Translational Oncology最新文献

{"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 , Xiangyu Yang , Yi Ren , Huimin Wang , Qi Zhang , Sailing Lin , Wenhao Wu , Xiaolu Yang , Jiahan Zheng , Xinzhu Liu , Xin Tao , Xiaoyong Chen , Yuxin Qian , Xiushen Li","doi":"10.1016/j.tranon.2025.102402","DOIUrl":"10.1016/j.tranon.2025.102402","url":null,"abstract":"<div><h3>Introduction</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusions</h3><div>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}

{"title":"Aberrant overexpression of m6A writer and reader genes in pediatric B-Cell Acute Lymphoblastic Leukemia (B-ALL)","authors":"Sumedha Saluja ,&nbsp;Shuvadeep Ganguly ,&nbsp;Jay Singh ,&nbsp;Ayushi Jain ,&nbsp;Gunjan Sharma ,&nbsp;Shilpi Chaudhary ,&nbsp;Karthikeyan Pethusamy ,&nbsp;Parthaprasad Chattopadhyay ,&nbsp;Anita Chopra ,&nbsp;Archna Singh ,&nbsp;Subhradip Karmakar ,&nbsp;Sameer Bakhshi ,&nbsp;Jayanth Kumar Palanichamy","doi":"10.1016/j.tranon.2025.102403","DOIUrl":"10.1016/j.tranon.2025.102403","url":null,"abstract":"<div><h3>Background</h3><div>m6A modification, regulated by writers (METTL3, METTL14), erasers (ALKBH5, FTO), and readers (IGF2BPs), is implicated in various cancers, including leukemias.</div></div><div><h3>Methods</h3><div>In our study, we examined a cohort of 227 pediatric B-ALL patients (152 primary and 75 relapsed) and assessed the expression profiles of m6A machinery genes, including both writers and erasers, as well as the IGF2BP RNA-binding proteins, which are known as m6A readers. We also quantified the absolute percentage of m6A (m6A%). The correlation between m6A machinery gene expression and patient prognosis was studied using univariate and multivariate analyses.</div></div><div><h3>Results</h3><div>Our analysis revealed a significant upregulation of m6A writers (METTL3 and METTL14), erasers (FTO), and m6A readers (IGF2BPs 1 and 3) in B-ALL patients, both in the primary and relapsed groups. m6A% levels were markedly higher in B-ALL samples than in controls. Multivariate analysis revealed that the expression of IGF2BP3, METTL3, and FTO genes, independently predicted lower overall survival and event-free survival in primary B-ALL patients.</div></div><div><h3>Conclusions</h3><div>Despite the collective dysregulation of the m6A machinery, the writers and readers appear to have a more dominant phenotype, as evidenced by the significantly elevated m6A% levels. This is the first study to analyze and establish the role of m6A machinery gene expression and its correlation with survival outcomes in a large group of B-ALL patients. These findings could aid in the development of new therapeutics targeting the m6A machinery and help predict relapse in pediatric B-ALL patients.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"56 ","pages":"Article 102403"},"PeriodicalIF":5.0,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143876527","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":"Berberine inhibits metastasis of ovarian cancer by blocking lipid metabolism, alleviating aging of adipose tissue and increasing tumor infiltrating immune cells","authors":"Xiaojie Zhang ,&nbsp;Bing Xiong ,&nbsp;Yujie Cheng ,&nbsp;Jimei Huang ,&nbsp;Jiaying Xue ,&nbsp;Xiao Li ,&nbsp;Wei Lu ,&nbsp;Jihui Zhu ,&nbsp;Lian Wang ,&nbsp;Weihong Yang ,&nbsp;Zhongping Cheng","doi":"10.1016/j.tranon.2025.102380","DOIUrl":"10.1016/j.tranon.2025.102380","url":null,"abstract":"<div><div>Extensive peritoneal metastasis and malignant ascites continue to pose substantial challenges in achieving favorable treatment outcomes for ovarian cancer. Berberine (BBR), an active component of numerous traditional Chinese herbs, has demonstrated potent anti - tumor effects across various malignancies, including ovarian cancer. In this study, we comprehensively evaluated the impact of BBR on the growth and metastasis of ovarian cancer both <em>in vitro</em> and <em>in vivo</em>. RNA - sequencing was employed to elucidate the underlying mechanisms. Specifically, we investigated lipid metabolism and mitochondrial function in ovarian cancer cells and mice, comparing BBR - treated and untreated groups. Additionally, CIBERSORT analysis and immunohistochemical (IHC) staining were utilized to confirm BBR's ability to enhance the infiltration of tumor-infiltrating immune cells into adipose tissue and improve the inflammatory tumor microenvironment. Our findings indicate that BBR significantly inhibits the growth and metastasis of ovarian cancer <em>in vitro</em> and <em>in vivo</em>. The effects can be attributed to two key processes. Firstly, BBR suppresses the lipid metabolism by downregulating lipid uptake related receptor CD36, lipid metabolic enzyme and mitochondrial function. Secondly, BBR alleviates the aging of adipose tissue and adipose derived stem cells (ADSCs), thereby decreasing the secretion of senescence-associated secretory phenotype (SASP). These ultimately lead to the increasing the improvement of tumor infiltrating immune cells, such as CD4⁺ helper T cells (CD3⁺CD4⁺) and cytotoxic T lymphocytes (CD3⁺CD8⁺), and inflammation in ovarian cancer tissue. Collectively, these findings suggested a potential therapeutic effect of BBR in the treatment of advanced ovarian cancer, particularly cases complicated by peritoneal metastasis and malignant ascites.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"56 ","pages":"Article 102380"},"PeriodicalIF":5.0,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848661","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":"TRIM25 facilitates ferroptosis in ovarian cancer through promoting PIEZO1 K63-linked ubiquitination and degradation","authors":"Ya Li,&nbsp;Fei Zhou,&nbsp;Zhengmei Xu","doi":"10.1016/j.tranon.2025.102386","DOIUrl":"10.1016/j.tranon.2025.102386","url":null,"abstract":"<div><h3>Background</h3><div>Ovarian cancer represents a significant threat to women's health. and ferroptosis is recognized as a potential natural inhibitor in cancer therapy, the regulatory mechanism of TRIM25 in ovarian cancer and its potential for regulating ferroptosis as a treatment remain unclear.</div></div><div><h3>Methods</h3><div>The role of TRIM25 in ovarian cancer was examined through functional gain- and loss-of-function assays both in vitro and in vivo, while its target genes were identified. The stability and ubiquitination sites of PIEZO1 were analyzed using protein docking and ubiquitination experiments.</div></div><div><h3>Results</h3><div>TRIM25 is highly expressed in ovarian cancer and promotes the growth and metastasis of ovarian cancer cells both in vivo and in vitro. Mechanistically, it facilitates PIEZO1 degradation through ubiquitination-dependent proteasome activity, inhibits ferroptosis, and stimulates ovarian cancer cell growth.</div></div><div><h3>Conclusion</h3><div>Our study clearly shows that TRIM25 stimulates ovarian cancer by inducing K63-linked ubiquitination of PIEZO1, which suppresses ferroptosis and promotes excessive proliferation of ovarian cancer cells. Further research identified the ubiquitination modification site on PIEZO1, providing insights for ovarian cancer treatment.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"56 ","pages":"Article 102386"},"PeriodicalIF":5.0,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143842667","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":"Dynamic predictive power of TP53 signatures in breast cancer prognosis: Pre- and post-neoadjuvant chemotherapy insights","authors":"Keiju Sasaki ,&nbsp;Shin Takahashi ,&nbsp;Kota Ouchi ,&nbsp;Hidekazu Shirota ,&nbsp;Nobuaki Sato ,&nbsp;Kouji Kaneko ,&nbsp;Norikazu Masuda ,&nbsp;Fumiyoshi Fujishima ,&nbsp;Satoko Sato ,&nbsp;Chikashi Ishioka","doi":"10.1016/j.tranon.2025.102398","DOIUrl":"10.1016/j.tranon.2025.102398","url":null,"abstract":"<div><h3>Background</h3><div>The <em>TP53</em> signature determined using a biopsy specimen before neoadjuvant chemotherapy (pre-NAC biopsy specimens) predicts NAC response and prognosis in breast cancer. We aimed to compare the clinical utility of the <em>TP53</em> signature determined using pre-NAC biopsy specimens and surgical specimens after NAC (post-NAC surgical specimens).</div></div><div><h3>Methods</h3><div>This observational cohort study included patients with paired pre-NAC biopsy and post-NAC surgical specimens, analyzing the association between the <em>TP53</em> signature from each specimen and prognosis (UMIN000042055).</div></div><div><h3>Results</h3><div>Pre-NAC biopsy specimens classified 71 patients into those having a <em>TP53</em> mutant signature (pre-mt, <em>n</em> = 47) and wild-type signature (pre-wt, <em>n</em> = 24), with the same for post-NAC surgical specimens (post-mt, <em>n</em> = 16 and post-wt, <em>n</em> = 55). Among the 47 pre-mt patients, 31 became post-wt (pre-mt/post-wt), whereas 16 remained post-mt (pre-mt/post-mt). All pre-wt patients remained post-wt (pre-wt/post-wt). Recurrence-free survival (RFS) was significantly shorter in the pre-mt group than in the pre-wt group, although no significant difference was observed between the post-mt and post-wt groups. Change in the <em>TP53</em> signature following NAC did not affect predictive ability of the <em>TP53</em> signature determined using pre-NAC biopsy specimens.</div></div><div><h3>Conclusions</h3><div>The <em>TP53</em> signature status should be determined using pre-NAC biopsy specimens.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"56 ","pages":"Article 102398"},"PeriodicalIF":5.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143834964","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":"Knockdown TNF family prognosis index crucial gene PDE4B promoted PANoptosis of ovarian carcinoma cell:Based in vitro and in vivo experiments","authors":"Qianqian Yu ,&nbsp;Yunxiao Wang ,&nbsp;Ting Fu ,&nbsp;Dongyu Han ,&nbsp;Linlin Wang ,&nbsp;Lin Zhao ,&nbsp;Yongle Xu","doi":"10.1016/j.tranon.2025.102333","DOIUrl":"10.1016/j.tranon.2025.102333","url":null,"abstract":"<div><div>Ovarian cancer represents a malignancy characterized by high incidence and mortality rates, necessitating further elucidation of its underlying mechanisms. We conducted an analysis using bulk transcriptomic data of ovarian cancer and normal ovarian tissues, as well as single-cell sequencing data according to publicly available databases. Through calculation of Gene Set Variation Analysis (GSVA) scores for TNF family genes, weighted gene co-expression network analysis (WGCNA) for hub genes identification, and subsequent Gene Ontology (GO) enrichment analysis, we delineated pathways crucial in ovarian cancer pathogenesis. Furthermore, differential expression gene analysis facilitated the identification of genes with pronounced expression levels in tumor tissues and their intersection with hub genes, followed by GO analyses across molecular functions (MF), cellular components (CC), and biological processes (BP). Utilizing multivariable Cox regression and LASSO analyses, we constructed a prognostic model comprising 14 genes (GFPT2, PDE4B, PODNL1, TGFBI, CSF1R, PTGIS, SFRP2, COL5A2, TRAC, SLAMF7, VCAN, GBP1P1, C2, TRBV28). Both training and validation sets demonstrated robust diagnostic and prognostic capabilities. Clinical information and immune cell infiltration analyses were further conducted based on the model. In the single-cell sequencing analysis, reducing dimensional complexity and classifying cell types were performed, followed by exploration of gene expression patterns within each subtype and investigation of temporal expression variations across cell subtypes. Biological functional exploration and drug sensitivity analyses were also conducted. Our study contributes novel insights and theoretical foundations for prognosis, treatment, and development of drugs in patients.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"56 ","pages":"Article 102333"},"PeriodicalIF":5.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143838892","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}