Cancer Genetics最新文献

{"title":"First Middle East and North Africa report of an EPCAM–MSH2 deletion in two Iranian Lynch syndrome families: a case report","authors":"Mohammad Sina ,&nbsp;Keivan Majidzadeh-A ,&nbsp;Shiva Zarinfam ,&nbsp;Rosalba Monica Ferraro ,&nbsp;Elena Laura Mazzoldi ,&nbsp;Seyedeh Zahra Mousavi ,&nbsp;Silvia Clara Giliani","doi":"10.1016/j.cancergen.2025.11.010","DOIUrl":"10.1016/j.cancergen.2025.11.010","url":null,"abstract":"<div><div>Lynch syndrome is an inherited autosomal-dominant cancer-predisposition condition that results from germline defects in the DNA mismatch-repair (MMR) pathway or inactivation of the <em>EPCAM</em> gene. Variants involving <em>EPCAM</em> are detected in roughly 1–3 % of Lynch syndrome cases, whereas combined <em>EPCAM–MSH2</em> deletions remain very uncommon. We investigated two Iranian families from the same village, each with multiple members affected by colorectal cancer (CRC), to identify the underlying genetic causes. In Family A, colon tumor immunohistochemistry showed loss of MSH2 and MSH6 expression in formalin-fixed paraffin-embedded tissue. Despite negative Sanger sequencing results for <em>MSH2</em>, whole-exome sequencing (WES) followed by copy number variant (CNV) analysis using CNVkit and ExomeDepth identified a large CNV across <em>EPCAM</em> and <em>MSH2</em>. Breakpoints were confirmed by MLPA and SYBR Green qPCR. A second family from the same village showed multi-generational CRC; Family B was therefore tested by MLPA/qPCR for the same CNV. We identified a heterozygous ∼76.7 kb deletion spanning <em>EPCAM</em> exons 1–9 and <em>MSH2</em> exons 1–8. In Family A, 15/23 tested relatives were carriers; six carriers had CRC at 35–53 years, and no extracolonic tumors were observed. The CRC affected proband of Family B harbored the identical deletion. Cascade testing achieved remarkable uptake, with &gt;20 relatives tested in family A—over tenfold higher than typical reports—facilitated by direct clinician contact and streamlined logistics such as convenient blood collection. This is the first documented <em>EPCAM–MSH2</em> deletion reported from the Middle East and North Africa region (MENA).</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"298 ","pages":"Pages 315-320"},"PeriodicalIF":2.1,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145617932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of somatic variant oncogenicity classification using ClinGen/CGC/VICC guidelines and QIAGEN Clinical Insight Interpret decision support software","authors":"Aarthi Goverdhan ,&nbsp;Lisa Mullineaux ,&nbsp;Amber Pryzbylski ,&nbsp;Claire Teigen ,&nbsp;Kevin C. Halling ,&nbsp;Sheryl K. Elkin ,&nbsp;Beth A. Pitel","doi":"10.1016/j.cancergen.2025.09.009","DOIUrl":"10.1016/j.cancergen.2025.09.009","url":null,"abstract":"<div><div>Accurate clinical interpretation of somatic cancer variants is critical for diagnosis and guidance of precision oncology treatment. As the depth and breadth of genomic sequencing increased, laboratories developed independent standards for the classification of somatic variants. In response, a set of standards for classification were published by a collaboration among Clinical Genome Resource (ClinGen), Cancer Genomics Consortium (CGC) and Variant Interpretation for Cancer Consortium (VICC). This study evaluated these standards and compared the resulting classifications to the classifications generated by a clinical decision support software system, QIAGEN Clinical Insight (QCI) Interpret One, a system using a version of the 2015 consensus guidelines by the American College of Medical Genetics (ACMG) and Association for Molecular Pathology (AMP) customized for somatic assessment. The published variant set for validation was utilized and expanded by conducting a retrospective analysis using real-world cancer variants drawn from oncology cases tested at Mayo Clinic. For “oncogenic” and “likely oncogenic” variants in the combined datasets, automated classifications by the QCI system were 97.2% concordant with those assessed using the ClinGen/CGC/VICC system. The ClinGen/CGC/VICC standards led to more conservative variant classifications, with a larger proportion of variants assigned to the “variant of unknown significance” and “likely benign” designations. This study demonstrates that the ClinGen/CGC/VICC guidelines and clinical decision support tools can be effectively used together to facilitate somatic variant classification and interpretation.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"298 ","pages":"Pages 151-158"},"PeriodicalIF":2.1,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145158113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The prevalence of TP53, APC, and PIK3CA gene mutations in colorectal cancer patients: A Systematic Review and Meta-analysis","authors":"Mobina Gheibi ,&nbsp;Sogand Sadeghi ,&nbsp;Amirhossein Hessami ,&nbsp;Zahra Erfani ,&nbsp;Erfan Ghadirzadeh ,&nbsp;Mahmood Moosazadeh","doi":"10.1016/j.cancergen.2025.10.003","DOIUrl":"10.1016/j.cancergen.2025.10.003","url":null,"abstract":"<div><h3>Background</h3><div>Despite the significant role of genetic mutations in colorectal cancer (CRC), there is considerable variability in the reported prevalence of TP53, APC, and PIK3CA mutations across different populations and CRC subtypes. Thus, this systematic review and meta-analysis aimed to assess the prevalence of TP53, APC, and PIK3CA gene mutations in CRC patients.</div></div><div><h3>Methods</h3><div>A systematic search was done in Medline/PubMed, Scopus, Embase, Web of Science, and Google Scholar from their dates of inception until September 2024. Obsevational studies reported TP53, APC, and PIK3CA mutations in CRC patients were included. The quality of the evidence was assessed using the Joanna Briggs Institute (JBI) instrument. The prevalence of each mutated gene and its 95 % confidence interval (CI) were calculated using the random effects model.</div></div><div><h3>Results</h3><div>A total of 32 studies were included comprising 7765 participants with JBI scores ranging from 7 to 9. Our findings showed that TP53 mutations were the most prevalent, detected in 51 % (95 % CI: 41–60) of cases, with a significantly higher prevalence in M-CRC (81 %, 95 % CI: 76–85), followed by APC (33 %, 95 % CI: 13–52), and PIK3CA (19 %, 95 % CI: 10–28).</div></div><div><h3>Conclusion</h3><div>This meta-analysis showed the high prevalence of TP53, PIK3CA, and APC mutations among CRC patients, with TP53 mutations being the most common among these three genes.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"298 ","pages":"Pages 198-207"},"PeriodicalIF":2.1,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145362093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of miR-10b-5p in prostate cancer and its exosome-mediated angiogenesis effect","authors":"Jia Wang ,&nbsp;Chuan Zhou ,&nbsp;Qi-dong Wang ,&nbsp;Wen-bo Zhang ,&nbsp;Chao Wang ,&nbsp;Yun-Feng Zhang ,&nbsp;Hao-Xuan Lv ,&nbsp;Feng-Hai Zhou","doi":"10.1016/j.cancergen.2025.08.009","DOIUrl":"10.1016/j.cancergen.2025.08.009","url":null,"abstract":"<div><h3>Objective</h3><div>Prostate cancer (PCa) continues to be a major cause of cancer-related mortality globally, underscoring the critical need for novel therapeutic strategies. This study investigates the oncogenic function of miR-10b-5p in PCa progression and evaluates its potential as both a diagnostic marker and therapeutic target.</div></div><div><h3>Methods</h3><div>miR-10b-5p was initially identified as a candidate oncogene through bioinformatic analysis of The Cancer Genome Atlas (TCGA) PCa data, followed by validation of its expression levels in clinical PCa specimens via fluorescence in situ hybridization (FISH). Functional assays (proliferation, migration, invasion) were performed to assess the impact of miR-10b-5p on PCa cell behavior. The tumor suppressor ZMYND11 was confirmed as a direct target of miR-10b-5p using dual-luciferase reporter assays. The pro-angiogenic capacity of PCa-derived exosomes harboring miR-10b-5p was evaluated using in vitro endothelial tube formation assays and in vivo mouse models.</div></div><div><h3>Results</h3><div>miR-10b-5p expression was significantly elevated in PCa tissues and cell lines, and its levels correlated with aggressive tumor features. Mechanistically, miR-10b-5p directly suppressed ZMYND11 expression, thereby promoting PCa cell proliferation, migration, and invasion. Crucially, exosomes derived from miR-10b-5p-expressing PCa cells exhibited potent pro-angiogenic activity, significantly enhancing endothelial tube formation in vitro and stimulating tumor neovascularization in vivo.</div></div><div><h3>Conclusion</h3><div>This study demonstrates that miR-10b-5p promotes prostate cancer progression by targeting ZMYND11, while its exosomes additionally exhibit pro-angiogenic effects, providing a novel therapeutic target for clinical intervention.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"298 ","pages":"Pages 27-38"},"PeriodicalIF":2.1,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144926173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of extracellular vesicles on breast cancer metastasis and therapeutics: genetic considerations","authors":"Leila Jahangiri","doi":"10.1016/j.cancergen.2025.08.003","DOIUrl":"10.1016/j.cancergen.2025.08.003","url":null,"abstract":"<div><div>Breast cancer is a significant health problem across the world, and a better understanding of the cellular and molecular properties of the microenvironment in which the breast cancer cells reside is paramount. Breast cancer cells exhibit an intricate bilateral interaction with the tumour microenvironment, which can contribute to tumour progression. This tumour microenvironment comprises a host of proteins, proteoglycans, glycoproteins, signalling molecules, stromal and immune cells, in addition to extracellular vesicles. Extracellular vesicles encompass a range of vesicles that facilitate cell-to-cell communication and signal relay. Examples of these extracellular vesicles include microvesicles, exosomes and apoptotic bodies. Other categorisations divide extracellular vesicles into exosomes and ectosomes based on their biogenesis. The content of extracellular vesicles can be DNA, RNA, miRNA, proteins, glycans and lipids. This content can affect the tumour microenvironment and tumour metastasis and progression. As such, this review article aims to understand the content of extracellular vesicles and those that promote invasion and metastasis in the context of the tumour microenvironment. The implications of these extracellular vesicles for breast cancer therapeutics will be addressed. Finally, the genes indicated in these processes will be discussed.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"298 ","pages":"Pages 1-9"},"PeriodicalIF":2.1,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144841528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and multi-cohort validation of a prognostic risk score model for oral squamous cell carcinoma based on a three-gene signature","authors":"Junxu Chen ,&nbsp;Dongwook Kim ,&nbsp;Jae Young Kim ,&nbsp;Hyung Jun Kim","doi":"10.1016/j.cancergen.2025.09.005","DOIUrl":"10.1016/j.cancergen.2025.09.005","url":null,"abstract":"<div><h3>Background</h3><div>Oral squamous cell carcinoma (OSCC) carries substantial mortality despite surgery-based management. Reliable biomarkers and practical prognostic tools are needed to guide individualized care.</div></div><div><h3>Methods</h3><div>Transcriptomic and clinical data from TCGA and multiple GEO cohorts were integrated. Candidate genes identified by differential expression analysis, WGCNA, and PPI were refined using LASSO and Random Forest, then entered a multivariable Cox model to derive a three-gene risk score. Performance was assessed with Kaplan–Meier curves, time-dependent ROC, and calibration, and validated across internal, external, and combined datasets. Expression was examined by RT-qPCR and Western blot in OSCC and normal oral cell lines. Immune infiltration and pathway enrichment analyses were conducted to contextualize biology.</div></div><div><h3>Results</h3><div>The three-gene signature (<em>CXCL12, PLAU, PXDN</em>) separated risk groups in the training cohort with 1/3/5-year AUCs of 0.767/0.625/0.714. In three independent external cohorts, high-risk patients consistently had worse overall survival (log-rank <em>p</em> = 0.0092, ≤0.0001, ≤0.0001), with time-AUC ranges of 0.581–0.747 (1-year), 0.555–0.795 (3-year), and 0.603–0.812 (5-year). In TCGA, the score remained prognostic across sex, age, smoking, drinking, and stage III/IV subgroups (all <em>p</em> ≤ 0.05), with a consistent trend in stage I/II (<em>p</em> = 0.09). A nomogram integrating clinical variables with the risk score achieved a C-index of 0.63 with good 1–5-year calibration and outperformed TNM staging alone (C-index 0.63 vs 0.58; 95 % CI 0.58–0.70 vs 0.54–0.61). RT-qPCR/Western blot confirmed consistent differential expression of all three biomarkers. Immune-infiltration and pathway analyses revealed distinct microenvironmental and molecular features across risk strata.</div></div><div><h3>Conclusion</h3><div>We present a robust, externally validated three-gene prognostic model for OSCC, supported by experimental evidence and superior to TNM staging for discrimination, offering a practical nomogram for individualized risk estimation from 1 to 5 years.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"298 ","pages":"Pages 88-98"},"PeriodicalIF":2.1,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145048476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA quality challenges in breast cancer samples from three low-middle income African countries: a straightforward protocol for research in cancer genomics","authors":"Mohamad Chkeir ,&nbsp;Freddy Gnangnon ,&nbsp;Patrice Dangbemey ,&nbsp;Gilbert Fassinou ,&nbsp;Sylvain Lacorre ,&nbsp;Maeva Chaumet ,&nbsp;Mahiné Ivanga ,&nbsp;Rosa-Maria Fassinou ,&nbsp;Romulus Takin ,&nbsp;Sidonie Nguizi Ogoula ,&nbsp;Arnaud Agbanlinsou ,&nbsp;Lionel Forestier ,&nbsp;Nathalie Duprat ,&nbsp;Karine Durand ,&nbsp;Alain Chaunavel ,&nbsp;Pierre-Marie Preux ,&nbsp;Tchin Darré ,&nbsp;Edgard Brice Ngoungou ,&nbsp;Dieu donné Gnonlonfoun ,&nbsp;Simon Azonbakin ,&nbsp;Alexis Parenté","doi":"10.1016/j.cancergen.2025.11.005","DOIUrl":"10.1016/j.cancergen.2025.11.005","url":null,"abstract":"<div><div>Sub-Saharan African women often develop breast cancer at a younger age, with a high prevalence of aggressive subtypes such as triple-negative breast cancer and elevated mortality. Genetic factors may underlie these patterns, but African populations remain underrepresented in genomic research. As an initial step toward addressing this gap, we evaluated DNA extracted from formalin-fixed paraffin-embedded (FFPE) breast cancer blocks collected in anatomic pathology laboratories in Gabon, Togo, and Benin. Although DNA could be successfully extracted, its functional quality was significantly impaired. Quantitative PCR revealed progressive degradation, with poor amplification efficiency for larger fragments, and next-generation sequencing (NGS) libraries exhibited degraded electropherogram profiles, low coverage, and elevated duplication rates. These limitations likely stem from socio-economic constraints, including delayed processing and prolonged formalin fixation, which promote nucleic acid fragmentation and crosslinking. To overcome these barriers, we established a preservation protocol adapted to the resource and infrastructural limitations of the region: storage of biopsies in physiological saline at –20 °C. This method requires only basic equipment widely available in local hospitals, yet yielded DNA of high integrity, enabled efficient library construction, and produced significantly superior NGS performance compared with FFPE-derived DNA. This cost-effective and scalable approach provides a feasible solution for genomic research in resource-limited settings. Future efforts should focus on complementary strategies for RNA preservation and tumor enrichment to enable comprehensive molecular profiling and advance precision oncology in West Africa.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"298 ","pages":"Pages 295-301"},"PeriodicalIF":2.1,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145568681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “RNF121 Promotes the Proliferation, Migration, and Invasion of Non-Small-Cell lung cancer cell lines” [Cancer Genetics 298-299 (2025) 193-197]","authors":"Jun Jiang ,&nbsp;Xiaoshuai Chen ,&nbsp;Xinjie Dong ,&nbsp;Yanfang Wang ,&nbsp;Jixuan Liu ,&nbsp;Ting Liu ,&nbsp;Xiaolei Bian ,&nbsp;Ming Li ,&nbsp;Yafang Liu","doi":"10.1016/j.cancergen.2025.10.100","DOIUrl":"10.1016/j.cancergen.2025.10.100","url":null,"abstract":"","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"298 ","pages":"Page 226"},"PeriodicalIF":2.1,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145439257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ellagic acid inhibits EZH2: a potential epigenetic therapeutic molecule for cancer","authors":"Kirankumar Nalla ,&nbsp;Biji Chatterjee ,&nbsp;Jagadeesha Poyya ,&nbsp;Aishwarya Swain ,&nbsp;Krishna Ghosh ,&nbsp;Archana Pan ,&nbsp;Chandrashekhar G Joshi ,&nbsp;Bramanandam Manavathi ,&nbsp;Santosh R Kanade","doi":"10.1016/j.cancergen.2025.09.001","DOIUrl":"10.1016/j.cancergen.2025.09.001","url":null,"abstract":"<div><h3>Background</h3><div>Dysregulation of epigenetic processes, characterized by aberrant DNA methylation patterns and histone modifications, is a hallmark of cancer, driving its initiation, progression, and metastasis by silencing tumor suppressor genes or activating oncogenes. Perturbations in histone modifications such as H3K27me3 by EZH2 (Enhancer of Zeste homolog 2) play significant roles in these epigenetic alterations, disrupting normal gene expression and facilitating oncogene activation while suppressing tumor suppressor genes. Consequently, inhibitors targeting enzymes involved in DNA methylation, histone modification, or chromatin remodeling, such as PRC (Polycomb Repressive Complex) complexes, are promising anti-cancer agents, with several undergoing pre-clinical and clinical trials.</div></div><div><h3>Study Design/ Methods</h3><div>The molecular interaction of ellagic acid (EA) with EZH2 was determined by molecular docking using the Schrödinger suite. The binding of EA with EHZ2 was determined by Surface Plasmon Resonance and molecular dynamic simulation studies. In vitro methylation followed by ELISA confirmed the inhibitory potential. Effect of -EA- on the growth and proliferation of the cancer cell lines were determined using the MTT assay. The Ethidium Bromide &amp; Acridine Orange (EB/AO) double staining, colony formation assay, cell cycle and apoptosis assays demonstrated the effect of EA. In vivo mouse xenografts revealed the anticancer potential of EA.</div></div><div><h3>Results</h3><div>Screening of a phytochemical library revealed EA as an effective inhibitor of EZH2. EA interacts strongly with the EZH2, binding to its active sites through π-cation interactions and hydrogen bonds. Molecular dynamic simulation and Surface Plasmon Resonance studies confirmed potent binding affinities of EA, with KD values of 3.28E-06. <em>In-vitro</em> assays validated inhibitory effects on EZH2 by reducing the H3K27me3 levels and induction of autophagy and apoptosis. <em>In- vivo</em> studies using mouse xenografts further demonstrated significant tumor size reductions upon oral administration of EA, with decreased expression of the proliferative marker Ki67 and histone repressive marks.</div></div><div><h3>Conclusion</h3><div>Taken together we showed that inhibition of EZH2 by EA could be used to develop breast cancer therapeutic drug.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"298 ","pages":"Pages 99-112"},"PeriodicalIF":2.1,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145048475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study on the anticancer mechanism of hydroxygenkwanin in esophageal cancer via the ESRRA signaling pathway","authors":"Yuan Wang ,&nbsp;Xin Wan ,&nbsp;Yutian Zhang ,&nbsp;Jia Qi ,&nbsp;Chao Li ,&nbsp;Xiaonan Cui","doi":"10.1016/j.cancergen.2025.09.011","DOIUrl":"10.1016/j.cancergen.2025.09.011","url":null,"abstract":"<div><h3>Objective</h3><div>To explore the role of ESRRA in esophageal squamous cell carcinoma (ESCC) progression and evaluate the antitumor effects of hydroxygenkwanin (HGK), focusing on its interaction with ESRRA and the underlying molecular mechanisms.</div></div><div><h3>Methods</h3><div>Cell viability, apoptosis, invasion, and proliferation were assessed in EC109 and TE-1 cells treated with HGK using CCK-8, Hoechst staining, Transwell, and colony formation assays. ESRRA expression was analyzed via qPCR and Western blot. An ESCC mouse model was established, with treatment groups receiving HGK. Serum IL-10 and IL-12 levels were measured by ELISA; tumor growth and toxicity were evaluated by histology. EMT marker expression was analyzed by IHC and RT-qPCR. TCGA database analysis explored ESRRA-related pathways and its link to the tumor microenvironment and patient survival.</div></div><div><h3>Results</h3><div>HGK inhibited EC109 and TE-1 cell proliferation and migration, especially in EC109 cells, by downregulating ESRRA in a dose-dependent manner. In vivo, HGK reduced tumor growth with minimal toxicity, though high doses showed possible renal effects. IL-12 levels decreased, and EMT markers were altered. ESRRA was overexpressed in ESCC tissues and correlated with EMT-related genes. TCGA analysis confirmed ESRRA’s association with poor survival in ESCC patients.</div></div><div><h3>Conclusion</h3><div>HGK effectively suppresses ESCC with low toxicity, primarily by inhibiting ESRRA and blocking EMT, highlighting its therapeutic potential.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"298 ","pages":"Pages 180-192"},"PeriodicalIF":2.1,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145304175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}