Translational Oncology最新文献

{"title":"A clinical study on the efficacy of concurrent chemoradiotherapy combined with targeted therapy and hyperthermia in patients with locally advanced cervical cancer","authors":"Yuhan Jia ,&nbsp;Feng Zhang ,&nbsp;Kun Zou ,&nbsp;Lijuan Zou","doi":"10.1016/j.tranon.2025.102516","DOIUrl":"10.1016/j.tranon.2025.102516","url":null,"abstract":"<div><h3>Objective</h3><div>To explore novel therapeutic approaches for locally advanced cervical cancer (LACC), we evaluated the efficacy and safety of hyperthermia (HT) and/or targeted therapy combined with cisplatin-based concurrent chemoradiotherapy (CCRT).</div></div><div><h3>Methods</h3><div>This retrospective study analyzed 119 LACC patients (tumor diameter ≥4 cm) treated at our institution (Jan 2021–Oct 2024), stratified into: CCRT (<em>n</em> = 48), targeted therapy + CCRT (T-CCRT, <em>n</em> = 44), and HT + targeted therapy + CCRT (HT-T-CCRT, <em>n</em> = 27). Complete/objective response rates (CRR/ORR) at 3/12 months were assessed. Statistical analyses were performed using standard software to compare efficacies and evaluate adverse events (AEs).</div></div><div><h3>Results</h3><div>1. Efficacy: At 3 months, HT-T-CCRT achieved the highest CRR (85.19 % vs. CCRT 58.33 %, <em>P</em> &lt; 0.05) and ORR (96.30 %). T-CCRT showed significantly higher ORR (95.46 % vs. CCRT 81.25 %, <em>P</em> &lt; 0.05). At 12 months, no significant intergroup differences existed in CRR (58.33 %/61.36 %/77.78 %) or ORR (70.83 %/75.00 %/77.78 %). 2. Safety: CCRT had lower diarrhea (52.08 % vs. 81.82 %) and vomiting (50.00 % vs. 86.36 %) rates than T-CCRT (both <em>P</em> &lt; 0.05). HT-T-CCRT further reduced vomiting (55.56 % vs. 86.36 %), diarrhea (55.56 % vs. 81.82 %), and liver impairment (22.22 % vs. 47.73 %) versus T-CCRT (all <em>P</em> &lt; 0.05), with comparable safety to CCRT.</div></div><div><h3>Conclusions</h3><div>Efficacy: The targeted combination group had higher ORR and CRR at 3/12 months than chemoradiation, with a significant 3-month ORR difference. The thermotherapy-targeted group showed the highest CRR/ORR, with significantly better 3-month CRR vs chemoradiation but not vs targeted alone. Safety: Diarrhea/vomiting were lower with chemoradiation than targeted; thermotherapy-targeted had lower diarrhea/vomiting/liver injury than targeted alone, with comparable overall AEs to chemoradiation.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"61 ","pages":"Article 102516"},"PeriodicalIF":5.0,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144932961","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":"Lipid metabolism of clear cell renal cell carcinoma predicts survival and affects intratumoral CD8 T cells","authors":"Jakob Simeth ,&nbsp;Simon Engelmann ,&nbsp;Roman Mayr ,&nbsp;Sebastian Kaelble ,&nbsp;Florian Weber ,&nbsp;Renate Pichler ,&nbsp;Katja Dettmer ,&nbsp;Peter J Oefner ,&nbsp;Marcus Höring ,&nbsp;Luisa Symeou ,&nbsp;Katharina Freitag ,&nbsp;Kilian Wagner ,&nbsp;Maximilian Burger ,&nbsp;Wolfgang Herr ,&nbsp;Marina Kreutz ,&nbsp;Rainer Spang ,&nbsp;Gerhard Liebisch ,&nbsp;Peter J Siska","doi":"10.1016/j.tranon.2025.102513","DOIUrl":"10.1016/j.tranon.2025.102513","url":null,"abstract":"<div><h3>Background</h3><div>Clear cell renal cell carcinoma (ccRCC), the most common RCC subtype, both accumulates and depletes selected lipid species. However, the prognostic role of lipid metabolic reprogramming in ccRCC has not been studied in detail so far. In addition, ccRCC can show a dense immune infiltration. Intriguingly, tumor infiltration with T cells can be negatively prognostic in RCC. This comprehensive study of the transcriptome, lipidome and immune infiltrate of ccRCC tumors elucidates the prognostic role of lipid-metabolic pathways and their possible interaction with tumor infiltrating T cells.</div></div><div><h3>Methods</h3><div>Freshly resected RCC tumors and adjacent kidney tissues and extracellular fluids were processed and subjected to mass-spectrometry based lipidomics and lipid staining (<em>n</em> = 36). Hierarchical clustering was performed using the transcriptome data and gene group definitions obtained from publicly available databases (TCGA, 526 ccRCC and 287 papillary RCC). Phenotype, activation, proliferation and fatty acid uptake were assessed in ccRCC infiltrating T cells at single cell level ex vivo (<em>n</em> = 22) or after treatment with oleate and palmitate in vitro (<em>n</em> = 4).</div></div><div><h3>Results</h3><div>ccRCC tumors accumulated lipids, notably those containing oleate. Clustering of RCC patients based on the expression of genes involved in fatty acid degradation (FAD) and cholesterol synthesis (chol) was able to predict survival and was superior to clustering based on genes involved in fatty acid synthesis or fatty acid elongation. Further, prognostic clustering was observed in ccRCC, but not in papillary RCC tumors, and it was independent of major clinical parameters. The FAD/chol cluster with poor prognosis showed a trend toward decreased prevalence of <em>VHL</em> mutations and higher <em>c-MET</em> copy numbers. Moreover, this cluster associated with dysregulated inflammation hallmarked by low <em>PRF1</em>, but high <em>IFNɣ</em> expression. Tumor infiltrating T cells showed increased fatty acid uptake, and CD8 T cell infiltration negatively correlated with oleate-associated lipid species found in the extracellular space of ccRCC tumors. Lastly, oleate treatment ex vivo suppressed the activation and perforin production of CD8 T cells from ccRCC tumors.</div></div><div><h3>Conclusions</h3><div>Our study describes a robust, prognostic clustering of lipid gene expression that is both ccRCC-specific and independent of major parameters such as tumor size or aggressiveness. Furthermore, we propose that oleate accumulation in the RCC lipidome affects intratumoral CD8 T cell infiltration and function.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"61 ","pages":"Article 102513"},"PeriodicalIF":5.0,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144932960","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":"SP1-Mediated upregulation of CLEC18B promotes the proliferation and metastasis of glioma through regulation of the Wnt/β-Catenin/EMT Pathway","authors":"Hongliang Liu ,&nbsp;Bin Zhu ,&nbsp;Yong Cui ,&nbsp;Wei Liu ,&nbsp;Qiang Xu ,&nbsp;Xiangrui Lu ,&nbsp;Zhaowen Tan ,&nbsp;Yu Tian ,&nbsp;Wei Xu","doi":"10.1016/j.tranon.2025.102515","DOIUrl":"10.1016/j.tranon.2025.102515","url":null,"abstract":"<div><div>Glioma is one of the most aggressive and lethal brain tumors, with poor prognosis and limited treatment options. This study examined the function of CLEC18B in glioma development and its viability as a predictive biomarker. Pan-cancer research demonstrated that CLEC18B is dysregulated in several tumor types, with elevated expression associated with reduced overall survival (OS) and disease-specific survival (DSS) in patients with different malignancies, including glioma. CLEC18B was markedly increased in glioblastoma (GBM) and lower-grade glioma (LGG) tissues relative to normal tissues, and its elevated expression correlated with worse survival outcomes in both LGG and GBM patients. CLEC18B expression was an independent predictive indicator for OS and DSS in GBM, with expression levels being affected by DNA methylation status. We investigated the regulatory mechanisms governing CLEC18B expression and found SP1 as a major transcription factor that directly modulates CLEC18B. Our findings validated that SP1 associates with the CLEC18B promoter, and the silencing of SP1 resulted in a substantial decrease in CLEC18B expression. The suppression of CLEC18B functionally decreased glioma cell proliferation, motility, and invasion in vitro, and lowered tumor development in vivo. Furthermore, CLEC18B knockdown modified the Wnt/β-catenin/EMT signaling pathway by decreasing mesenchymal markers and increasing epithelial markers. Administration of a Wnt/β-catenin agonist partially mitigated the consequences of CLEC18B knockdown, indicating that CLEC18B facilitates glioma growth via the stimulation of this pathway. In conclusion, CLEC18B is crucial to glioma development, serving as a principal regulator of cell proliferation, migration, and invasion via the Wnt/β-catenin/EMT pathway. CLEC18B may function as a prospective prognostic biomarker and therapeutic target for glioma therapy.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"61 ","pages":"Article 102515"},"PeriodicalIF":5.0,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144912770","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":"The tumor suppressor DACT3 sensitizes triple-negative breast cancer to apatinib by inhibiting the Wnt/β-catenin pathway","authors":"Jing Wu ,&nbsp;Rui Tian ,&nbsp;Mei Liu ,&nbsp;Yijing Liu ,&nbsp;Bianfei Shao ,&nbsp;Xiaohua Zeng","doi":"10.1016/j.tranon.2025.102509","DOIUrl":"10.1016/j.tranon.2025.102509","url":null,"abstract":"<div><div>Apatinib, a small-molecule inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2), shows efficient antitumor activity in heavily pretreated metastatic triple-negative breast cancer (TNBC). However, not all patients respond to apatinib, indicating that it is necessary to identify response biomarkers for more precise treatment and investigate the underlying mechanisms of apatinib resistance to develop new treatment strategies for TNBC. In this study, we identified the disheveled binding antagonist of beta-catenin 3 (DACT3) as a biomarker for apatinib sensitivity, as its expression level is significantly higher in apatinib-sensitive patients and positively correlates with longer survival. Furthermore, we explored that the exogenous expression of DACT3 could downregulate the IC₅₀ of apatinib (Vector vs DACT3: 16.04 μM vs 8.81 μM in MDA-MB231 cells, 19.65 μM vs 9.42 μM in YCCB1 cells) by inhibiting the Wnt/β-catenin signaling, a pro-malignancy pathway that leads to apatinib resistance through crosstalk with the VEGF/VEGFR2 pathway. In summary, our results indicate that DACT3 is a potential biomarker for predicting the response to apatinib and a new therapeutic target for improving TNBC sensitivity to apatinib.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"61 ","pages":"Article 102509"},"PeriodicalIF":5.0,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144912769","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":"An anti-CEA affibody showing high-definition staining in human pancreatic cancer tissue sections and selective tumor targeting in vivo","authors":"Johan Nilvebrant ,&nbsp;Carlos Fernández Moro ,&nbsp;Eleftherios Papalanis ,&nbsp;Masih Ostad Novin ,&nbsp;Haozhong Ding ,&nbsp;Ruonan Li ,&nbsp;Maryam Oroujeni ,&nbsp;Arun Selvam ,&nbsp;Béla Bozóky ,&nbsp;Torbjörn Gräslund ,&nbsp;Timea Szekerczes ,&nbsp;Tatiana Sandalova ,&nbsp;Hugh Salter ,&nbsp;Adnane Achour ,&nbsp;Vladimir Tolmachev ,&nbsp;Mikael Björnstedt ,&nbsp;Per-Åke Nygren","doi":"10.1016/j.tranon.2025.102512","DOIUrl":"10.1016/j.tranon.2025.102512","url":null,"abstract":"<div><div>We report development and characterization of small non-immunoglobulin affibody affinity proteins directed to the highly glycosylated human carcinoembryonic antigen-related adhesion molecule 5 (CEACAM5, CEA), and their use in immunohistochemical (IHC) analyses of human pancreatic cancer samples and for <em>in vivo</em> tumor imaging. A total of nineteen unique anti-CEA affibodies were identified from large phage display libraries constructed using combinatorial protein engineering of a small 58 amino acid three-helix bundle protein domain. Molecular modeling suggested that all enriched clones share a binding surface with several clustered tryptophan residues interacting with a hydrophobic patch in the N1 domain of CEA centered around a phenylalanine residue. One variant, designated as C9, exhibited the highest affinity in biosensor analyses and was reformatted into a 15 kDa homodimer expressed in <em>Escherichia coli</em>. The biotinylated form, C9-C9-Bio, was evaluated for its IHC performance on matched frozen and formalin-fixed, paraffin-embedded (FFPE) sections of human pancreatic cancer samples (<em>n</em> = 7). Compared to clinical-grade monoclonal antibodies II-7 and CEA31, as well as a polyclonal reagent, C9-C9-Bio demonstrated highly sensitive CEA detection with minimal background staining. Statistical analyses including intraclass correlation and Bland-Altman assessments revealed excellent agreement between C9-C9-Bio and the two monoclonal antibodies in FFPE tissue samples. Further, a ^99mTc[Tc]-labeled C9-C9 construct showed CEA-dependent binding to human cancer cell lines <em>in vitro</em>, and selectively bound to CEA-expressing BxPC3 xenografts in mice when investigated as a tracer for <em>in vivo</em> imaging, allowing for a visualization of tumors after four hours. In summary, these findings highlight the potential use of the easily produced CEA-binding C9 affibody for various clinical applications, including IHC and medical imaging, and as a targeting moiety for directing various therapeutic modalities to CEA-expressing tumors.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"61 ","pages":"Article 102512"},"PeriodicalIF":5.0,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144907369","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":"Lnc-THAP7-AS1 suppresses the ovarian cancer progression by targeting miR-92b-5p/fatty acid 2-hydroxylase signal axis","authors":"Meili Pei ,&nbsp;Yanqi Yang ,&nbsp;Bing Su ,&nbsp;Na Li ,&nbsp;Minyi Zhao ,&nbsp;Juan Zhao ,&nbsp;Ting Yang ,&nbsp;Li Wang ,&nbsp;Shimin Quan ,&nbsp;Ruifang Sun ,&nbsp;Xiaofeng Yang","doi":"10.1016/j.tranon.2025.102514","DOIUrl":"10.1016/j.tranon.2025.102514","url":null,"abstract":"<div><h3>Background</h3><div>Ovarian cancer (OC) ranks among the most lethal gynecological malignancies. Research has highlighted long noncoding RNAs (lncRNAs) as promising novel molecular targets for cancer therapy. This study endeavors to identify novel lncRNAs, elucidate their specific roles, and unravel their regulatory mechanism in OC development.</div></div><div><h3>Methods</h3><div>Utilizing LncRNA Microarray technology, we screened for differentially expressed RNAs, ultimately selecting THAP7-AS1 for in-depth investigation. RNA pull-down, luciferase assays and FISH were performed to validate the interaction among THAP7-AS1, miR-92b-5p and FA2H. qRT-PCR was conducted to assess the expression of THAP7-AS1, miR-92b-5p and FA2H in OC tissues and cell lines. Cellular biological effects were examined using proliferation CCK-8 and EdU assays, chamber Transwell migration assays, and flow cytometer for apoptosis analysis. Additionally, nude mice xenograft models were established to evaluate the in vivo effect of THAP7-AS1 on tumor growth.</div></div><div><h3>Results</h3><div>Our findings revealed a downregulation of THAP7-AS1 in OC tissues and cells. Overexpression of THAP7-AS1 inhibited cell proliferation, migration, and induced apoptosis. miR-92b-5p was identified as a sponge target of THAP7-AS1, with its expression upregulated in OC tissues and cells. Forced expression of miR-92b-5p exhibited cellular effects opposite to those of THAP7-AS1 overexpression. Additionally, FA2H was confirmed as a direct target of miR-92b-5p Silencing FA2H suppressed apoptosis, promoted proliferation and migration. In vivo experiments showed overexpression of THAP7-AS1 significantly reduced tumor volume and weight.</div></div><div><h3>Conclusion</h3><div>THAP7-AS1 is firstly reported as a tumor suppressor in OC by targeting the miR-92b-5p/FA2H axis. Our findings suggest that THAP7-AS1 holds potential as therapeutic target in OC treatment.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"61 ","pages":"Article 102514"},"PeriodicalIF":5.0,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144907368","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":"Histone Deacetylase Inhibitors orchestrate epigenetic signalling and alter the nucleoporins and nuclear envelope in cervical cancer","authors":"Harsha Rani ,&nbsp;Shabir Ahmad Ganai ,&nbsp;Vijayalakshmi Mahadevan","doi":"10.1016/j.tranon.2025.102510","DOIUrl":"10.1016/j.tranon.2025.102510","url":null,"abstract":"<div><div>Histone Deacetylases inhibitors (HDACi) modulate the acetylation profile of lysines on the histone tails to facilitate DNA accessibility to transcription factors. While the phenotypes caused by HDAC inhibition on cancer cells have been studied extensively, the nuclear geometry and expression signatures modulated by these enzymes have not been well understood.This work attempts to understand the functional implication of HDAC inhibitor treatment (NaB and MS275) on cervical cancer cells. We observed an increase in nuclear area upon HDAC inhibition correlating with an increase in expression of active histone marks and lamins and a decrease in levels of repressive epigenetic marks. Our transcriptomic sequencing of HeLa cells treated individually with these inhibitors have identified dysregulation of nucleoporins affecting the nucleocytoplasmic exchange and nucleo-cytoplasmic transport through the nuclear pores. These act in concert with the increase in acetylation due to HDAC inhibition and contribute to the increase in nuclear area. In order to derive clinical implications of the observed mechano signalling genes and epigenetic factors differentially expressed in HeLa cells, we verified these on a TCGA cervical cancer cohort of 148 patients and observed an upregulation of various nucleoporins in cervical cancer patients. Interestingly, the low expression of LMNA and high expression of NUP58 were associated with lower survival rate in the cohort. These signatures have also been validated on Indian cervical cancer tissues. This novel and intricate mechanism of modulating epigenetic regulation and nuclear architecture changes by HDAC inhibition can be utilized for designing targetted epigenetic therapy for cervical cancer.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"61 ","pages":"Article 102510"},"PeriodicalIF":5.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144902336","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":"Luteolin suppresses cell migration and invasion via targeting miR-6809-5p/FLOT1/FAK and eliciting EMT in hepatocellular carcinoma","authors":"Pei-Wei Yang ,&nbsp;Su-Ping Ma ,&nbsp;Xin-Ju Chen ,&nbsp;Fang-Ming Yang ,&nbsp;Shou-Mei Wang ,&nbsp;Qian Wang ,&nbsp;Shu-Hui Zhang","doi":"10.1016/j.tranon.2025.102511","DOIUrl":"10.1016/j.tranon.2025.102511","url":null,"abstract":"<div><div>Luteolin, 3′,4′,5,7-tetrahydroxyflavone, a natural flavonoid component found in various Chinese herbs such as Scutellaria barbata D. Don, honeysuckle, chrysanthemum, schizonepeta, and ajuga decumbens, exhibits potential for cancer prevention and therapy. This study elucidates the molecular mechanisms by which luteolin, an active constituent of Scutellaria barbata, inhibits invasion and metastasis of hepatocellular carcinoma (HCC) cell lines both in vitro and in vivo. The oncogenic microRNA miR-6809–5p was found to be aberrantly upregulated in HCC tissues and downregulated by luteolin in HCC cells; overexpression of miR-6809–5p was able to restore the anti-HCC effects of luteolin via the miR-6809–5p/FLOT1/FAK signaling pathway. Furthermore, luteolin suppressed HCC invasion, metastasis, and epithelial-mesenchymal transition (EMT) through modulation of the PI3K/AKT/mTOR pathway, affecting markers such as E-cadherin, β-catenin, Vimentin, N-cadherin, Snail, Twist, and Slug. This research demonstrates that luteolin effectively inhibits HCC cell migration and invasion and significantly suppresses epithelial mesenchymal transition (EMT) both in vitro and in vivo.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"61 ","pages":"Article 102511"},"PeriodicalIF":5.0,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144902337","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":"Corrigendum to “Construction of a novel cancer‑associated fibroblast‑related signature to predict clinical outcome and immune response in cervical cancer” [Transl Oncol. 2024;46:102001]","authors":"Zhongxuan Gui ,&nbsp;Yingquan Ye ,&nbsp;Yu Li ,&nbsp;Zhengting Ren ,&nbsp;Nan Wei ,&nbsp;Li Liu ,&nbsp;Hua Wang ,&nbsp;Mei Zhang","doi":"10.1016/j.tranon.2025.102499","DOIUrl":"10.1016/j.tranon.2025.102499","url":null,"abstract":"","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"61 ","pages":"Article 102499"},"PeriodicalIF":5.0,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145105600","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":"Elucidating divergent biology in uterine carcinosarcoma","authors":"Vikas Garg ,&nbsp;Stephenie D. Prokopec ,&nbsp;Simone C. Stone ,&nbsp;Sara Pakbaz ,&nbsp;Min Li Chen ,&nbsp;Bernard Lam ,&nbsp;Czin Czin Benito ,&nbsp;Michelle Mcmullen ,&nbsp;Ilinca Lungu ,&nbsp;Samanta Del Rossi ,&nbsp;Anthony Msan ,&nbsp;Valerie Bowering ,&nbsp;Valentin Sotov ,&nbsp;Christine Tran ,&nbsp;Marcus O. Butler ,&nbsp;Amit M. Oza ,&nbsp;Phedias Diamandis ,&nbsp;Ben X. Wang ,&nbsp;Stephanie Lheureux","doi":"10.1016/j.tranon.2025.102506","DOIUrl":"10.1016/j.tranon.2025.102506","url":null,"abstract":"<div><h3>Objectives</h3><div>Uterine carcinosarcoma (UCS) is an aggressive malignancy characterized by epithelial (C) and mesenchymal (S) components, with complex biology and poor treatment response. This study aims to enhance understanding of UCS through genomic, epigenomic, and transcriptomic analysis.</div></div><div><h3>Methods</h3><div>Microdissected (C and S) tumor samples were processed for whole-genome sequencing (WGS), RNA-seqencing, and enzymatic methylation sequencing (EM-Seq). Multiplex immunohistochemistry (mIHC) and computational pathology techniques were employed to assess tumour microenvironment (TME)<em>.</em></div></div><div><h3>Results</h3><div>WGS and EM-seq of 18 samples from 9 patients revealed a low tumor mutation burden (TMB; median = 0.97 mutations/Mb) and no evidence of microsatellite instability (MSI). Driver mutations were identified in TP53 (94 %), PIK3CA (33 %), and PPP2R1A (22 %). Copy-number (CN) analysis revealed recurrent amplifications of MYC (67 %), PIK3CA (61 %), CCNE1 (56 %), AKT2 (44 %), and SMARCA4 (39 %). Comparative analysis of the C and S regions revealed no significant differences in mutation frequency, CN, transcriptomic and methylomic profiles. Both regions exhibited global hypomethylation, with functional enrichment for xenobiotic metabolism pathways in C and epithelial-to-mesenchymal transition pathways in S regions. Comparitive mIHC performed on 21 cases showed similar T cell and B cell densities, but a higher density of tumour-associated macrophages and PD-L1+ cells in the S component. Computational morphologic analysis showed substantial histomorphologic heterogeneity within and across UCS cases.</div></div><div><h3>Conclusion</h3><div>By elucidating the complex interplay between the epithelial and mesenchymal components, this study enhances our understanding of UCS and informs the development of novel therapeutic strategies targeting both genomic alterations and the TME.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"61 ","pages":"Article 102506"},"PeriodicalIF":5.0,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144890982","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}