cancer-specific diagnostic markers. This study aimed to identify and validate a LUAD-specific DNA methylation signature for the early detection of LUAD.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;An integrated analysis of DNA methylation data from the Illumina HumanMethylation450K array, including 455 tumor samples, 32 normal samples, and RNA-sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA) LUAD cohort was performed. Differential methylation and expression were identified, and LUAD-specific markers were selected by excluding probes altered in 10 other cancer types. All combinations of five candidate cytosine-phosphate-guanine (CpG) sites (excluding single-site combinations) were constructed using four machine learning algorithms, generating 104 models. A stringent two-step filtering strategy required each model to achieve an area under the curve (AUC) &gt;0.8, F1 score &gt;0.8, and coefficient of variation (CV) &lt;0.1 in at least four of the five validation datasets [including TCGA test set and four independent Gene Expression Omnibus (GEO) cohorts] and required each CpG combination to be validated by all four algorithms. Candidate methylation markers were experimentally validated by MethyLight quantitative polymerase chain reaction (qPCR) in 97 paired LUAD and 14 benign lung lesion samples.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;We identified 6,840 differentially methylated sites (DMSs) and 3,020 differentially expressed genes (DEGs). Integration of multi-omics data revealed 132 genes with correlated methylation-expression patterns. After filtering for LUAD specificity, 36 methylation markers were retained. A three-CpG eXtreme Gradient Boosting (XGBoost) model (cg00817598 in &lt;i&gt;WNT3&lt;/i&gt;, cg13470063 in &lt;i&gt;TIE1&lt;/i&gt;, and cg23094674 in &lt;i&gt;PLEKHA6&lt;/i&gt;) was selected as the optimal classifier, achieving an AUC of 0.995 in TCGA test set and AUC values ranging from 0.864 to 0.986 across the four GEO datasets. The model demonstrated robust cancer-type specificity (AUC: 0.771 in distinguishing LUAD from 565 other cancer samples) and outperformed established markers &lt;i&gt;RASSF1A&lt;/i&gt; and &lt;i&gt;SHOX2&lt;/i&gt; (average AUC: 0.725-0.937). Experimental validation confirmed significant hypermethylation of all three CpG sites in LUAD tissues (all P&lt;0.001). The model achieved an AUC of 0.832 in distinguishing LUAD from benign lesions. Methylation levels of cg23094674 and cg00817598 showed positive correlations with tumor size and progressively increased from benign lesions to early-stage and advanced LUAD.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;A three-CpG methylation signature was identified that may serve as a highly specific and sensitive diagnostic biomarker ","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 9","pages":"715"},"PeriodicalIF":2.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Adjuvant management of resectable stage III/IV melanoma. 可切除的III/IV期黑色素瘤的辅助治疗。
IF 2.1 4区 医学
Translational cancer research Pub Date : 2026-09-30 Epub Date: 2026-09-21 DOI: 10.21037/tcr-2026-1744
Nicole Flores, Matthew J Hadfield
{"title":"Adjuvant management of resectable stage III/IV melanoma.","authors":"Nicole Flores, Matthew J Hadfield","doi":"10.21037/tcr-2026-1744","DOIUrl":"https://doi.org/10.21037/tcr-2026-1744","url":null,"abstract":"","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 9","pages":"721"},"PeriodicalIF":2.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Analysis and validation of prognostic markers for thyroid cancer by single-cell and bulk RNA sequencing. 单细胞和大量RNA测序对甲状腺癌预后标志物的分析和验证。
IF 2.1 4区 医学
Translational cancer research Pub Date : 2026-09-30 Epub Date: 2026-08-24 DOI: 10.21037/tcr-2026-1398
Yang Yang, Liufei Yang, Xianfeng Jiang
{"title":"Analysis and validation of prognostic markers for thyroid cancer by single-cell and bulk RNA sequencing.","authors":"Yang Yang, Liufei Yang, Xianfeng Jiang","doi":"10.21037/tcr-2026-1398","DOIUrl":"https://doi.org/10.21037/tcr-2026-1398","url":null,"abstract":"<p><strong>Background: </strong>Thyroid cancer represents the most prevalent malignancy within the endocrine system, exhibiting consistent increasing incidence rates over the years. We aim to utilize single-cell RNA sequencing (scRNA-seq) dataset to analyze key genes associated with prognosis in thyroid cancer.</p><p><strong>Methods: </strong>Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were applied to detect thyroid cell-related genes in the paratumor and tumor groups. Least absolute shrinkage and selection operator (LASSO) analysis was conducted on The Cancer Genome Atlas (TCGA) data to identify key genes and develop prognostic models. Immune infiltration analysis, correlation analysis, and differential expression analysis were used to explore the immunological features, correlation, and expression levels of the characterized genes. Western blot and immunohistochemical staining experiments were used to further validate the expression patterns of the characterized genes.</p><p><strong>Results: </strong>A total of 3,681 differentially expressed genes (DEGs) were recognized. There were 157 genes derived from the key modules in the WGCNA analysis. By performing intersection and conducting LASSO analysis, a prognostic model was developed based on the expression levels of six signature genes (<i>APOE</i>, <i>MDK</i>, <i>NPC2</i>, <i>FCGBP</i>, <i>GLUL</i>, and <i>DTX4</i>). The model's applicability was confirmed using the Gene Expression Omnibus (GEO) validation set. Immune infiltration analysis revealed varying degrees of immune cell infiltration between the high- and low-risk groups, which were intimately associated with the characterized genes. Subsequent experiments confirmed that APOE, MDK, and NPC2 protein levels were significantly higher in the thyroid cancer group compared to the control group.</p><p><strong>Conclusions: </strong><i>APOE</i>, <i>MDK</i>, <i>NPC2</i>, <i>FCGBP</i>, <i>GLUL</i>, and <i>DTX4</i> may be key genes in thyroid cancer progression and serve as potential targets for disease treatment.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 9","pages":"691"},"PeriodicalIF":2.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
PM2.5 promotes migration of hepatocellular carcinoma by targeting miR-25. PM2.5通过靶向miR-25促进肝癌的迁移。
IF 2.1 4区 医学
Translational cancer research Pub Date : 2026-09-30 Epub Date: 2026-08-17 DOI: 10.21037/tcr-2026-0728
Qiaoxin Li, Yuxuan Lu, Quanyu Guo, Tianle Jin, Le Lu, Hao Shang, Meng Fan, Jiantao Mo, Hua Zhang, Wanying Feng, Xuanbo Da, Hongwei Lu
{"title":"PM2.5 promotes migration of hepatocellular carcinoma by targeting miR-25.","authors":"Qiaoxin Li, Yuxuan Lu, Quanyu Guo, Tianle Jin, Le Lu, Hao Shang, Meng Fan, Jiantao Mo, Hua Zhang, Wanying Feng, Xuanbo Da, Hongwei Lu","doi":"10.21037/tcr-2026-0728","DOIUrl":"https://doi.org/10.21037/tcr-2026-0728","url":null,"abstract":"<p><strong>Background: </strong>Studies have identified a correlation between fine particulate matter (PM2.5) exposure and the progression of hepatocellular carcinoma (HCC), though the underlying mechanisms remain unclear. This study investigates the regulatory effects of PM2.5 on HCC migration.</p><p><strong>Methods: </strong>Wound healing assays were conducted to evaluate the invasion and migration capabilities of liver cancer cells. Western blot and immunohistochemistry were employed to assess E-cadherin and Vimentin expression levels. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to measure miR-25 expression in both MHCC97H cells and liver cancer cells of mice. miR-25 mimics and inhibitors were transfected into MHCC97H cells to explore the role of miR-25 in PM2.5-induced progression of liver cancer cells.</p><p><strong>Results: </strong>PM2.5 exposure suppressed E-cadherin expression while upregulating Vimentin, thereby enhancing MHCC97H cell migration. PM2.5 also elevated miR-25 expression in MHCC97H cells. Transfection with miR-25 mimics further augmented PM2.5-induced migration, whereas transfection with miR-25 inhibitors attenuated these effects. This suggests that miR-25 serves as a key mediator in PM2.5-induced promotion of liver cancer invasion and migration. Animal experiments demonstrated that PM2.5 exposure facilitated tumor growth, invasion, and migration in liver cancer models, accompanied by elevated miR-25 expression levels.</p><p><strong>Conclusions: </strong>This study confirms that PM2.5 promotes HCC cell migration by targeting miR-25, and significantly promotes tumor growth and epithelial-mesenchymal transition (EMT) phenotypic alterations <i>in vivo</i>, indicating that PM2.5 exposure drives HCC malignant progression through miR-25 dysregulation. Importantly, it also provides the first direct functional link among PM2.5 exposure, miR-25 dysregulation, and HCC progression, and identify miR-25 as a potential therapeutic target and prognostic biomarker for HCC.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 9","pages":"700"},"PeriodicalIF":2.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Incidence, characteristics, and exploratory analysis of factors associated with pelvic osteitis/osteoradionecrosis after radiotherapy for cervical cancer: a single-center retrospective cohort study with an unmatched case-control analysis. 宫颈癌放疗后盆腔骨炎/骨放射性坏死相关因素的发生率、特征和探索性分析:一项单中心回顾性队列研究,无与伦比的病例对照分析。
IF 2.1 4区 医学
Translational cancer research Pub Date : 2026-09-30 Epub Date: 2026-09-18 DOI: 10.21037/tcr-2026-2270
Sijia Deng, Jie Li, Zexin Wang, Renming Lv, En Long, Yuanyuan Luo, Zihan Chen, Tingting Dai, Rui Huang, Song Qiu, Ruisi Wang, Huijie Wei, Dan Zhou, Yuxi Dong, Shuqiang Zhang, Fengmei Wen, Ruyan Liu
{"title":"Incidence, characteristics, and exploratory analysis of factors associated with pelvic osteitis/osteoradionecrosis after radiotherapy for cervical cancer: a single-center retrospective cohort study with an unmatched case-control analysis.","authors":"Sijia Deng, Jie Li, Zexin Wang, Renming Lv, En Long, Yuanyuan Luo, Zihan Chen, Tingting Dai, Rui Huang, Song Qiu, Ruisi Wang, Huijie Wei, Dan Zhou, Yuxi Dong, Shuqiang Zhang, Fengmei Wen, Ruyan Liu","doi":"10.21037/tcr-2026-2270","DOIUrl":"https://doi.org/10.21037/tcr-2026-2270","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Pelvic radiotherapy is the standard treatment for locally advanced cervical cancer and has substantially improved patient survival. As survival has increased, late radiation-related complications have become increasingly important. Radiation osteitis (RO) and osteoradionecrosis (ORN) are uncommon but potentially disabling forms of radiation-induced pelvic bone injury. However, most previous studies have focused on pelvic insufficiency fractures (PIFs) rather than pelvic RO/ORN. Consequently, the incidence, clinical characteristics, imaging features, and risk factors of pelvic RO/ORN remain poorly defined, particularly in patients treated with contemporary intensity-modulated radiotherapy (IMRT). This study aimed to investigate the incidence, clinical and imaging characteristics, and potential risk factors of pelvic RO/ORN in cervical cancer patients receiving pelvic radiotherapy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A retrospective cohort study with an unmatched case-control analysis was conducted among 308 cervical cancer patients treated with pelvic radiotherapy between January 2015 and December 2021. After follow-up and imaging review, 28 patients diagnosed with pelvic RO/ORN were identified. Fifty-six controls were selected by simple random sampling without replacement from the remaining cohort members in whom RO/ORN was not identified during available follow-up. Clinical characteristics, tumor features, and treatment-related variables were compared between groups. Univariable and multivariable logistic regression analyses were exploratory.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Pelvic RO/ORN was identified in 28 of 308 patients, corresponding to an incidence of 9.1%. The median time to diagnosis was 22.5 months [interquartile range (IQR), 15.5-33.0 months] after radiotherapy. The sacrum/sacroiliac region and ilium were the most frequently involved sites. Typical imaging findings included mixed osteolytic and sclerotic lesions, irregular cortical disruption, and inflammatory changes in adjacent soft tissues. Seventeen patients (60.7%) had pelvic or hip pain or movement-related symptoms, whereas 11 (39.3%) were identified on surveillance imaging without apparent symptoms. No statistically significant between-group differences were observed for the clinical and treatment variables examined (all P&gt;0.05). Exploratory multivariable logistic regression did not identify clear independent associations in this dataset.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Pelvic RO/ORN is a clinically relevant late effect of pelvic radiotherapy for cervical cancer. In this dataset, no clear predictors were identified among the clinical and treatment variables examined; this negative finding should be interpreted cautiously because the number of events was limited and patient-specific pelvic bone dosimetry and bone-health measures were unavailable. Future risk assessment should move beyond conventional clinical parameters by integrating dosimetric, i","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 9","pages":"712"},"PeriodicalIF":2.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Personalized prediction of sequential therapeutic responses in HR+/HER2-low breast cancer using patient-derived organoids. 使用患者来源的类器官对低HR+/ her2乳腺癌的序贯治疗反应进行个性化预测
IF 2.1 4区 医学
Translational cancer research Pub Date : 2026-09-30 Epub Date: 2026-08-26 DOI: 10.21037/tcr-2026-0950
Wei Zhao, Zhongni Wu, Chengpan Li, Hongbo Zhang, Dabing Huang, Lijuan Wang, Xiaodan Zhang, Juanjuan Zhang, Xinyu Ma, Yifan Wen, Joseph Benjamin Holman, Xudong Yuan, Tingting Wang, Wei Wang, Weiping Ding, Yueyin Pan
{"title":"Personalized prediction of sequential therapeutic responses in HR+/HER2-low breast cancer using patient-derived organoids.","authors":"Wei Zhao, Zhongni Wu, Chengpan Li, Hongbo Zhang, Dabing Huang, Lijuan Wang, Xiaodan Zhang, Juanjuan Zhang, Xinyu Ma, Yifan Wen, Joseph Benjamin Holman, Xudong Yuan, Tingting Wang, Wei Wang, Weiping Ding, Yueyin Pan","doi":"10.21037/tcr-2026-0950","DOIUrl":"https://doi.org/10.21037/tcr-2026-0950","url":null,"abstract":"<p><strong>Background: </strong>The clinically recommended treatment for hormone receptor-positive/human epidermal growth factor receptor 2-low (HR+/HER2-low) advanced breast cancer involves endocrine therapy (e.g., fulvestrant) followed by antibody-drug conjugates (ADCs) such as trastuzumab deruxtecan (T-DXd; formerly DS-8201) and sacituzumab govitecan (SG). However, the therapeutic outcomes of this sequential regimen remain suboptimal, and direct evidence is lacking as to whether this sequence is optimal. Additionally, the sequence of DS-8201 and SG is also unknown. Patient-derived organoids (PDOs) have emerged as a promising preclinical tool, shown to predict personalized drug responses and correlate well with clinical outcomes. Therefore, using PDOs from HR+/HER2-low breast cancer, this study aims to systematically evaluate the antitumor effects of different administration sequences involving fulvestrant and ADCs (i.e., DS-8201 or SG), as well as DS-8201 and SG and to provide evidence for optimizing treatment sequencing.</p><p><strong>Methods: </strong>PDOs were established from fresh breast cancer tissues and characterized by immunohistochemistry (IHC), hematoxylin and eosin (H&E) staining, and immunofluorescence (IF) to confirm histopathological and phenotypic features fidelity to original tumors. Organoid viability was assessed using the CellTiter-Glo 3D (CTG-3D) assay, and morphological changes were monitored by bright-field microscopy. After treatment with fulvestrant, DS-8201, or SG alone, IHC and IF were performed to detect key proteins involved in the mechanism of action of SG and DS-8201.</p><p><strong>Results: </strong>Our results demonstrated that administering DS-8201 or SG followed by fulvestrant yielded superior antitumor effects compared with the reverse sequence (fulvestrant followed by ADCs). Moreover, organoids revealed marked patient heterogeneity in response to the sequential administration of DS-8201 and SG (i.e., DS-8201 then SG <i>vs.</i> SG then DS-8201). Notably, relying solely on expression levels of biomarkers alone was insufficient to accurately predict ADCs sensitivity in organoids that had received prior therapy.</p><p><strong>Conclusions: </strong>The sequence of DS-8201/SG followed by fulvestrant is a more suitable treatment regimen than the conventional sequence (fulvestrant followed by ADCs) for HR+/HER2-low breast cancer. This study provides important preclinical evidence supporting the optimization of therapy sequences in personalized medicine and advances the application of organoid-based models in oncology research.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 9","pages":"689"},"PeriodicalIF":2.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Assessing the utility of ctDNA as a prognostic marker in advanced ER-positive/HER2-negative breast cancer. 评估ctDNA作为晚期er阳性/ her2阴性乳腺癌预后标志物的效用。
IF 2.1 4区 医学
Translational cancer research Pub Date : 2026-08-31 Epub Date: 2026-08-24 DOI: 10.21037/tcr-2026-0929
Moumita Chaki, Christopher Morrow, Hanna Ahlgren
{"title":"Assessing the utility of ctDNA as a prognostic marker in advanced ER-positive/HER2-negative breast cancer.","authors":"Moumita Chaki, Christopher Morrow, Hanna Ahlgren","doi":"10.21037/tcr-2026-0929","DOIUrl":"10.21037/tcr-2026-0929","url":null,"abstract":"","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 8","pages":"671"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148931004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dietary risk factors for lung cancer: an umbrella review of systematic review and meta-analysis. 肺癌的饮食危险因素:系统评价和荟萃分析的综合综述。
IF 2.1 4区 医学
Translational cancer research Pub Date : 2026-08-31 Epub Date: 2026-07-30 DOI: 10.21037/tcr-2026-1439
Zirong Wen, Zhimou Zhang, Chenyang Wu, Dawei Cao
{"title":"Dietary risk factors for lung cancer: an umbrella review of systematic review and meta-analysis.","authors":"Zirong Wen, Zhimou Zhang, Chenyang Wu, Dawei Cao","doi":"10.21037/tcr-2026-1439","DOIUrl":"10.21037/tcr-2026-1439","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer poses a substantial global public health burden, and dietary factors represent potentially modifiable targets for primary prevention. This study evaluates the methodological quality, risk of bias, and reliability of evidence related to dietary risk factors for lung cancer through an umbrella review and provides a comprehensive overview of the identified risk factors.</p><p><strong>Methods: </strong>This review protocol has been registered on PROSPERO. A systematic search was conducted in PubMed, Embase, Web of Science, and Cochrane Database of Systematic Reviews to collect meta-analyses on dietary factors and lung cancer risk published up to March 2026. The methodological quality of the included studies was evaluated using the A Measurement Tool to Assess Systematic Reviews (AMSTAR) tool, and the evidence strength of each outcome was rated based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.</p><p><strong>Results: </strong>There were 57 meta-analyses included, covering 57 diet-related factors. The association between folate and reduced risk of lung cancer is supported by moderate-quality evidence, while most other factors (such as beta-carotene, red and processed meat, etc.) have low or very low quality evidence. A healthy dietary pattern is associated with a lower risk of lung cancer risk, while a Western/meat diet pattern and a high glycemic load diet are positively associated with risk.</p><p><strong>Conclusions: </strong>The quality of evidence for the association between most dietary factors and lung cancer risk is low, with only folate showing moderate-quality evidence, indicating that current research is not sufficient to support strong causal inference. In the future, it is necessary to conduct well-designed prospective cohort studies and randomized controlled trials to provide a higher-quality scientific basis for precise nutritional prevention of lung cancer.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 8","pages":"655"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559595/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148931069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Constructing an in vitro choriocarcinoma model by three-dimensional bioprinting. 三维生物打印技术构建体外绒毛膜癌模型。
IF 2.1 4区 医学
Translational cancer research Pub Date : 2026-08-31 Epub Date: 2026-07-21 DOI: 10.21037/tcr-2026-1102
Ying-Chao Hu, Ming-Hao Sun, Hua Li, Chang-Can Li
{"title":"Constructing an <i>in vitro</i> choriocarcinoma model by three-dimensional bioprinting.","authors":"Ying-Chao Hu, Ming-Hao Sun, Hua Li, Chang-Can Li","doi":"10.21037/tcr-2026-1102","DOIUrl":"10.21037/tcr-2026-1102","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Choriocarcinoma is a rare and highly aggressive trophoblastic tumor. Although in-depth research has been conducted on the treatment options for choriocarcinoma, especially chemotherapy regimens, there are still 10% to 20% of choriocarcinoma patients who develop resistance or experience tumor recurrence. The research on the pathogenesis of choriocarcinoma and its treatment remains a major challenge and an unresolved clinical issue. Accurately replicating the key characteristics of choriocarcinoma in preclinical tumor models is crucial for research into tumor mechanisms and treatment. Up to now, the lack of a universal &lt;i&gt;in vitro&lt;/i&gt; model required for studying tumor-related diseases is a key problem faced by researchers. It is notable that three-dimensional bioprinting (3DP) technology has seen expanding utilization across multiple domains of biomedical research. To this end, we aimed to employ 3DP technology to construct an &lt;i&gt;in vitro&lt;/i&gt; choriocarcinoma model and to comprehensively compare it with conventional two-dimensional (2D) culture systems in multiple aspects.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A 3DP approach was employed to generate an &lt;i&gt;in vitro&lt;/i&gt; choriocarcinoma model, and the cells in this model were comprehensively compared with those in traditional 2D cultured cells. A fluorescence live/dead kit was used to assess cell viability. Proliferation of JEG-3 cells was assessed by the Cell Counting Kit-8 (CCK-8) assay. We also analyzed the gene expression of 2D and 3D bioprinted cells. Finally, we used antitumor drugs to conduct drug response tests on the cells in the 2D and 3DP groups.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The cells in the 3DP system exhibited stronger vitality, metabolic activity, and key tumor biological characteristics, compared to the cells cultured in a single layer in the 2D cultures. Throughout the entire observation window, JEG-3 cells in the 3D bioprinted model proliferated more robustly, suggesting that the 3D bioprinted environment supports sustained cell growth and is suitable for long-term experiments. Cells in the 3D bioprinted model exhibited significantly higher levels of genes associated with proliferation, metastasis, drug resistanace, immune suppression, and epithelial-to-mesenchymal transition (EMT), compared to those cultured in 2D. We also found that the 3D bioprinted model released markedly greater amounts of human chorionic gonadotropin (hCG) than the 2D culture. The results of drug screening assays indicated that the half-maximal inhibitory concentration (IC&lt;sub&gt;50&lt;/sub&gt;) values for three tested chemotherapeutic agents were substantially elevated in the 3D bioprinted model relative to the 2D model.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This study demonstrates the feasibility of engineering a 3D bioprinted tumor model using a composite hydrogel system to mimic the &lt;i&gt;in vivo&lt;/i&gt; tumor microenvironment more effectively. The 3D bioprinted microtissue model provides a realist","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 8","pages":"612"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148930872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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