Translational Oncology最新文献

{"title":"Poly-ADP-ribosylation modulated by poly(ADP-ribose) polymerase 1 is associated with glucose metabolism in colorectal cancer cells","authors":"Chenxuan Zhang ,&nbsp;Peng Wang ,&nbsp;Jia Yu ,&nbsp;Jianhui Yuan ,&nbsp;Lilong Zhang ,&nbsp;Man Li","doi":"10.1016/j.tranon.2025.102623","DOIUrl":"10.1016/j.tranon.2025.102623","url":null,"abstract":"<div><div>The preference of cancer cells to generate energy from glycolysis for rapid cell proliferation is called the Warburg effect. Poly(ADP-ribose) polymerase 1 (PARP1) performs various cellular functions, including poly-ADP-ribosylation and DNA repair. In the present study, we investigated the novel effects and mechanisms of PARP1 inhibition on glucose metabolism in colorectal cancer cells under hypoxia. We subjected Caco-2 and LoVo cancer cell lines to a concentration gradient of PARP1 inhibitor in a hypoxic environment induced with a tri-gas incubator (5 % CO₂, 1 % O₂, 94 % N₂). Inhibiting PARP1 activation attenuated Poly-ADP-ribosylation, increasing the NAD⁺/NADH ratio. High concentrations of PARP1 significantly reduced the glucose consumption rate of the treated cells, while PARP1 inhibition depressed cell progression in a concentration-dependent manner. The expression of hypoxia-inducible factor-1α (HIF-1α), hexokinase 2 (HK2), and glucose transporter 1 (GLUT-1), critical for the Warburg effect and glucose metabolism, was considerably reduced after the inhibitor treatments. Moreover, inhibiting PARP1 activation reduced phosphorylated AKT (p-AKT) and mTOR (p-mTOR) levels. In conclusion, our study revealed that PARP1 inhibition decelerates the Warburg effect in colorectal cancer cells, likely through the AKT/mTOR/HIF-1α pathway.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"63 ","pages":"Article 102623"},"PeriodicalIF":5.0,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145678790","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 PI3K pathway is a downstream effector of NRF2 activation in the esophagus","authors":"Boopathi Subramaniyan ,&nbsp;Yahui Li ,&nbsp;Zhaohui Xiong ,&nbsp;Chorlada Paiboonrungruang ,&nbsp;Candice Bui-Linh ,&nbsp;Francis Spitz ,&nbsp;Xiaoxin Chen","doi":"10.1016/j.tranon.2025.102629","DOIUrl":"10.1016/j.tranon.2025.102629","url":null,"abstract":"<div><div>Mutations in nuclear factor erythroid 2–related factor 2 (<em>NFE2L2</em> or <em>NRF2</em>) occur in 10–22 % of esophageal squamous cell carcinoma (ESCC) cases and result in NRF2 activation, promoting tumor progression, and therapeutic resistance. Although previous studies suggested a link between NRF2 and kinases, specific kinases responsive to NRF2 activation remain to be fully identified. Using protein phosphorylation profiling and kinase activity profiling, we identified phosphatidylinositol 3-kinase (PI3K) pathway as a downstream effector in NRF2^W24C-KYSE70 cells compared to isogenic NRF2^null-KYSE70 cells. AREG, pEGFR, PIK3CA, pAKT, p-S6, and p-PTEN were downregulated in NRF2 deficient cells. Notably, NRF2 deficiency sensitized ESCC cells to EGFR, PIK3CA, and AKT inhibitors. Co-treatment with Alpelisib (a PIK3CA inhibitor) and Pyrimethamine (an NRF2 inhibitor) synergistically suppressed the growth of NRF2^W24C-KYSE70 and NRF2^D77V-KYSE180 cells. <em>In vivo</em>, NRF2 activation in the esophageal epithelium of <em>Keap1^-/-</em> and <em>Sox2CreER;LSL-Nrf2^E79Q/+</em> mice resulted in upregulation of pAKT, p-mTOR, and pS6. In human ESCC tissues, expression of pNRF2 (an active form of NRF2) was positively associated with that of pAKT and p-mTOR. Furthermore, co-treatment with Pyrimethamine and Alpelisib significantly inhibited hyperproliferation and hyperkeratinization in the esophageal epithelium of <em>Sox2CreER;LSL-Nrf2^E79Q/+</em>mice. Together, our data demonstrates the PI3K pathway as a downstream effector of NRF2 activation in the esophagus, and co-targeting of NRF2 and the PI3K pathway may offer a promising therapeutic strategy for NRF2^Mut ESCC.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"63 ","pages":"Article 102629"},"PeriodicalIF":5.0,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145678825","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":"piR-43452 suppresses bladder cancer progression and enhances gemcitabine sensitivity via GTSF1/PIWIL4-mediated LRP1 mRNA destabilization","authors":"Yuchen Shi ,&nbsp;Jiazhu Sun ,&nbsp;Kai Yu ,&nbsp;Dingheng Lu,&nbsp;Xinyang Niu,&nbsp;Yuxiao Li,&nbsp;Suyuelin Huang,&nbsp;Jindan Luo,&nbsp;Xiao Wang,&nbsp;Xueyou Ma,&nbsp;Jiangfeng Li,&nbsp;Yufan Ying,&nbsp;Liping Xie,&nbsp;Ben Liu","doi":"10.1016/j.tranon.2025.102626","DOIUrl":"10.1016/j.tranon.2025.102626","url":null,"abstract":"<div><div>Piwi-interacting RNAs (piRNAs), while crucial for genomic integrity in germline cells, remain poorly characterized in somatic cancers. This study identifies piR-43452 as a significantly downregulated piRNA in bladder cancer (BCa), with loss of expression correlating clinically with muscle invasion and lymph node metastasis. Through assays <em>in vitro</em> and <em>in vivo</em>, we demonstrate that piR-43452 acts as a potent tumor suppressor, inhibiting BCa cell proliferation, migration, and xenograft growth while promoting apoptosis. Mechanistically, we identified that piR-43452 directly binds the 3′UTR of LRP1 mRNA and recruits the GTSF1/PIWIL4 complex, which enhances target cleavage through GTSF1-dependent conformational activation. This post-transcriptional regulation led to significant LRP1 suppression, subsequently inhibiting proliferation and restoring chemosensitivity. Our findings establish a novel piRNA-guided mechanism for overcoming chemoresistance and suggest that targeting the piR-43452/GTSF1/PIWIL4/LRP1 axis may provide therapeutic benefit in gemcitabine-resistant BCa.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"63 ","pages":"Article 102626"},"PeriodicalIF":5.0,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145678706","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 roadmap to unveil the mechanism(s) of natural indole-derived molecules against NAFLD-derived HCC via systems pharmacology","authors":"Ki-Kwang Oh ,&nbsp;Goo-Hyun Kwon,&nbsp;Kyeong Jin Lee,&nbsp;Jung-A Eom ,&nbsp;Dong Joon Kim,&nbsp;Ki-Tae Suk","doi":"10.1016/j.tranon.2025.102618","DOIUrl":"10.1016/j.tranon.2025.102618","url":null,"abstract":"<div><h3>Background</h3><div>Non-alcoholic fatty liver disease (NAFLD) is involved in non-alcoholic steatohepatitis (NASH), liver cirrhosis (LC), and even hepatocellular carcinoma (HCC). Hence, this study was to elucidate nuanced key mechanism(s), target(s), and Natural Indole-Derived Molecules (NIDMs) against NAFLD-derived HCC.</div></div><div><h3>Methods</h3><div>The NIDMs were retrieved by Natural Product Activity &amp; Species Source Database (NPASS). The protein-protein interaction (PPI) networks, bubble plot on key signaling pathways, etiological spectrum-signaling pathways-targets-indoles (ESTI) networks, the verification of toxicity on key NIDMs, and MDE (Molecular Docking Evaluation) were performed with integrating perspective.</div></div><div><h3>Results</h3><div>The 141 NIDMs were identified by NPASS and SwissADME, suggesting that the NIDMs were associated with Similarity Ensemble Approach (SEA; 845 targets) and SwissTargetPrediction (STP; 1107 targets). On PPI analysis, JUN was the uppermost target with the highest DV (Degree Value). A bubble plot based on rich factor constructed to identify key mechanism(s), suggesting that AGE-RAGE signaling pathway in diabetic complications might be key antagonistic mode to hinder the spontaneous progression of NAFLD. The key targets were JUN, and AGTR1 on AGE-RAGE signaling pathway in diabetic complications, binding most stably to Marinacarboline D, and Fumitremorgin F, respectively.</div></div><div><h3>Conclusions</h3><div>In closing, this study provides critical insights into the key mechanisms, targets, and NIDMs that may impede etiological spectrum of NAFLD.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"63 ","pages":"Article 102618"},"PeriodicalIF":5.0,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145678674","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 CHPT-pSTAT3-SLC7A11 signaling axis controls progression and ferroptosis susceptibility of pancreatic cancer","authors":"Jianhui Yang ,&nbsp;Jiang Liu ,&nbsp;Zeyin Rong ,&nbsp;Zhen Tan ,&nbsp;Wei Wang ,&nbsp;Qingcai Meng ,&nbsp;Miaoyan Wei ,&nbsp;Jie Hua ,&nbsp;Bo Zhang ,&nbsp;Xianjun Yu ,&nbsp;Jin Xu ,&nbsp;Chen Liang","doi":"10.1016/j.tranon.2025.102624","DOIUrl":"10.1016/j.tranon.2025.102624","url":null,"abstract":"<div><h3>Background</h3><div>Pancreatic ductal adenocarcinoma (PDAC) exhibits profound chemoresistance and metastasis, driving its dismal prognosis. Gemcitabine (GEM) resistance remains a critical barrier, necessitating exploration of metabolic regulators like choline phosphotransferase 1 (CHPT1) and ferroptosis in PDAC therapy.</div></div><div><h3>Method</h3><div>GEM-resistant PDAC cells were generated through stepwise induction. Metabolomics, RNA sequencing, and functional assays (CCK-8, EdU, Transwell) identified CHPT’s role. CHPT1 and SLC7A11 were genetically modulated using lentiviral vectors. Xenograft models assessed tumor growth.</div></div><div><h3>Results</h3><div>CHPT1 was downregulated in PDAC tissues and GEM-resistant cells. Restoring CHPT1 suppressed proliferation, migration, and epithelial–mesenchymal transition while enhancing GEM sensitivity. Mechanistically, CHPT1 recruited phosphatase PTPN1 to dephosphorylate STAT3 at Y705, inhibiting SLC7A11 transcription and triggering ferroptosis via lipid peroxidation. PTPN1 knockdown abolished CHPT1’s tumor-suppressive effects. Combining ferroptosis inducers (e.g., Erastin) with GEM synergistically inhibited tumor growth in vitro and in vivo.</div></div><div><h3>Conclusion</h3><div>The CHPT1-pSTAT3-SLC7A11 axis governs ferroptosis-dependent chemoresistance in PDAC. Dual targeting of CHPT1 and ferroptosis pathways represents a promising strategy to overcome GEM resistance, highlighting metabolic-kinase crosstalk as a therapeutic vulnerability.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"63 ","pages":"Article 102624"},"PeriodicalIF":5.0,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145669829","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":"From benchside avatars to bedside breakthroughs: Patient-derived organoids in the new era of cancer immunotherapy","authors":"Zhihui Mi ,&nbsp;Hui Guan ,&nbsp;Guodong Zhang ,&nbsp;Dongyang Li ,&nbsp;Yang Yu ,&nbsp;Jialin Qu","doi":"10.1016/j.tranon.2025.102619","DOIUrl":"10.1016/j.tranon.2025.102619","url":null,"abstract":"<div><div>The success of cancer immunotherapy is hampered by the lack of dynamic models that can predict patient-specific responses and guide the development of novel treatments. Static biomarkers, such as PD-L1 expression and tumor mutational burden, often fail to capture the complexity of the tumor-immune dialogue. Patient-derived tumor organoids (PDTOs) have emerged as a revolutionary ex vivo platform that bridges this gap. This review outlines the evolution of PDTOs from simple epithelial cultures to sophisticated, immune-competent \"avatars\" that faithfully recapitulate the patient's tumor microenvironment (TME). We critically discuss the key methodologies for reconstructing the TME, including \"add-in\" co-culture systems with diverse immune and stromal cells (e.g., T-cells, MDSCs, CAFs, neutrophils) and \"all-in-one\" approaches that preserve the native immune ecosystem. Furthermore, we highlight the expanding role of these advanced models beyond predicting checkpoint inhibitor efficacy. We showcase their groundbreaking applications as core development platforms for next-generation immunotherapies, including CAR-T cell therapy and the validation of personalized neoantigen-based vaccines. While acknowledging the significant translational challenges that remain, we conclude that immune-competent PDTOs represent an indispensable tool poised to accelerate the new era of precision immuno-oncology.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"63 ","pages":"Article 102619"},"PeriodicalIF":5.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145661742","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":"Circular RNA circAHSA1 serves as a stable serum biomarker for the diagnosis and progression of gastric cancer","authors":"Jiayi He ,&nbsp;Shuo Ma ,&nbsp;Shougang Kuai ,&nbsp;Shaoqing Ju","doi":"10.1016/j.tranon.2025.102620","DOIUrl":"10.1016/j.tranon.2025.102620","url":null,"abstract":"<div><h3>Background</h3><div>Gastric cancer (GC) remains a major cause of cancer-related mortality globally, largely due to the absence of reliable non-invasive biomarkers for early detection. Circular RNAs (circRNAs), characterized by covalently closed-loop structures, stability, and detectability in circulation, have emerged as promising liquid biopsy candidates.</div></div><div><h3>Methods</h3><div>circAHSA1 (hsa_circ_0032777) was identified through GEO dataset screening (GSE121445) and validated in GC tissues, serum, and cell lines using qRT-PCR with optimized internal reference selection. Diagnostic performance was assessed using ROC analysis and DeLong tests, evaluating circAHSA1 alone and in combination with CEA, CA199, and CA724. Biological functions were examined through proliferation, apoptosis, migration, and invasion assays. Subcellular localization and potential downstream miRNA interactions were analyzed using nuclear–cytoplasmic fractionation and multi-database bioinformatic prediction.</div></div><div><h3>Results</h3><div>circAHSA1 expression was significantly elevated in GC tissues, serum, and cell lines, and correlated with lymph node metastasis, differentiation status, and TNM stage. Serum circAHSA1 effectively discriminated GC from healthy controls (AUC = 0.787) and gastritis patients (AUC = 0.752), outperforming conventional markers, with statistical superiority confirmed by DeLong analysis. Combined detection further improved diagnostic accuracy (AUC = 0.871). Functionally, silencing circAHSA1 suppressed GC cell proliferation, migration, and invasion while enhancing apoptosis and inducing cell-cycle arrest. Bioinformatic analysis suggested miR-647 and miR-661 as potential downstream targets.</div></div><div><h3>Conclusions</h3><div>circAHSA1 is a stable, GC-specific circulating biomarker with both diagnostic and functional relevance. These findings support circAHSA1 as a promising candidate for liquid biopsy-based GC detection and a potential therapeutic target.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"63 ","pages":"Article 102620"},"PeriodicalIF":5.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145661664","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 prognostic value of tumor macroscopic morphology in colorectal cancer","authors":"Hsinyi Lin ,&nbsp;Zimin Zhao ,&nbsp;Yao Ma ,&nbsp;Xiangchao Shi ,&nbsp;Limei Guo ,&nbsp;Junwei Wang ,&nbsp;Wei Fu ,&nbsp;Xin Zhou","doi":"10.1016/j.tranon.2025.102607","DOIUrl":"10.1016/j.tranon.2025.102607","url":null,"abstract":"<div><h3>Background</h3><div>This study aims to evaluate the prognostic value of tumor macroscopic morphology in colorectal cancer (CRC) and understand the molecular mechanism behind different tumor morphologies.</div></div><div><h3>Methods</h3><div>642 eligible patients were enrolled in this study, including 335 patients in the prospective study and 307 patients in the retrospective study. CRCs were categorized into protruded, ulcerative, and infiltrative types according to our morphological classification, and their clinicopathological features and prognosis were analyzed. Furthermore, bulk RNA sequencing, single-cell RNA sequencing (scRNA-seq) and immunohistochemistry were performed to map the tumor microenvironment of different tumor morphologies.</div></div><div><h3>Results</h3><div>In the prospective cohort, CRC with infiltrative type were significantly associated with unfavorable clinicopathological characteristics and poor survival compared with ulcerative type and protruded type. Bulk RNA sequencing revealed that the infiltrative type correlated with higher expression of fibroblast activation protein-α (FAP), periostin and platelet endothelial cell adhesion molecule-1 (PECAM-1), which corresponded with elevated cell proportions of stromal cells and endothelial cells in scRNA-seq. Additionally, a retrospective cohort was conducted to assess the value of preoperative endoscopic morphology and radiological morphology, both independently associated with disease-free survival (DFS).</div></div><div><h3>Conclusion</h3><div>We proposed a revised tumor macroscopic morphology classification system in CRC. The infiltrative type is associated with poorer clinical outcomes, characterized by increased cancer-associated fibroblast (CAF) infiltration and enhanced angiogenesis compared with other types. Importantly, when expanded to endoscopy and CT preoperatively, both endoscopic and radiological morphology can serve as preoperative predictors of DFS.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"63 ","pages":"Article 102607"},"PeriodicalIF":5.0,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145623667","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":"Galectin-7 as a biomarker for aggressiveness and poor prognosis in thymic epithelial tumors","authors":"Yilv Lv ,&nbsp;Zhitao Gu ,&nbsp;Kunping Li ,&nbsp;Teng Mao ,&nbsp;Xuefei Zhang ,&nbsp;Ning Xu ,&nbsp;Wentao Fang ,&nbsp;Qiangling Sun","doi":"10.1016/j.tranon.2025.102612","DOIUrl":"10.1016/j.tranon.2025.102612","url":null,"abstract":"<div><h3>Objective</h3><div>To identify molecular determinants of tumor aggressiveness in TETs and to elucidate their functional roles and underlying mechanisms in tumor progression.</div></div><div><h3>Methods</h3><div>We performed proteomic profiling using data-independent acquisition mass spectrometry on 40 TET samples and their paired adjacent normal tissues to explore potential molecular differences. TETs were stratified into high-risk (WHO types B2, B3, and thymic carcinoma) and low-risk (types A, AB, and B1) groups based on histological classification. Gene set enrichment analysis (GSEA) was applied to the proteomic data to delineate pathways enriched in high-risk tumors. A validation cohort comprising 164 TET patients, along with 6 non-TET controls, was analyzed to assess Galectin-7 expression by immunohistochemistry and to evaluate its prognostic value. To further explore the biological role of Galectin-7, functional assays were performed in Tc1889 cells following Galectin-7 overexpression.</div></div><div><h3>Results</h3><div>Proteomic analysis revealed Galectin-7 as a highly upregulated protein in high-risk TETs. GSEA analysis identified enrichment of mitochondrial and extracellular matrix-related pathways in high-risk tumors. Immunohistochemistry showed Galectin-7 expression in 82 % of high-risk TETs and only 13 % of low-risk TETs (<em>p</em> &lt; 0.001), with higher expression correlating with advanced tumor stage and reduced progression-free survival. Functional assays demonstrated that Tc1889 cells with Galectin-7 overexpression exhibited enhanced proliferation and invasion. Additionally, MAPK signaling pathway activation was observed in Galectin-7-overexpressing cells.</div></div><div><h3>Conclusions</h3><div>Galectin-7 is a potential biomarker for aggressive TETs, with expression levels associated with features of poor prognosis. These findings provide insight into TET biology and support further exploration of Galectin-7 in tumor stratification and therapeutic research.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"63 ","pages":"Article 102612"},"PeriodicalIF":5.0,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145623610","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":"Evaluation of the 1021-HRD assay compared to established HRD testing platforms in ovarian cancer","authors":"Eirini Papadopoulou ,&nbsp;Elena Fountzilas ,&nbsp;Vasiliki Metaxa-Mariatou ,&nbsp;Aikaterini Tsantikidi ,&nbsp;Georgios Tsaousis ,&nbsp;Angeliki Meintani ,&nbsp;Chrysiida Florou-Chatzigiannidou ,&nbsp;Stella Maxouri ,&nbsp;Konstantinos Papazisis ,&nbsp;Theofanis Floros ,&nbsp;Christos Papadimitriou ,&nbsp;Eleni Timotheadou ,&nbsp;Kyriaki Papadopoulou ,&nbsp;Athanasios Papathanasiou ,&nbsp;Dimitrios Grigoriadis ,&nbsp;Xiaorui Fu ,&nbsp;Xunmei Zheng ,&nbsp;Yun Xing ,&nbsp;Xinhua Du ,&nbsp;Andreea Truican ,&nbsp;George Nasioulas","doi":"10.1016/j.tranon.2025.102621","DOIUrl":"10.1016/j.tranon.2025.102621","url":null,"abstract":"<div><div>PARP inhibitors have revolutionized ovarian cancer treatment, with benefits strongly linked to the presence of Homologous Recombination Deficiency (HRD). Although HRD testing was originally conducted on centralized platforms, there is growing demand for scalable, accessible, and robust solutions capable of supporting expanded clinical utilization. In the present study, a decentralized NGS-based assay was compared for its ability to effectively identify HRD positive patients when compared to the reference assay as well as other testing platforms.</div><div>Eighty-two cases of ovarian cancer patients previously tested using the reference HRD assay (Myriad MyChoice® CDx assay) were evaluated by an NGS based HRD assay, the 1021-HRD assay (GenePlus), that provides genomic instability (GI) analysis along with tumor molecular profiling. HRD status, GI status (referred to as HRD-score), and even <em>BRCA1/2</em> mutation detection were assessed for concordance with the reference test and the analytical accuracy of the assay was calculated. Additionally, GI alignment across alternative HRD testing platforms was examined. Finally, the association between key tumor alterations and the HRD status was evaluated.</div><div>The 1021-HRD assay demonstrated an overall HRD classification agreement of approximately 92.68 % (κ = 0.841) in comparison to the reference method, as evidenced by the results, with 81.25 % specificity and 100 % sensitivity. These features generally suggest consistent performance, with only minor discrepancies observed. The <em>BRCA1/2</em> alterations detected were 97.56 % in agreement with the approved assay. The Pearson r value of 0.878 indicates a strong correlation between the GI values obtained. The assay's capacity to detect non-<em>BRCA1/2</em> HRD phenotypes was verified by the observation that 55.56 % of <em>BRCA</em>-wildtype malignancies were HRD-positive. Of particular interest, combining molecular profiling with GI analysis, the assay identified additional actionable alterations in 65 % of the cases, revealing clinically relevant biomarkers beyond the homologous recombination pathway. This wide-ranging approach may provide more diagnostic and therapeutic insight than HRD testing alone.</div><div>In conclusion, the 1021-HRD assay is a dependable, decentralized alternative for HRD testing. It can provide a more comprehensive genomic characterization and exhibits remarkable analytical concordance with current standards. Its combined format and accessibility render it well-suited for real-world use in personalized ovarian cancer care. Its additional capacity to reveal more extensive tumor genomic alterations improves clinical decision-making and underscores the importance of integrating HRD scoring with comprehensive molecular profiling in personalized oncology.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"63 ","pages":"Article 102621"},"PeriodicalIF":5.0,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145623666","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}