Translational Oncology最新文献

{"title":"An emerging melody composed of the notes from structural variants - Comment on ‘The fusion characteristics of RET fusion in pan-cancer among the Chinese population: A comprehensive genomic analysis’ by Chen et al","authors":"Lv Wu,&nbsp;Qing Zhou,&nbsp;Chang Lu","doi":"10.1016/j.tranon.2025.102508","DOIUrl":"10.1016/j.tranon.2025.102508","url":null,"abstract":"<div><div>The identification of <em>RET</em> fusions has significantly advanced precision medicine in lung cancer; however, understanding of the structural features is limited. This commentary discusses a recent comprehensive study by Chen et al. analyzing <em>RET</em> fusions in a large Chinese pan-cancer cohort using DNA and RNA sequencing. We highlight its contribution to understanding fusion structure, diagnostic implications, and differences between Asian and Western populations, setting the stage for future research directions.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"61 ","pages":"Article 102508"},"PeriodicalIF":5.0,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145105599","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":"Disulfidptosis-associated gene signature predicts prognosis and radioresistance in NSCLC","authors":"Jianmin Liu ,&nbsp;Juan Wang ,&nbsp;Jia Wang ,&nbsp;Meng Wu ,&nbsp;Jinming Yu ,&nbsp;Dawei Chen","doi":"10.1016/j.tranon.2025.102496","DOIUrl":"10.1016/j.tranon.2025.102496","url":null,"abstract":"<div><h3>Background</h3><div>NSCLC has an extremely high mortality rate, and limitations exist in the efficacy of current therapeutic modalities and the choice of treatment strategies. Cells overexpressing cystine/glutamate transporter proteins and experiencing a glucose shortage could lead to NADPH deficiency and excessive disulfide buildup, causing stress responses and cell death, which affects patient’s prognosis.</div></div><div><h3>Methods and materials</h3><div>Based on TCGA and GEO datasets, consensus clustering of NSCLC patients was performed to identify disulfidptosis-related genes and construct a prognostic model. The predictive ability of the model was validated in multiple datasets. Survival analysis, genomic mutations, and immune infiltration were used to characterize epigenetic alterations in different risk groups. Multiple radiotherapy-associated NSCLC datasets and radioresistant cell lines were employed to explore the relationship between disulfidptosis-related genes and radiotherapy.</div></div><div><h3>Results</h3><div>We identified nine disulfidptosis-associated prognostic genes (DAPGs) and calculated the disulfidptosis-relevant risk score (DRRS). The risk groups showed a difference in prognosis, genomic mutations, and immune infiltration. CAFs and epithelial-mesenchymal transition significantly enriched in the high DRRS group. The prognostic model also effectively predicted the prognosis of patients receiving radiotherapy, and expression of DAPGs, especially KIF14, is strongly associated with DNA damage and repair, and high expression of KIF14 was observed in radioresistant cells.</div></div><div><h3>Conclusions</h3><div>Our findings imply that a prognostic model related to disulfidptosis could distinguish the prognostic differences among patients, allowing for more personalized treatment strategies. The mechanisms of KIF14 may provide a basis for combating radioresistance and a better understanding of the interaction between disulfidptosis and radiotherapy.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"61 ","pages":"Article 102496"},"PeriodicalIF":5.0,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144865578","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":"CREB binding protein (CREBBP): Structure-based perspectives for the development of clinical inhibitors","authors":"Rongxing Liu ,&nbsp;Jiaxin Li ,&nbsp;Qing Nian ,&nbsp;Gao Tu ,&nbsp;Zhenqiang Wang ,&nbsp;Rong Zhang ,&nbsp;Guobing Li","doi":"10.1016/j.tranon.2025.102507","DOIUrl":"10.1016/j.tranon.2025.102507","url":null,"abstract":"<div><div>Acetylation is an essential process in biological processes. In tissues, protein acetylation occurs mainly at lysine (K) residues. The balance between acetylation and deacetylation is under the control of two enzyme families, histone acetyltransferase (HAT) and histone deacetylase (HDAC), respectively. Although there are many highly selective and potent HDAC inhibitors (such as romidepsin and belinostat), few HAT inhibitors are undergoing clinical trials. CREBBP, also known as CBP, is a member of the HAT family and plays a key role in several diseases, especially in hematopoietic malignancies, through the modulation of different signaling pathways. Studies have shown that CBP is highly expressed and activated in a variety of different tumors; therefore, its inhibitors have attracted increasing research attention. In this review, we discuss the importance of the structure of CBP in the development of potential inhibitors to provide a reference for the development of new selective CBP inhibitors.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"61 ","pages":"Article 102507"},"PeriodicalIF":5.0,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144860967","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":"High-dose furmonertinib plus bevacizumab in EGFR-mutant non-small cell lung cancer with brain metastases after resistance to third-generation EGFR-TKIs: A retrospective study","authors":"Yin Pan ,&nbsp;Meichen Li ,&nbsp;Mingjie Yu,&nbsp;Jing Chen,&nbsp;Hui Yu,&nbsp;Kaijing Liu,&nbsp;Likun Chen","doi":"10.1016/j.tranon.2025.102500","DOIUrl":"10.1016/j.tranon.2025.102500","url":null,"abstract":"<div><h3>Introduction</h3><div>Third-generation EGFR tyrosine kinase inhibitors (TKIs) have improved outcomes in EGFR-mutant non–small cell lung cancer (NSCLC), but resistance occurs, especially in patients with Brain metastases (BMs). Antiangiogenic therapy may enhance CNS drug delivery and EGFR-TKI efficacy​. We evaluated the efficacy of high-dose furmonertinib plus bevacizumab in patients with BMs after third-generation EGFR-TKI failure.</div></div><div><h3>Methods</h3><div>We conducted a single-center retrospective study in EGFR-mutant NSCLC patients with BMs (leptomeningeal and/or parenchymal) who had progressed after ≥1 third-generation EGFR-TKI. Patients received furmonertinib 160 mg daily plus bevacizumab 7.5 mg/kg every 3 weeks until progression or unacceptable toxicity. Primary endpoints were intracranial and overall progression-free survival (iPFS, PFS); secondary endpoints were intracranial and systemic objective response rates (iORR, ORR) and safety.</div></div><div><h3>Results</h3><div>Among the 78 enrolled patients (median follow-up: 11.8 months), median iPFS and PFS were 7.2 months (95 % CI: 5.6–10.5) and 5.85 months (95 % CI: 4.6–7.4), respectively. The iORR was 37.1 %, and ORR was 28.6 %. OS data remain immature at the time of analysis. In patients with both parenchymal and leptomeningeal metastases (n = 47), median iPFS was 7.63 months (95 % CI: 5.0–10.8), and median PFS was 5.7 months (95 % CI: 4.5–10.0); iORR and ORR were 40.5 % and 34.2 %, respectively. In the parenchymal-only subgroup (n = 31), median iPFS and PFS were 7.20 months (95 % CI: 5.5–NR) and 6.4 months (95 % CI: 4.4–11.3), iORR and ORR were 32 % and 20 %. In multivariate analysis, EGFR exon 19 deletion was independently associated with prolonged iPFS (HR = 0.32, P = 0.011) and PFS (HR = 0.47, P = 0.047). CNS radiotherapy administered during treatment also emerged as an independent prognostic factor for both iPFS (HR = 0.34, P = 0.022) and PFS (HR = 0.40, P = 0.018).</div></div><div><h3>Conclusion</h3><div>In this retrospective study, high-dose furmonertinib combined with bevacizumab demonstrated favorable intracranial and systemic activity with an acceptable safety profile in EGFR-mutant NSCLC patients with CNS metastases after resistance to third-generation EGFR-TKIs. These findings provide preliminary evidence supporting the potential clinical benefit of this chemotherapy-sparing strategy. Importantly, these findings warrant further validation in biomarker-stratified prospective trials to guide patient selection and optimize treatment outcomes.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"61 ","pages":"Article 102500"},"PeriodicalIF":5.0,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144860968","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":"TIMELESS deficiency sensitizes thyroid cancer to cisplatin treatment via the DNA damage repair pathway","authors":"Chaoyu Wang ,&nbsp;Ping Yuan ,&nbsp;Dai Yang ,&nbsp;Boke Liu ,&nbsp;Juyong Liang","doi":"10.1016/j.tranon.2025.102504","DOIUrl":"10.1016/j.tranon.2025.102504","url":null,"abstract":"<div><h3>Background</h3><div>The circadian rhythm plays a crucial role in thyroid cancer progression. DNA damage repair (DDR) pathways are closely associated with the sensitivity to cisplatin. However, the role of circadian rhythm genes on cisplatin resistance in thyroid cancer remains undefined.</div></div><div><h3>Methods</h3><div>Panels of molecular screening were achieved by signaling antibody array. Molecular expressions were established <em>via</em> western blotting and polymerase chain reaction (PCR). Multiple assays (Cell Counting Kit-8, colony formation, Transwell) were used to assess cellular dynamics. The xenograft tumor model was employed for <em>in vivo</em> therapeutic evaluation.</div></div><div><h3>Results</h3><div>BCPAP and KTC-1 cells were more resistant to cisplatin than other thyroid cancer cell lines, and DDR pathway activation was detected upon cisplatin treatment in BCPAP and KTC-1. The target that affects cisplatin efficacy was screened among circadian rhythm genes, and found that TIMELESS expression was correlated with the sensitivity to cisplatin and malignant signatures of thyroid cancer. TIMELESS knockdown impaired the DDR pathway activation, and significantly enhanced the efficacy of cisplatin treatment <em>in vitro</em> and <em>in vivo</em>.</div></div><div><h3>Conclusions</h3><div>The newly identified signaling involving circadian rhythm genes and DDR pathways provided mechanistic insights into the cisplatin sensitization strategy in thyroid cancer. Therefore, TIMELESS may be a promising target in thyroid cancer therapeutics.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"61 ","pages":"Article 102504"},"PeriodicalIF":5.0,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144853009","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":"m5C modification of LINC01082 inhibits osteosarcoma progression by modulating the miR-543-TNRC6A axis","authors":"Yawei Hu ,&nbsp;Jiawen Wu ,&nbsp;Huaping Zeng ,&nbsp;Jianhua Zhou ,&nbsp;Ming Gong ,&nbsp;Zengfeng Guo ,&nbsp;Wang Zhang ,&nbsp;Ningfeng Zhang ,&nbsp;Hao Zhang","doi":"10.1016/j.tranon.2025.102502","DOIUrl":"10.1016/j.tranon.2025.102502","url":null,"abstract":"<div><h3>Background</h3><div>Osteosarcoma (OS) is a highly malignant bone tumor primarily affecting children and adolescents, with a significant portion of patients developing metastasis, leading to poor prognosis. Recent studies have identified long noncoding RNAs (lncRNAs) as critical regulators in cancer progression. Among these, LINC01082 has shown tumor-suppressive roles in various cancers, but its function and regulatory mechanisms in OS remain unclear.</div></div><div><h3>Methods</h3><div>We investigated the expression patterns and biological functions of LINC01082 in OS tissues and cell lines using RT-qPCR, western blotting, and cell viability assays. The regulatory impact of 5-methylcytosine (m5C) RNA modification on LINC01082 stability was assessed through MeRIP-qPCR, RNA immunoprecipitation (RIP), and CRISPR/dCas13b-NSUN2-mediated m5C targeting. We further explored the interaction between LINC01082, miR-543, and TNRC6A within RNA-induced silencing complexes (RISCs) using luciferase reporter assays, RNA pull-down, and functional assays.</div></div><div><h3>Results</h3><div>LINC01082 was significantly downregulated in OS tissues and cell lines, with lower expression levels correlating with poorer patient survival. M5C modification, mediated by NSUN2, stabilized LINC01082 through its interaction with the m5C reader protein YBX1. CRISPR/dCas13b-NSUN2-mediated m5C targeting increased LINC01082 expression, resulting in reduced OS cell proliferation and migration, and increased apoptosis. Further, LINC01082 was found to positively regulate TNRC6A expression, with miR-543 modulating this interaction within RISCs. Inhibition of TNRC6A reversed the tumor-suppressive effects of LINC01082 methylation, highlighting the functional significance of the LINC01082-TNRC6A axis in OS.</div></div><div><h3>Conclusion</h3><div>Our study highlights a novel m5C-dependent regulatory mechanism of LINC01082, and demonstrates the potential of CRISPR/dCas13b-NSUN2–mediated m5C editing to functionally modulate this lncRNA and suppress osteosarcoma progression.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"61 ","pages":"Article 102502"},"PeriodicalIF":5.0,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144842575","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":"Cutaneous extranodal NK/T cell lymphoma: heterogeneity of spatial transcriptomic profiling according to primary tumor site","authors":"Myoung Eun Choi ,&nbsp;Hee Joo Yang ,&nbsp;Ji Hun Choi ,&nbsp;Ik Jun Moon ,&nbsp;Joon Min Jung ,&nbsp;Chong Hyun Won ,&nbsp;Sung Eun Chang ,&nbsp;Mi Woo Lee ,&nbsp;Woo Jin Lee","doi":"10.1016/j.tranon.2025.102503","DOIUrl":"10.1016/j.tranon.2025.102503","url":null,"abstract":"<div><h3>Introduction</h3><div>Extranodal NK/T-cell lymphoma (ENKTL) with cutaneous involvement can be divided into primary cutaneous ENKTL (pcENKTL) and secondary cutaneous involvement (scENKTL). Despite different originations, the clinical <strong>and</strong> histopathological findings are indistinguishable. Moreover, the prognosis determinants in each entity have yet to be established. We investigated differences in spatially resolved transcriptome profiles between pcENKTL and scENKTL.</div></div><div><h3>Materials and methods</h3><div>Seven samples with 24 regions of interest were selected for pcENKTCL and scENKTL, using CD56 and CD3 morphology markers.</div></div><div><h3>Results</h3><div>In CD56-positive tumor cell areas, we detected 91 upregulated differentially expressed genes (DEGs) and 27 downregulated DEGs in pcENKTL compared with scENKTL. Protein–protein interaction network revealed significant enrichment of interferon signaling, T cell receptor signaling, and programmed cell death in pcENKTL. Moreover, significant enrichment of translation pathways and nonsense-mediated decay in scENKTL was observed. In immune cell areas, myeloid dendritic cell (p = 0.044) and M1 macrophage (p = 0.039) numbers were increased in pcENKTL. Conversely, neutrophil (p = 0.030) and M2 macrophage (p = 0.030) numbers were increased in scENKTL. We found an increased immune response and antigen presentation in pcENKTL with complete remission, while pcENKTL with progressive disease showed increased angiogenesis. Alternatively, scENKTL with long survival showed increased HLA expression and CD8 memory T cells and M1 macrophages, while scENKTL with short survival showed increased cancer-associated fibroblasts and <em>BIRC5</em>.</div></div><div><h3>Conclusion</h3><div>Overall, the differences in transcriptomic expression and tumor microenvironment between pcENKTL and scENKTL, as well as subgroups based on the prognosis could widen our understanding of the biological characteristics of ENKTL.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"61 ","pages":"Article 102503"},"PeriodicalIF":5.0,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144842576","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":"Exosomal gene signature in esophageal carcinoma: Insights from single-cell and bulk RNA sequencing","authors":"Hui Li,&nbsp;Pei Huang,&nbsp;YunJiao Wang,&nbsp;Min Zhang,&nbsp;DongLing Gao","doi":"10.1016/j.tranon.2025.102490","DOIUrl":"10.1016/j.tranon.2025.102490","url":null,"abstract":"<div><div>Esophageal squamous cell carcinoma (ESCA) remains a lethal disease with few reliable biomarkers for early diagnosis or treatment selection. In this study, we combined bulk RNA-seq (TCGA-ESCA, GSE53625) and single-cell RNA-seq (GSE196756) data to derive and characterize an exosome-related gene signature. Using LASSO-Cox regression on 121 literature-curated exosomal genes, we established a nine-gene risk model that stratified ESCA patients into high- and low-risk groups with significantly different overall survival. This signature was validated computationally in two independent bulk cohorts and shown to correlate with established clinical parameters. Functional assays for one model component, HAPLN3, confirmed its tumor-suppressive role: HAPLN3 overexpression inhibited ESCA cell proliferation and promoted apoptosis. To explore immunotherapy relevance, we analyzed anti–PD-L1 response in the IMvigor210 bladder cancer cohort—chosen because of shared squamous histology and PD-L1 pathways—to show that low-risk patients exhibited higher response rates and longer survival. Finally, single-cell analysis mapped each signature gene to specific tumor microenvironment compartments, and integrative genomic profiling linked risk scores to copy number variation and DNA methylation changes. Together, our findings define a functionally informed exosomal biomarker panel for ESCA prognosis and suggest its potential to guide immunotherapy, with further validation in ESCA-specific immunotherapy cohorts underway.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"61 ","pages":"Article 102490"},"PeriodicalIF":5.0,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144842574","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":"\"A novel approach to understanding the role of TCF3 mutations in childhood B-cell precursor acute lymphoblastic leukemia\"","authors":"Monika Lejman ,&nbsp;Aleksandra Ozygała ,&nbsp;Kinga Wróblewska ,&nbsp;Weronika Zegardło ,&nbsp;Paulina Widz ,&nbsp;Martyna Żyła","doi":"10.1016/j.tranon.2025.102505","DOIUrl":"10.1016/j.tranon.2025.102505","url":null,"abstract":"<div><div>The <em>TCF3</em> (also known as <em>E2A</em>) gene is responsible for encoding a critical transcriptional factor that plays a pivotal role in the differentiation of lymphoid progenitor cells. The <em>TCF3</em> has been implicated in chromosomal translocations involving various genes, including <em>PBX1, HLF</em>, and <em>ZNF384</em>, as evidenced by recent clinical case studies (rare occuring). These include <em>TLX1, FLI1</em>, and <em>TEF</em>. These rearrangements have been observed to result in uncontrollable proliferation and development of B-cell progenitor acute lymphoblastic leukemia (BCP-ALL). The 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumors distinguishes B-cell lymphoblastic leukemia/lymphoma with TCF3 rearrangement into two types: with <em>TCF3</em>::<em>PBX1</em> fusion and <em>TCF3</em>::<em>HLF</em> fusion. TCF3-positive pediatric BCP-ALL accounts for 5-11% of patients, making TCF3 an essential component of diagnostic panels for this leukemia. The objective of this manuscript is to provide a comprehensive description of the known <em>TCF3</em> rearrangements and their associated gene partners. The review will also address the impact of <em>TCF3</em> fusion genes in pediatric ALL according to the latest data and modern treatments, including the latest research results of Children’s Oncology Group from the 66th American Society of Hematology (ASH) and promising biomarker in B-ALL - circular RNA with regard to <em>TCF3</em> rearrangements. Additional genetic alterations, termed \"secondary hits\" are involved in lymphoid development and pathogenesis of ALL. The most frequently observed rearrangements in <em>TCF3</em> are: <em>PAX5, IKZF1, SETDB2, EBF1</em>, as well as <em>CDKN2A/B</em>.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"61 ","pages":"Article 102505"},"PeriodicalIF":5.0,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144829762","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":"Novel gene rearrangement leads to altered expression of Hornerin in sensitive and chemoresistant ovarian cancer","authors":"Ghassan M. Saed ,&nbsp;Harvey Sharma ,&nbsp;Jenna Dabaja ,&nbsp;Asad Nawaz ,&nbsp;Ayesha Alvero ,&nbsp;Robert T. Morris ,&nbsp;Asma Basha ,&nbsp;Lucas Werner ,&nbsp;Toshima Z. Parris ,&nbsp;Khalil Helou","doi":"10.1016/j.tranon.2025.102495","DOIUrl":"10.1016/j.tranon.2025.102495","url":null,"abstract":"<div><h3>Background</h3><div>Hornerin (HRNR) is part of the S100-fused protein family and has been linked to poorer prognosis in various cancers, though the mechanisms remain unclear. This study aimed to explore the role of HRNR in ovarian cancer.</div></div><div><h3>Methods</h3><div>We conducted proteomic analysis (<em>n</em> = 252) and RNA sequencing (<em>n</em> = 96) on primary ovarian carcinomas to evaluate HRNR expression across different histotypes, survival outcomes, and to identify genetic variants in the HRNR gene. We also assessed HRNR levels in both chemosensitive and chemoresistant ovarian cancer cell lines, as well as in serum samples at different disease stages.</div></div><div><h3>Results</h3><div>Our findings revealed that HRNR levels were significantly higher in clear cell and mucinous ovarian carcinomas compared to high-grade serous carcinomas, with elevated expression associated with shorter survival. Additionally, HRNR levels increased in sera from late-stage patients compared to those in early stages. We identified several potentially harmful genetic variants in exon 3 of HRNR in patients with high-grade serous carcinoma, including a translocation of a 900 bp fragment from exon 3 to a region between exons 1 and 2. Chemoresistant ovarian cancer cells exhibited higher HRNR levels than chemosensitive cells. Silencing HRNR using siRNA markedly enhanced the cytotoxic effects on all tested ovarian cancer cells.</div></div><div><h3>Conclusions</h3><div>HRNR plays a significant role in ovarian cancer with potential to serve as a prognostic marker. Additionally, targeting HRNR expression may offer therapeutic benefits, particularly for patients with chemoresistance or specific HRNR genetic variants, highlighting the need for further investigation in the management of ovarian cancer.</div></div><div><h3>Significance</h3><div>Hornerin (HRNR) is linked to poor prognosis in various cancers, but its role in ovarian cancer has been underexplored. Our study shows that HRNR expression is significantly higher in clear cell and mucinous ovarian carcinomas compared to high-grade serous carcinomas, correlating with shorter survival. Elevated HRNR levels in late-stage patients suggest its potential as a prognostic marker. We also identified harmful genetic variants in HRNR, including a novel translocation, which may affect disease progression. Targeting HRNR could enhance chemotherapy effectiveness, particularly for patients with HRNR genetic variants, positioning it as a promising biomarker and therapeutic target in ovarian cancer.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"61 ","pages":"Article 102495"},"PeriodicalIF":5.0,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144829763","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}