Discover. Oncology最新文献

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The role and diagnostic value of deregulated miRNAs in cervical cancer. 失调控mirna在宫颈癌中的作用及诊断价值。
IF 2.8 4区 医学
Discover. Oncology Pub Date : 2025-05-25 DOI: 10.1007/s12672-025-02744-4
Masoumeh Parvizi, Maryam Vaezi, Farhad Jeddi, Masoumeh Bakhshandeh, Reza Eghdam-Zamiri, Noushin Mobaraki-Asl, Ebrahim Esmati, Abbas Karimi
{"title":"The role and diagnostic value of deregulated miRNAs in cervical cancer.","authors":"Masoumeh Parvizi, Maryam Vaezi, Farhad Jeddi, Masoumeh Bakhshandeh, Reza Eghdam-Zamiri, Noushin Mobaraki-Asl, Ebrahim Esmati, Abbas Karimi","doi":"10.1007/s12672-025-02744-4","DOIUrl":"10.1007/s12672-025-02744-4","url":null,"abstract":"<p><p>Cervical cancer (CC) remains a significant global health concern, particularly affecting women in low-income countries. Despite advancements in screening programs, CC continues to pose a substantial mortality risk, highlighting the need to explore diagnostic and treatment modalities. This review focuses on the role of deregulated microRNAs (miRNAs) in CC development, emphasizing their potential as biomarkers for early detection and prognosis in body fluids. miRNAs have emerged as critical regulators of key cellular processes, including proliferation, migration, invasion, and apoptosis, and their dysregulation is closely linked to CC progression. Upregulated miRNAs such as miR-146b-3p, miR-1908, and miR-21 promote CC progression by targeting tumor suppressor genes, while downregulated miRNAs like miR-23-3p and miR-4262 are associated with reduced tumor aggressiveness. miRNAs also hold significant promise as non-invasive prognostic biomarkers. Their expression levels correlate with clinical outcomes, including tumor stage, metastasis, and overall survival, making them valuable tools for risk stratification and personalized treatment strategies. Liquid biopsies, which detect circulating miRNAs in bodily fluids, offer a minimally invasive approach to monitor tumor dynamics and predict patient outcomes. Furthermore, exosomal miRNAs are emerging as promising diagnostic and prognostic tools for CC. Advanced diagnostic technologies and bioinformatics tools are anticipated to enhance the identification of evident miRNA biomarkers in the clinical settings. Standardized protocols for sample collection and analysis will improve the reproducibility of miRNA studies, while a deeper understanding of miRNA biology may unlock their potential as therapeutic targets. In conclusion, this review consolidates current research on deregulated miRNAs in CC, highlighting their diagnostic and prognostic significance. The findings underscore the potential of miRNAs to revolutionize CC management through innovative diagnostic and therapeutic strategies.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"922"},"PeriodicalIF":2.8,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12104134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Identification of key ferroptosis genes in hepatocellular carcinoma and type 2 diabetes mellitus through bioinformatics analysis. 通过生物信息学分析鉴定肝癌和2型糖尿病关键铁下垂基因。
IF 2.8 4区 医学
Discover. Oncology Pub Date : 2025-05-25 DOI: 10.1007/s12672-025-02758-y
Jinjin Zhou, Yage Shi, Yulun Jian, Yuhan Li, Wenya Yu, Wei Mu, Yang Ge
{"title":"Identification of key ferroptosis genes in hepatocellular carcinoma and type 2 diabetes mellitus through bioinformatics analysis.","authors":"Jinjin Zhou, Yage Shi, Yulun Jian, Yuhan Li, Wenya Yu, Wei Mu, Yang Ge","doi":"10.1007/s12672-025-02758-y","DOIUrl":"10.1007/s12672-025-02758-y","url":null,"abstract":"<p><p>Ferroptosis is a programmed cell death mode associated with iron metabolism, with accumulation of intracellular lipid peroxides, which is closely related to the occurrence and development of multiple diseases, including type 2 diabetes mellitus (T2DM) and hepatocellular carcinoma (HCC). T2DM is a chronic metabolic disorder characterized by a combination of impaired insulin sensitivity and insufficient insulin production, frequently accompanied by obesity and fatty liver, which increases the risk of developing HCC. To explore the complex interactions between ferritin deposition, T2DM, and HCC, we performed bioinformatics analysis on publicly available gene expression data and identified 23 differentially expressed genes (DEGs) that are commonly expressed in both T2DM and HCC. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that these DEGs are primarily enriched in fatty acid metabolism and ferroptosis pathways. The weighted gene co-expression network analysis (WGCNA) identified 6 key genes associated with the pathogenesis of both diseases. Taking the intersection of DEGs and iron deposition-related genes, we identified ACSL4 as a key ferroptosis gene involved in the co-morbidity of T2DM and HCC. To validate the bioinformatics findings, we assessed the expression of ACSL4 using Receiver operating characteristic (ROC) curve analysis, which revealed an Area Under the Curve (AUC) of 0.886 for HCC and 0.745 for T2DM. Additionally, an insulin resistance model was established in HepG2 cells by treatment with 350 µM palmitic acid (PA), resulting in significant changes in cell morphology. Oil Red O staining showed a marked increase in lipid accumulation. RT-PCR analysis further confirmed the significant alteration in ACSL4 gene expression. In conclusion, this study is the first to integrate bioinformatics tools to investigate the potential mechanistic links between iron metabolism and the comorbidity of T2DM and HCC, uncovering a novel pathogenic pathway. These findings provide new directions for drug development and therapeutic strategies in the future.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"916"},"PeriodicalIF":2.8,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12104123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
GTV delineating for patients with postoperative glioma based on enhanced T2-FLAIR sequence instead of enhanced T1-TFE sequence: a feasibility study. 基于增强T2-FLAIR序列代替增强T1-TFE序列对术后胶质瘤患者进行GTV划定的可行性研究
IF 2.8 4区 医学
Discover. Oncology Pub Date : 2025-05-25 DOI: 10.1007/s12672-025-02697-8
Yuanyuan Li, Qingqing Yuan, Hengbing Jiang, Yin Zhang, Xingru Sun
{"title":"GTV delineating for patients with postoperative glioma based on enhanced T2-FLAIR sequence instead of enhanced T1-TFE sequence: a feasibility study.","authors":"Yuanyuan Li, Qingqing Yuan, Hengbing Jiang, Yin Zhang, Xingru Sun","doi":"10.1007/s12672-025-02697-8","DOIUrl":"10.1007/s12672-025-02697-8","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the comparison of MRI Enhanced T2-Fluid Attenuated Inversion Recovery(T2-FLAIR+C) sequence and Enhanced T1-Turbo Field Echo(T1-TFE+C) sequence in delineating Gross Tumor Volume (GTV) of postoperative glioma.</p><p><strong>Method: </strong>Twenty patients with postoperative glioma underwent MRI simulation(MRI-sim) were enrolled. The T1-TFE+C sequence and T2-FLAIR+C sequence were separately registered with CT simulation(CT-sim). GTV was delineated by the same physician based on CT/T1 and CT/T2, respectively. Subsequently, the number, volume and overlapping ratio(OR) of GTV between the two groups were quantified and analyzed statistically. The signal intensity(SI) of the tumor area, normal gray matter and white matter (background of normal brain tissue)were measured on T1-TFE+C and T2-FLAIR+C sequences, respectively. The contrast ratio(CR) of the tumor in the two sequences were calculated and statistically analyzed.</p><p><strong>Results: </strong>The volumes of GTV delineated based on CT/T1 and CT/T2 were (55.89 ± 30.20) cm<sup>3</sup> and (56.75 ± 30.52) cm<sup>3</sup>, respectively. There was no statistically significance between the two groups of GTV volumes (P > 0.05). The maximum OR, minimum OR and average OR of GTV volumes between the two groups were 99.77%, 86.90%, and 94.51%, respectively. The CR of tumor/white matter and tumor/gray matter in T2-FLAIR+C were significantly higher than those in the T1-TFE+C sequence (P < 0.05).</p><p><strong>Conclusion: </strong>The volume of GTV delineated by T2-FLAIR+C was slightly larger compared to that by T1-TFE+C, and T2-FLAIR+C could provide a more comprehensive range of GTV delineation. CR was statistically significant between the two groups (P < 0.05), and T2-FLAIR+C demonstrated the ability to accurately depict changes in tumor boundaries and surrounding edema with a higher tumor enhancement signal. Therefore, GTV delineation of gliomas based on T2-FLAIR+C may offer certain advantages and could potentially serve as a complete replacement for T1-TFE+C in future clinical applications.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"919"},"PeriodicalIF":2.8,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12104131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Bladder cancer biomarker analysis and drugtarget prediction based on pyroptosis-related genes. 基于焦热相关基因的膀胱癌生物标志物分析及药物靶标预测。
IF 2.8 4区 医学
Discover. Oncology Pub Date : 2025-05-25 DOI: 10.1007/s12672-025-02754-2
Ping Li, Xuexi Yang, Qin Liu, Hanchao Zhang, Zhumei Luo
{"title":"Bladder cancer biomarker analysis and drugtarget prediction based on pyroptosis-related genes.","authors":"Ping Li, Xuexi Yang, Qin Liu, Hanchao Zhang, Zhumei Luo","doi":"10.1007/s12672-025-02754-2","DOIUrl":"10.1007/s12672-025-02754-2","url":null,"abstract":"<p><strong>Background: </strong>Bladder cancer (BC) is a common and lethal condition that presents a considerable risk to public health. Studies have demonstrated that inflammation is pivotal in the onset and advancement of BC. Pyroptosis is a type of programmed cell death distinguished by inflammatory reactions associated with innate immunity. Inhibiting inflammatory cytokine production and modulating pyroptosis-related pathways may provide a potential treatment approach for BC. We predicted and validated the Pyroptosis-related genes and potential biomarkers associated with BC, ultimately predicting therapeutic drugs based on the hub gene targets.</p><p><strong>Methods: </strong>The gene expression profiles for BC were acquired from the Gene Expression Omnibus (GEO) database. Bioinformatics analysis identified gene expression differences associated with pyroptosis in BC. The differently regulated pyroptosis-related genes were validated, and enrichment studies of specific biological processes and associated signaling pathways in BC were performed. Immune infiltration analysis and single-cell analysis were conducted to clarify the immune infiltration characteristics in BC. Therapeutic agents were forecasted based on critical gene targets.</p><p><strong>Results: </strong>In BC, 27 differentially expressed pyroptosis-related genes were discovered, with CASP8, NLRP3, CASP3, IL18, TP53, GSDME, IL1A, PYCARD, CYCS, and CASP9 recognized as key genes. Enrichment analysis revealed that the occurrence of pyroptosis was primarily associated with inflammation, activation of immune responses, and apoptosis. Additionally, data validation demonstrated that CASP8, NLRP3, CASP3, IL18, TP53, CYCS, and CASP9 were involved in the regulation of pyroptosis. The results of immune infiltration and single-cell analyses further validated that B-cells-memory, T-cells_CD8, T-cells_follicular-helper, Macrophages-M1, Dendritic_cells_activated, and Mast_cells_resting play significant roles in the immune processes of BC. The drug targeting predictions for pivotal genes identified Triethyl phosphate, Regorafenib, Ponatinib, Lenvatinib, Nintedanib, and Quercetin as potential key drugs or compounds for the treatment of BC.</p><p><strong>Conclusion: </strong>This study elucidated the relationship between the development of BC and mechanisms of cellular senescence, apoptosis, and immunity. It clarified the roles of 27 genes associated with cellular senescence in BC and predicted that Triethyl phosphate, Regorafenib, Ponatinib, Lenvatinib, Nintedanib, and Quercetin may be key drugs or compounds for the treatment of BC.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"924"},"PeriodicalIF":2.8,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12104127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Reciprocal regulation between m6 A modifications and non-coding RNAs: emerging roles in cancer therapeutic resistance. m6 A修饰和非编码rna之间的相互调控:在癌症治疗耐药中的新作用。
IF 2.8 4区 医学
Discover. Oncology Pub Date : 2025-05-25 DOI: 10.1007/s12672-025-02641-w
Dan Fan, Yan Shang, Yating Cong, Yanlin Jiao, Na Li, Hailong Zhao
{"title":"Reciprocal regulation between m6 A modifications and non-coding RNAs: emerging roles in cancer therapeutic resistance.","authors":"Dan Fan, Yan Shang, Yating Cong, Yanlin Jiao, Na Li, Hailong Zhao","doi":"10.1007/s12672-025-02641-w","DOIUrl":"10.1007/s12672-025-02641-w","url":null,"abstract":"<p><p>In recent years, the interplay between N6-methyladenosine (m<sup>6</sup>A) modifications and non-coding RNAs (ncRNAs) has emerged as a pivotal research area, owing to their crucial involvement in the pathophysiological mechanisms underlying various diseases. A significant hurdle in cancer therapy is therapeutic resistance, which frequently contributes to adverse patient outcomes. Recent investigations have underscored the vital role that interactions between m<sup>6</sup>A modifications and ncRNAs play in mediating cancer therapeutic resistance via the MAPK, PI3K/Akt/mTOR, Wnt/β-catenin, HIPPO, and NF-κB pathways. This review elucidates how these interactions drive tumor therapeutic resistance by modulating these pathways. By dissecting the regulatory dynamics between m<sup>6</sup>A and ncRNAs in the context of cancer therapeutic resistance, this review aims to deepen the understanding of m6A-ncRNA interaction in cancer therapeutic resistance and identify potential therapeutic targets to improve cancer treatment efficacy.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"920"},"PeriodicalIF":2.8,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12104133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Leveraging multiple cell-death patterns based on machine learning to decipher the prognosis, immune, and immune therapeutic response of soft tissue sarcoma. 利用基于机器学习的多种细胞死亡模式来解读软组织肉瘤的预后、免疫和免疫治疗反应。
IF 2.8 4区 医学
Discover. Oncology Pub Date : 2025-05-25 DOI: 10.1007/s12672-025-02587-z
Binfeng Liu, Shasha He, Chenbei Li, Zijian Xiong, Zhaoqi Li, Chengyao Feng, Hua Wang, Chao Tu, Zhihong Li
{"title":"Leveraging multiple cell-death patterns based on machine learning to decipher the prognosis, immune, and immune therapeutic response of soft tissue sarcoma.","authors":"Binfeng Liu, Shasha He, Chenbei Li, Zijian Xiong, Zhaoqi Li, Chengyao Feng, Hua Wang, Chao Tu, Zhihong Li","doi":"10.1007/s12672-025-02587-z","DOIUrl":"10.1007/s12672-025-02587-z","url":null,"abstract":"<p><p>Soft tissue sarcomas (STS) imposes a substantial healthcare burden on society. The progression of these tumors is significantly influenced by diverse modes of programmed cell death (PCD), which can serve as valuable indicators for assessing prognosis and immune therapeutic response in STS. Nonetheless, the precise role of multiple cell death patterns in STS is yet to be clarified. We employed 96 machine-learning algorithm combination frameworks to identify novel cell death-related signatures (CDSigs) with the highest mean c-index, indicating their excellence. The independence test and comparison with previously published models further confirmed the stability and quality of these signatures for survival prediction in STS. The nomogram, comprising the cell death score (CDS) and clinical features, exhibited excellent predictive performance. Additionally, the CDSigs revealed associations with immune checkpoint genes and the immune microenvironment in STS. Furthermore, the results demonstrated that patients with lower CDS had the potential for greater benefit from immune therapeutic responses compared to those with higher CDS. Moreover, STS patients with low-risk scores exhibited heightened sensitivity to doxorubicin, axitinib, cisplatin, and camptothecin. Finally, the RT-qPCR results underscored significant differences in expression levels of several CDSigs genes between STS and normal cells. Overall, we comprehensively analyzed the multiple PCD in STS and established a novel CDSig for STS patients. This novel CDSig holds great promise in deciphering the prognosis, immune, and immune therapeutic response of STS.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"917"},"PeriodicalIF":2.8,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12104128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Prognostic and therapeutic insights from lactate metabolism and tumor immune microenvironment in head and neck squamous cell carcinoma. 乳酸代谢和肿瘤免疫微环境对头颈部鳞状细胞癌预后和治疗的影响。
IF 2.8 4区 医学
Discover. Oncology Pub Date : 2025-05-24 DOI: 10.1007/s12672-025-02706-w
Huanyu Jiang, Lijuan Zhou, Haidong Zhang, Shanchun Gong, Zhenkun Yu
{"title":"Prognostic and therapeutic insights from lactate metabolism and tumor immune microenvironment in head and neck squamous cell carcinoma.","authors":"Huanyu Jiang, Lijuan Zhou, Haidong Zhang, Shanchun Gong, Zhenkun Yu","doi":"10.1007/s12672-025-02706-w","DOIUrl":"10.1007/s12672-025-02706-w","url":null,"abstract":"<p><p>Head and neck squamous cell carcinoma (HNSCC) exhibits a poor prognosis, particularly in advanced stages characterized by high recurrence and metastasis rates. This study investigates the role of lactate metabolism in HNSCC, aiming to develop a prognostic model to predict immunotherapy outcomes. Genomic and clinical data from The Cancer Genome Atlas and Gene Expression Omnibus databases were analyzed, focusing on 233 lactate metabolism-related genes (LMGs). Differential expression and Cox regression analyses identified two significant prognostic genes: glycogen phosphorylase L (PYGL) and solute carrier family 16 member 3 (SLC16 A3, encoding MCT4). A lactate risk score (LRS) model constructed from these genes demonstrated robust predictive accuracy across multiple validation datasets. Multivariate analysis validated LRS as an independent prognostic factor, and a nomogram integrating LRS with clinical parameters further improved survival prediction accuracy. Immune infiltration analyses revealed distinct immune landscapes between high- and low-risk groups. Elevated levels of CD4 naïve T cells, resting NK cells, M0 macrophages, and activated mast cells characterized the high-risk group, whereas naive B cells, plasma cells, CD8 T cells, T follicular helper cells, regulatory T cells, gamma delta T cells, resting dendritic cells, resting mast cells, and eosinophils predominated in the low-risk group. Additionally, molecular docking suggested valproic acid as a potential inhibitor of MCT4. Immunohistochemical analyses showed increased PYGL and MCT4 expression correlated with advanced tumor stage, alongside decreased expression of CXCL9 and CXCL10. These findings highlight the critical role of lactate metabolism in HNSCC progression and immunotherapy resistance, identifying PYGL and MCT4 as promising therapeutic targets.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"909"},"PeriodicalIF":2.8,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144136125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Genomic and clinical insights into ovarian cancer: subtype-specific alterations and predictors of metastasis and relapse. 卵巢癌的基因组和临床见解:亚型特异性改变和转移和复发的预测因子。
IF 2.8 4区 医学
Discover. Oncology Pub Date : 2025-05-24 DOI: 10.1007/s12672-025-02725-7
Feng Cheng, Feng Shao, Yiping Tian, Shujun Chen
{"title":"Genomic and clinical insights into ovarian cancer: subtype-specific alterations and predictors of metastasis and relapse.","authors":"Feng Cheng, Feng Shao, Yiping Tian, Shujun Chen","doi":"10.1007/s12672-025-02725-7","DOIUrl":"10.1007/s12672-025-02725-7","url":null,"abstract":"<p><p>Ovarian cancer exhibits marked molecular heterogeneity and variable clinical outcomes. Understanding genomic alterations associated with metastasis and relapses may guide personalized management, particularly in high-grade serous carcinoma (HGSC). We performed targeted sequencing of 1021 cancer-related genes in tumor-normal pairs from 99 treatment-naïve ovarian cancer patients. Associations between copy number variations (CNVs), metastatic patterns, tumor mutation burden (TMB), and relapses were assessed. Analyses of relapse predictors were restricted to HGSC patients. Statistical significance was determined with Bonferroni correction for multiple comparisons. TP53 mutations were frequent in HGSC (96.6%), whereas PIK3CA, ARID1A, and ATRX mutations were enriched in non-HGSC tumors. FLT3, CDH23, and EPAS1 mutations were associated with metastasis. TMB-high tumors (≥ 9 mutations/Mb) showed distinct profiles, including SMARCA4 and FUBP1 mutations and CNV gains in CEBPA. Among HGSC patients, TBX3 mutations were exclusively observed in those relapsing within six months (p = 0.028), while ARID1B, MAP2K1, and FLT4 were enriched in relapse groups. After neoadjuvant chemotherapy and FIGO stage IV were also associated with relapses. This study reveals subtype-specific and metastasis-related genomic alterations in ovarian cancer and identifies potential relapse-associated mutations in HGSC. While exploring, these findings support further investigation into individualized risk stratification and biomarker-driven therapeutic strategies.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"907"},"PeriodicalIF":2.8,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144136102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unraveling the significance of cuproptosis in hepatocellular carcinoma heterogeneity and tumor microenvironment through integrated single-cell sequencing and machine learning approaches. 通过整合单细胞测序和机器学习方法揭示铜增生在肝细胞癌异质性和肿瘤微环境中的意义。
IF 2.8 4区 医学
Discover. Oncology Pub Date : 2025-05-24 DOI: 10.1007/s12672-025-02696-9
Wang Liu, Liangjing Xia, Yuan Peng, Qiang Cao, Ke Xu, Huiyan Luo, Yongjun Peng, Yanping Zhang
{"title":"Unraveling the significance of cuproptosis in hepatocellular carcinoma heterogeneity and tumor microenvironment through integrated single-cell sequencing and machine learning approaches.","authors":"Wang Liu, Liangjing Xia, Yuan Peng, Qiang Cao, Ke Xu, Huiyan Luo, Yongjun Peng, Yanping Zhang","doi":"10.1007/s12672-025-02696-9","DOIUrl":"10.1007/s12672-025-02696-9","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Hepatocellular carcinoma (HCC) exhibits pronounced heterogeneity, which significantly limits the effectiveness of precision therapies. A comprehensive understanding of the biological characteristics and molecular mechanisms underlying HCC cell subpopulations is crucial for improving prognostic predictions and refining treatment strategies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Single-cell RNA sequencing data were obtained from the GEO database and processed using the Seurat R package for quality control, including data filtering, batch effect correction, and dimensionality reduction via PCA and UMAP to visualize cell distribution and identify distinct subpopulations. Cell types were annotated using established marker genes and literature references. The GSVA method was applied to evaluate the activity of 18 programmed cell death pathways. Cell developmental trajectories were reconstructed using Monocle 2 and validated with cytoTRACE to assess differentiation potential. Metabolic pathway activity was analyzed using the scMetabolism package. Bulk RNA sequencing data from the TCGA cohort were integrated to identify prognosis-associated genes through univariate Cox regression. The malignant potential of tumor subpopulations was quantified using GSVA scoring. Weighted gene co-expression network analysis (WGCNA) was employed to identify cuproptosis-related genes. A risk scoring model was constructed using LASSO regression and multivariate Cox regression based on cuproptosis-related genes and marker genes of cuproptosis-characterized tumor cells. The model's performance was validated across TCGA, GEO, and ICGC datasets. Additionally, the relationships between risk scores, clinical characteristics, key signaling pathways, and immunotherapy responses were explored. Finally, a prognostic nomogram was developed to support clinical decision-making.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;12 programmed cell death pathways were enriched in tumors, with cuproptosis defining HCC, particularly in the C2 subpopulation. GSVA highlighted high-risk patient enrichment in proliferation, DNA repair, and metabolism, reflecting aggressive malignancy. Developmental trajectory and metabolic analyses confirmed greater stemness and metabolic activity in C2. TCGA linked cuproptosis-related subpopulations to poor prognosis. The risk model stratified patients (validated in TCGA/GEO/ICGC), correlating with clinical grade, T-stage, survival (HR = 2.597, 95%CI 2.051-3.289, P &lt; 0.05). The nomogram showed strong predictive power (C-index = 0.716), aiding clinical decisions.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;The C2 subpopulation represents the most malignant subset of HCC cells, with cuproptosis serving as a defining characteristic of this subgroup. The risk scoring and nomogram models based on cuproptosis-related genes offer novel insights and a robust scientific foundation for prognostic prediction and personalized treatment in HCC patients. These findings highlig","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"900"},"PeriodicalIF":2.8,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144136131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Endoscopic thyroidectomy for central lymph node dissection-is there a difference in the number of lymph node dissections performed through different surgical approaches? A retrospective cohort study and pooled data research. 内镜甲状腺切除术治疗中央淋巴结清扫-不同手术入路的淋巴结清扫次数是否有差异?回顾性队列研究和汇总数据研究。
IF 2.8 4区 医学
Discover. Oncology Pub Date : 2025-05-24 DOI: 10.1007/s12672-025-02712-y
Zheng Wang, Han Yan, Jun Yu, Rui Sha, Zhao Cai Yin, Bin Chen, Ya Bing Wang, Chang Sheng Yu
{"title":"Endoscopic thyroidectomy for central lymph node dissection-is there a difference in the number of lymph node dissections performed through different surgical approaches? A retrospective cohort study and pooled data research.","authors":"Zheng Wang, Han Yan, Jun Yu, Rui Sha, Zhao Cai Yin, Bin Chen, Ya Bing Wang, Chang Sheng Yu","doi":"10.1007/s12672-025-02712-y","DOIUrl":"10.1007/s12672-025-02712-y","url":null,"abstract":"<p><strong>Background: </strong>Endoscopic thyroidectomies are commonly performed for thyroid cancer. Previous studies indicated that trans-areola approach is inferior in central lymph node dissection (CLND) due to clavicle protruding. The present study aimed to compare different surgical approaches of endoscopic thyroidectomies regarding surgical outcomes.</p><p><strong>Methods: </strong>Retrospective analysis of 153 patients underwent endoscopic thyroidectomies through oral and areola approaches from Nov. 2019 to Dec. 2022 in our institution, baseline information, surgical outcomes and postoperative complications were recorded and analyzed. For pooled data analysis, comprehensive searching was done to identify studies concerning comparison of endoscopic thyroidectomies. Basic information and surgical outcomes were extracted. RevMan 5.4 was used to analyze the pooled data. p < 0.05 was considered statistically different.</p><p><strong>Results: </strong>A total of 153 patients were included with 75 in oral, 78 in areola. The operative time was longer in oral compared with other two groups. Number of lymph nodes, positive lymph nodes, hospital stay, postoperative drainage and complications were not different between the two groups. For the systematic review, five studies of oral and areola comparisons containing 568 patients was finally included in the meta-analysis. The operative time was slightly longer in oral group. Number of positive lymph nodes were slightly larger in areola. The blood loss, lymph nodes, hospital stay and transient hoarseness were not different between oral and areola.</p><p><strong>Conclusions: </strong>Oral demanded more operative time than other approaches. Lymph nodes, positive lymph nodes and hospital stay were similar between different groups. Areola was comparable with oral in lymph nodes and positive lymph nodes.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"898"},"PeriodicalIF":2.8,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144136072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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